CN110913899A - Hbv疫苗 - Google Patents

Hbv疫苗 Download PDF

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CN110913899A
CN110913899A CN201880028408.6A CN201880028408A CN110913899A CN 110913899 A CN110913899 A CN 110913899A CN 201880028408 A CN201880028408 A CN 201880028408A CN 110913899 A CN110913899 A CN 110913899A
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E·巴恩斯
S·钦纳坎南
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Abstract

本发明涉及一种多HBV免疫原病毒载体疫苗,其包含:包含免疫原表达盒的病毒载体,其中由表达盒编码的蛋白的表达设置为由启动子驱动,其中所述免疫原表达盒编码:a)HBV核心;b)修饰的HBV聚合酶(Pmut),其中所述修饰是对野生型HBV聚合酶的突变以基本上除去聚合酶功能;c)HBV表面抗原(HbsAg);和d)基因间序列,其设置为导致至少HBV表面抗原(HbsAg)表达为与HBV核心和修饰的HBV聚合酶(Pmut)分离的蛋白,其中所述基因间序列在编码HBV核心和修饰的HBV聚合酶(Pmut)的序列的下游(3’)和编码HBV表面抗原(HbsAg)的序列的上游(5’);并且涉及相关的组合物,接种疫苗方法以及治疗或预防HBV感染的方法。

Description

HBV疫苗
技术领域
本发明涉及用于慢性乙型肝炎的治疗性疫苗的病毒载体疫苗的多抗原HBV免疫原。
背景技术
乙型肝炎是一种侵袭肝脏并可能导致急性和慢性疾病两者的病毒感染。乙型肝炎病毒(HBV)通过与感染者的血液或其它体液接触传播。没有针对急性乙型肝炎的特异性治疗。因此,护理旨在保持舒适性和足够的营养平衡,包括补充因呕吐和腹泻而流失的液体。然而,解决急性乙型肝炎的主要方法是通过使用接种疫苗来预防。一旦确定,可以用药物治疗慢性乙型肝炎感染,其包括口服抗病毒剂。治疗可以减缓肝硬化的进程,减少肝癌的发生率并改善长期存活率。然而,一旦确定了慢性感染,自发的病毒控制就很少了。因此,主要目标是开发免疫治疗性HBV疫苗以诱导病毒控制或治愈。
目前,在I期和II期临床试验中几乎没有不同的T细胞诱导疫苗,它们全部基于一种或两种全长HBV抗原或多种截短或全长嵌合HBV抗原或基于HBV蛋白组的合成肽。GlobeImmune公司的GS-4774目前处于II期临床试验中(GS-4774具有热灭活的酵母细胞,其可表达HBx HBsAg和HBcAg的嵌合体)。Transgene公司的TG1050目前处于I期临床试验中(TG1050是一种基于编码三种HBV抗原(核心-聚合酶-包膜)的截短形式嵌合体疫苗的人腺病毒血清型5。Altimmune公司的HepTcellTM目前处于I期临床试验中(HepTcell是一种完全合成的肽产品,基于源自HBV蛋白保守区的9种合成的32-40聚体肽)。Inovio公司的INO-1800目前处于I期临床试验中(INO-1800是一种靶向乙型肝炎病毒分支A和C表面抗原和HBV核心抗原的多抗原
Figure BDA0002251776950000011
DNA免疫疗法)。目前可用的预防性HBV疫苗(通常基于HBV蛋白疫苗)对慢性感染的HBV个体无治疗作用,因此它们无法控制慢性HBV感染。
因此,本发明的目的是提供一种用于HBV感染的改良疫苗。
发明内容
根据本发明的第一方面,提供了一种多HBV免疫原病毒载体疫苗,其包含:
包含免疫原表达盒的病毒载体,其中,由所述表达盒编码的蛋白的表达设置为由启动子驱动,其中,所述免疫原表达盒编码:
a)HBV核心;
b)修饰的HBV聚合酶(Pmut),其中,所述修饰是对野生型HBV聚合酶的突变以基本上除去聚合酶功能;
c)HBV表面抗原(HbsAg);和
d)基因间序列,其设置为导致至少HBV表面抗原(HbsAg)表达为与HBV核心和修饰的HBV聚合酶(Pmut)分离的蛋白,
其中,所述基因间序列在编码HBV核心和修饰的HBV聚合酶(Pmut)的序列的下游(3’)和编码HBV表面抗原(HbsAg)的序列的上游(5’)。
该基因间序列可以包含切割结构域、IRES(内部核糖体进入位点)、剪接信号或次级启动子。在一个实施方式中,该基因间序列包含切割结构域,其包含设置为导致核糖体跳跃的序列。在另一个实施方式中,该基因间序列包含次级启动子以促进至少表面抗原(HbsAg)的表达。
对不同的HBV蛋白诱导强烈的、多抗原特异性的T细胞应答被认为在解决慢性HBV感染的病毒清除中起着重要作用。为了诱导多抗原T细胞应答,重要的是要具有最大数量的T细胞表位,这需要在诱导T细胞的HBV疫苗中编码全长HBV蛋白。目前正在开发的某些HBV疫苗不编码全长HBV抗原。本发明的疫苗可以编码3种全长HBV蛋白(即核心,任选地具有核心前区、聚合酶和表面蛋白)。另外,疫苗设计利用至少两种蛋白表达,例如使用F2A肽切割策略来编码单独的表面蛋白,该蛋白除了诱导T细胞应答外还可以诱导抗体应答,这可能在增强T细胞疫苗的治疗效果中起作用,并可能有助于清除慢性感染个体中的病毒。基于哺乳动物系统(与例如酵母的其它系统相比)的诱导抗体具有提供可以诱导适用于天然宿主的抗体的哺乳动物型糖基化的选择性优势。
本发明有利地提供了一种编码全长多HBV抗原的单一疫苗,该抗原可以诱导广泛的T细胞应答,并且另外还可以诱导针对表面蛋白的抗体。新型HBV免疫原至少涵盖3种全长HBV抗原(即核心、聚合酶和表面),并将它们编码为病毒载体,例如黑猩猩腺病毒和MVA病毒载体。另外,免疫原中的HBV聚合酶蛋白具有使其功能失效的突变,从而避免其参与HBV基因组复制并提高疫苗的安全性。
通过使用肽切割策略,例如通过使用Furin-2A切割序列或次级启动子,转基因盒可以产生至少两种蛋白,即融合的核心和聚合酶蛋白以及单独的表面蛋白,两者均产生T细胞免疫应答。除了产生T细胞免疫应答外,编码的表面蛋白还可以产生抗体应答。
免疫原表达盒
技术人员将认识到切割结构域可能不会在所有情况下都导致切割,例如,基于F2A的核糖体跳跃事件可能会在小部分的表达中发生,从而使所制得的小部分蛋白将是所有HBV蛋白/抗原的融合体,否则它们会通过切割被分离。因此,在一个实施方式中,免疫原表达盒可以进一步编码至少包含HBV核心、修饰的HBV聚合酶(Pmut)和HBV表面抗原的融合蛋白。
在一个实施方式中,该免疫原表达盒进一步编码HBV前核心(PreC)。在另一个实施方式中,该免疫原表达盒进一步编码HBV PreS1和/或其截短形式。在另一个实施方式中,该免疫原表达盒进一步编码HBV PreS2。
在一个实施方式中,该免疫原表达盒进一步编码HBV前核心(PreC)和HBV PreS1或截短形式的HBV PreS1。在另一个实施方式中,该免疫原表达盒进一步编码HBV前核心(PreC)和HBV PreS2。在一个实施方式中,该免疫原表达盒进一步编码HBV前核心(PreC)和HBV PreS1以及截短形式的PreS1。在一个实施方式中,该免疫原表达盒进一步编码HBV前核心(PreC)、HBV PreS1和/或其截短形式以及HBV PreS2。
在其中编码HBV前核心和核心的实施方式中,免疫原表达盒能够表达HBVe-抗原。本领域技术人员将认识到,HBV e-抗原包含前核心的10个C末端氨基酸和核心的149个N末端氨基酸、或由其组成。为了表达HBV e-抗原,前核心和核心一起表达,并且整个表达的蛋白经历N末端和C末端切割。
在一个实施方式中,HBV核心和修饰的聚合酶(Pmut)设置成表达为融合蛋白。在其中免疫原表达盒编码HBV前核心的实施方式中,HBV前核心、HBV核心和修饰的聚合酶(Pmut)设置成表达为融合蛋白。
在一个实施方式中,该免疫原表达盒编码至少两种蛋白,其包含至少包含HBV核心和修饰的HBV聚合酶(Pmut)的第一融合蛋白,以及至少包含HBV表面抗原(HbsAg)的第二蛋白。在另一个实施方式中,该免疫原表达盒仅编码两种蛋白,其包含至少包含HBV核心和修饰的HBV聚合酶(Pmut)的第一融合蛋白,以及至少包含HBV表面抗原(HbsAg)的第二蛋白。
在一个实施方式中,该免疫原表达盒不编码HBV X蛋白。
在一个实施方式中,如本文所述,该免疫原表达盒可以包含编码以下中任一个的核酸序列:
SIi-HBV-CPmutS;
SIi-HBV-SCPmut;
HBV-CPmutS;
SIi-HBV-CPmutPreS-S(sh);
SIi-HBV-CPmutPreS-TPA-S(sh);
SIi-HBV-PreS-Pmut-C;
MVA-SIi-HBV-PreS-Pmut-C-S(sh);或
MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh)。
在一个实施方式中,该免疫原表达盒包含SEQ ID NO:46(SIi-HBV-CPmutS)或其变体。SEQ ID NO:46的变体可以包含与SEQ ID NO:46具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:46的变体可以编码基本上保留由SEQID NO:46编码的等效蛋白的免疫原性的蛋白。
在一个实施方式中,该免疫原表达盒包含SEQ ID NO:47(SIi-HBV-SCPmut)或其变体。SEQ ID NO:47的变体可以包含与SEQ ID NO:47具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:47的变体可以编码基本上保留由SEQID NO:47编码的等效蛋白的免疫原性的蛋白。
在另一个实施方式中,该免疫原表达盒包含SEQ ID NO:48(SIi-HBV-CPmutPreS-S(sh))或其变体。SEQ ID NO:48的变体可以包含与SEQ ID NO:48具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:48的变体可以编码基本上保留由SEQ ID NO:48编码的等效蛋白的免疫原性的蛋白。
在另一个实施方式中,该免疫原表达盒包含SEQ ID NO:49(SIi-HBV-CPmutPreS-TPA-S(sh))或其变体。SEQ ID NO:49的变体可以包含与SEQ ID NO:49具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:49的变体可以编码基本上保留由SEQ ID NO:49编码的等效蛋白的免疫原性的蛋白。
在一个实施方式中,该免疫原表达盒包含SEQ ID NO:59(SIi-HBV-PreS-Pmut-C)或其变体。SEQ ID NO:59的变体可以包含与SEQ ID NO:59具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:59的变体可以编码基本上保留由SEQ ID NO:59编码的等效蛋白的免疫原性的蛋白。
在一个实施方式中,该免疫原表达盒包含SEQ ID NO:24(MVA-SIi-HBV-PreS-Pmut-C-S(sh))或其变体。SEQ ID NO:24的变体可以包含与SEQ ID NO:24具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:24的变体可以编码基本上保留由SEQ ID NO:24编码的等效蛋白的免疫原性的蛋白。
在一个实施方式中,该免疫原表达盒包含SEQ ID NO:27(MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh))或其变体。SEQ ID NO:27的变体可以包含与SEQ ID NO:27具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:27的变体可以编码基本上保留由SEQ ID NO:27编码的等效蛋白的免疫原性的蛋白。在一个实施方式中,该免疫原表达盒包含SEQ ID NO:58(MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh))或其变体。SEQ ID NO:58的变体可以包含与SEQ ID NO:58具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:58的变体可以编码基本上保留由SEQID NO:58编码的等效蛋白的免疫原性的蛋白。
病毒载体
该病毒载体可以包含病毒。可将本发明的免疫原表达盒序列克隆到已知导致良好免疫应答的任何合适的病毒载体中。合适的病毒载体已经在Dicks等人(Vaccine.2015年2月25日;33(9):1121-8.doi:10.1016/j.vaccine.2015.01.042.Epub 2015年1月25日)、Antrobus等人(Mol Ther.2014Mar;22(3):668-74.doi:10.1038/mt.2013.284.Epub 2013年12月30日)和Warimwe等人(Virol J.2013年12月5日;10:349.doi:10.1186/1743-422X-10-349)中描述,其通过引用并入本文。
该病毒载体可以是减毒的病毒载体。该病毒载体可以包含腺病毒,例如人或猿猴腺病毒。在一个实施方式中,当用于初免加强方案的初免疫苗中时,该病毒载体包含腺病毒,例如E组猿猴腺病毒。该病毒载体可以包含E组猿猴腺病毒。该病毒载体可以包含ChAdOx1(E组猿猴腺病毒,如在疟疾试验中安全使用的AdCh63载体)或ChAdOx2。技术人员将熟悉例如来自专利公开号WO2012172277(其通过引用并入本文)的基于ChAdOx1的病毒载体。该病毒载体可以包含AdCh63。该病毒载体可以包含AdC3或AdH6。在一个实施方式中,该病毒载体是人血清型。在另一个实施方式中,该病毒载体包含修饰的安卡拉痘苗(MVA)。当在初免加强方案中用作疫苗加强剂时,该病毒载体可以包含MVA。在一个实施方式中,当用于初免加强方案的初免疫苗中时,该病毒载体包含腺病毒,例如E组猿猴腺病毒,当在初免加强方案中用作疫苗加强剂时,其可能包含MVA。技术人员将熟悉例如来自美国专利公开号US9273327(其通过引用并入本文)的基于MVA的病毒载体。
MVA有利地允许使用不同的痘病毒启动子表达一种以上蛋白。
在另一个实施方式中,该病毒载体可以包含腺相关病毒(AAV)或慢病毒。在另一个实施方式中,该病毒载体可以包含痘苗病毒、鸡痘病毒或金丝雀痘病毒(例如痘病毒科和禽痘病毒属的成员)或纽约减毒痘苗病毒(Tartaglia等人Virology.1992年5月;188(1):217-32,其通过引用并入本文)中的任一种。在另一个实施方式中,该病毒载体可以包含单纯疱疹病毒、人巨细胞病毒、麻疹病毒(MeV)、仙台病毒(SeV)、黄病毒(例如黄热病毒–17D)或甲病毒载体(例如辛德比斯病毒(SINV))、委内瑞拉马脑炎病毒或赛姆利基森林病毒中的任一种。
在一个实施方式中,该病毒载体可以包含具有SEQ ID NO:39和40(ChAdOx1)序列的核酸或其变体。SEQ ID NO:39和40的变体可以包含与SEQ ID NO:39和40具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:39和40的变体可以编码基本上保留SEQ ID NO:39和40(ChAdOx1)的病毒载体功能的病毒载体。
在一个实施方式中,该病毒载体可以包含具有SEQ ID NO:41和42(ChAdOx2)序列的核酸或其变体。SEQ ID NO:41和42的变体可以包含与SEQ ID NO:41和42具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:41和42的变体可以编码基本上保留SEQ ID NO:41和42(ChAdOx2)的病毒载体功能的病毒载体。
在一个实施方式中,该病毒载体可以包含具有SEQ ID NO:44和45(MVA)序列的核酸或其变体。SEQ ID NO:44和45的变体可以包含与SEQ ID NO:44和45具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:44和45的变体可以编码基本上保留SEQ ID NO:44和45(MVA)的病毒载体功能的病毒载体。
在一个实施方式中,该病毒载体编码以下中的任一个:
SIi-HBV-CPmutS;
SIi-HBV-SCPmut;
SIi-HBV-CPmutPreS-S(sh);
SIi-HBV-CPmutPreS-TPA-S(sh);
MVA-SIi-HBV-PreS-Pmut-C-S(sh);或
MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh)。
在一个实施方式中,该病毒载体编码SEQ ID NO:3(SIi-HBV-CPmutS)或其变体。SEQ ID NO:3的变体可以包含与SEQ ID NO:3具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:3的变体可以基本上保留SEQ ID NO:3的免疫原性。
在一个实施方式中,该病毒载体编码SEQ ID NO:11(SIi-HBV-SCPmut)或其变体。SEQ ID NO:11的变体可以包含与SEQ ID NO:11具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:11的变体可以基本上保留SEQ ID NO:11的免疫原性。
在一个实施方式中,该病毒载体编码SEQ ID NO:13(SIi-HBV-CPmutPreS-S(sh))或其变体。SEQ ID NO:13的变体可以包含与SEQ ID NO:13具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:13的变体可以基本上保留SEQID NO:13的免疫原性。
在一个实施方式中,该病毒载体编码SEQ ID NO:25(SIi-HBV-CPmutPreS-TPA-S(sh))或其变体。SEQ ID NO:25的变体可以包含与SEQ ID NO:25具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:25的变体可以基本上保留SEQ ID NO:25的免疫原性。
在一个实施方式中,该病毒载体编码SEQ ID NO:23(MVA-SIi-HBV-PreS-Pmut-C-S(sh))或其变体。SEQ ID NO:23的变体可以包含与SEQ ID NO:23具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:23的变体可以基本上保留SEQ ID NO:23的免疫原性。
在一个实施方式中,该病毒载体编码SEQ ID NO:26(MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh))或其变体。SEQ ID NO:26的变体可以包含与SEQ ID NO:26具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:26的变体可以基本上保留SEQ ID NO:26的免疫原性。
在一个实施方式中,该病毒载体包含核酸序列SEQ ID NO:46(SIi-HBV-CPmutS)或其变体。SEQ ID NO:46的变体可以包含与SEQ ID NO:46具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。
在一个实施方式中,该病毒载体包含核酸序列SEQ ID NO:47(SIi-HBV-SCPmut)或其变体。SEQ ID NO:47的变体可以包含与SEQ ID NO:47具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。
在一个实施方式中,该病毒载体包含核酸序列SEQ ID NO:48(SIi-HBV-CPmutPreS-S(sh))或其变体。SEQ ID NO:48的变体可以包含与SEQ ID NO:48具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。
在一个实施方式中,该病毒载体包含核酸序列SEQ ID NO:49(SIi-HBV-CPmutPreS-TPA-S(sh))或其变体。SEQ ID NO:49的变体可以包含与SEQ ID NO:49具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。
在一个实施方式中,该病毒载体包含核酸序列SEQ ID NO:24(MVA-SIi-HBV-PreS-Pmut-C-S(sh))或其变体。SEQ ID NO:24的变体可以包含与SEQ ID NO:24具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。
在一个实施方式中,该病毒载体包含核酸序列SEQ ID NO:27(MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh))或其变体。SEQ ID NO:27的变体可以包含与SEQ ID NO:27具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。在一个实施方式中,该病毒载体包含核酸序列SEQ ID NO:58(MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh))或其变体。SEQ ID NO:58的变体可以包含与SEQ ID NO:58具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。
启动子
在一个实施方式中,启动子编码在免疫原表达盒中,例如,该启动子可以编码在免疫原表达盒的5'端或与5'端相邻。可替代地,可以将该启动子编码为免疫原表达盒外部的病毒载体核酸的一部分。例如,该启动子可以编码在免疫原表达盒的上游(5’)。
该启动子可以促进免疫原表达盒的所有编码蛋白的表达。在其中免疫原表达盒包含次级启动子的替代实施方式中,该启动子可以是初级启动子,其设置为至少可以促进HBV核心和修饰的聚合酶(Pmut)的表达,并且任选地不促进设置为由次级启动子单独促进的HBV表面抗原(HbsAg)的表达。
技术人员将认识到任何合适的启动子都可以用作适合于表达宿主的初级和/或次级启动子。在一个实施方式中,该启动子包含CMV启动子。该CMV启动子可以包含长或短CMV启动子。在其中病毒载体包括腺病毒载体(例如ChAdOx1或2)的实施方式中,该启动子可以包含CMV启动子、SV40启动子或EF1a启动子。在其中病毒载体包括腺病毒载体(例如ChAdOx1或2)的实施方式中,该启动子可以包含CMV启动子。
用于载体(例如腺病毒载体(例如ChAdOx1或2))的启动子元件可以包含四环素操纵子(tetO)序列。四环素操纵子(tetO)序列有助于产生病毒载体,该四环素操纵基因(tetO)序列有助于产生病毒载体,该病毒载体可以表达对产生它们的细胞有毒的外源蛋白。
在另一个实施方式中,该启动子包括痘病毒启动子。在病毒载体包含MVA的实施方式中,该启动子可以包含痘病毒启动子,例如F11。在一个实施方式中,该启动子包含早期F11启动子。可替代地,该痘病毒启动子可以包含早期启动子(例如选自B8R、K6L、A44L、C11R和B2R中的任一种),具有早期和晚期活性的启动子(例如选自mH5、p7.5和SSP中的任一种)或晚期启动子(例如FP4b)。
基于早期启动子的转基因表达可用于旨在主要用于T细胞应答的免疫原(使用这些早期启动子时,T细胞的诱导程度更高)。然而,具有早期和晚期活性的启动子可以旨在用于诱导抗体应答的免疫原。然而,这些早期和晚期活性的启动子也可以旨在用于T细胞诱导的免疫原。
在一个实施方式中,该启动子包含核酸序列SEQ ID NO:50或52(CMV长或短启动子)或其变体、或由其组成。SEQ ID NO:50或52的变体可以包含分别与SEQ ID NO:50或52具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。该变体可以基本上保留SEQ ID NO:50或52的启动子功能。
在一个实施方式,该启动子包含位于F11左翼序列中的序列(SEQ ID NO:35)或其变体、或由其组成。该变体可以包含与位于F11左翼序列中的启动子序列具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。该变体可以基本上保留位于F11左翼序列中的启动子(SEQ ID NO:35)的启动子功能。
次级启动子
在一个实施方式中,该免疫原表达盒编码次级启动子。在其中除了第一/初级启动子外还提供次级启动子的实施方式中,该次级启动子可以由免疫原表达盒/在免疫原表达盒中编码。可以将该次级启动子编码为第一/初级启动子的3’端。可以将次级启动子编码为待表达的第一个蛋白/抗原的3'端,例如在HBV核心和HBV修饰的聚合酶的下游以及HBV表面抗原的上游。该次级启动子可以促进至少HBV表面抗原的表达。
该次级启动子可以包含痘病毒启动子。该次级启动子可以包含痘病毒早期启动子(例如B8R、K6L、A44L、C11R和B2R中的任一个),或具有早期和晚期活性的痘病毒启动子(例如mH5、p7.5或SSP)或晚期启动子(例如FP4b)。
在一个实施方式中,该次级启动子包含早期/晚期启动子mH5。在一个实施方式中,该次级启动子包含核酸序列SEQ ID NO:28(mH5启动子)或其变体、或由其组成。SEQ ID NO:28的变体可以包含与SEQ ID NO:28具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。该变体可以基本上保留SEQ ID NO:28的次级启动子功能。
在另一个实施方式中,该次级启动子可以包含SV40启动子或EF1a启动子。
切割结构域
在一个实施方式中,该免疫原表达盒编码切割结构域。在一个实施方式中,该切割结构域是翻译后蛋白水解切割结构域,其允许例如通过蛋白水解切割酶切割翻译的蛋白。该切割酶可以由宿主提供,例如被接种疫苗的宿主(例如人)。在另一个实施方式中,可以在免疫原表达盒或病毒载体中编码该切割酶。在一个实施方式中,该切割结构域包含非HBV序列,例如哺乳动物序列。在一个实施方式中,该切割结构域包含人衍生序列。
在一个实施方式中,该切割结构域包含核糖体跳跃切割结构域。在一个实施方式中,该切割结构域包含弗林蛋白酶(Furin)识别位点,该识别位点包含序列RXRR、或由其组成,其中X可以是任何氨基酸。在一个实施方式中,该切割结构域包含弗林蛋白酶识别位点和2A肽序列。该2A肽序列可能包含FMDV(口蹄疫病毒)2A肽序列(APVKQTLNFDLLKLAGDVESNPGP-SEQ ID NO:43)。可替代地,该2A肽可以选自P2A(猪破伤风病毒-1 2A)、T2A(明脉扁刺蛾β四体病毒2A(Thoseaasigna virus 2A))和E2A(马鼻炎A病毒[ERAV]2A)。可以提供任何小核糖核酸病毒2A肽序列,并用作肽切割位点。因此,该切割结构域可以包含编码小核糖核酸2A肽序列的序列。
在一个实施方式中,该切割结构域包含弗林蛋白酶-2A(F2A)肽序列或其功能变体、或由其组成。该切割结构域可以包含序列SEQ ID NO:9或其变体、或由其组成。SEQ IDNO:9的变体可以包含与SEQ ID NO:9具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:9的变体可以基本上保留SEQ ID NO:9的切割功能。
F2A有利地是短的(仅28个氨基酸),这有助于提供合适的插入片段并由可能具有大小限制的载体(例如基于腺病毒的载体,包括ChAdOx1/2)表达一种以上的蛋白。
在其中病毒载体是MVA或者在初次接种疫苗后以其它方式将病毒载体用作加强接种疫苗的实施方式中,可以提供不同的切割结构域以避免T细胞对初免接种疫苗的切割结构域的任何潜在加强。可替代地,可以使用次级启动子代替切割结构域以便避免T细胞对初免接种疫苗的切割结构域的任何潜在加强。
IRES(内部核糖体进入位点)
在一个实施方式中,该免疫原表达盒编码内部核糖体进入位点(IRES)。技术人员将认识到IRES是RNA结构,其允许帽独立地启动翻译,并且能够在信使RNA的中间启动翻译。
剪接信号
在一个实施方式中,该免疫原表达盒编码mRNA剪接信号。技术人员将熟悉适合于此用途的常用剪接信号。可以使用的mRNA剪接信号的这种示例是由人β-珠蛋白基因和分支的第一个内含子的5’供体位点和表达载体pCI-neo哺乳动物表达载体(Promega)中的免疫球蛋白基因重链可变区的内含子的3’受体位点组成的嵌合内含子。
HBV前核心(PreC)
HBV PreC可以包含全长野生型HBV PreC序列或其变体、或由其组成。HBV PreC变体可以包含截短的HBV PreC序列、或由其组成。
HBV PreC可以包含序列SEQ ID NO:16或其变体、或由其组成。SEQ ID NO:16的变体可以包含与SEQ ID NO:16具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:16的变体可以基本上保留SEQ ID NO:16的免疫原性。SEQID NO:16的变体可以基本上保留SEQ ID NO:16的三级结构。
HBV核心
HBV核心可以包含全长野生型HBV核心序列或其变体、或由其组成。HBV核心变体可以包含截短的HBV核心序列、或由其组成。HBV核心可以不包含HBV前核心。
HBV核心可以包含序列SEQ ID NO:6或其变体、或由其组成。SEQ ID NO:6的变体可以包含与SEQ ID NO:6具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:6的变体可以基本上保留SEQ ID NO:6的免疫原性。SEQ ID NO:6的变体可以基本上保留SEQ ID NO:6的三级结构。
HBV e-抗原(HBeAg)
HBV e-抗原(HBeAg)可以包含全长野生型HBV e-抗原序列或其变体、或由其组成。HBV e-抗原变体可以包含截短的HBV e-抗原序列、或由其组成。
HBV e-抗原(HBeAg)可以包含以下序列、或由其组成:
SKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVV(SEQ ID NO:17)。
HBV e-抗原(HBeAg)包含序列SEQ ID NO:17或其变体、或由其组成。SEQ ID NO:17的变体可以包含与SEQ ID NO:17具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:17的变体可以基本上保留SEQ ID NO:17的免疫原性。SEQID NO:17的变体可以基本上保留SEQ ID NO:17的三级结构。
修饰的HBV聚合酶
修饰的HBV聚合酶(Pmut)可以包含截短的HBV聚合酶、或由其组成。特别地,野生型HBV聚合酶的突变以基本上除去聚合酶功能可以包含编码截短的HBV聚合酶的序列。可替代地或另外地,该突变包含编码的HBV聚合酶序列的一个或多个点突变。该修饰可以包含在编码的HBV聚合酶序列中的一个或多个氨基酸取代、缺失或添加。在一个实施方式中,修饰的HBV聚合酶(Pmut)不是HBV聚合酶的截短形式(即其相对于野生型HBV聚合酶是全长的)。
修饰的HBV聚合酶(Pmut)可以包含SEQ ID NO:8或其变体、或由其组成。SEQ ID NO:8的变体可以包含与SEQ ID NO:8具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:8的变体可以基本上保留SEQ ID NO:8的免疫原性。SEQID NO:8的变体可以基本上保留SEQ ID NO:8的三级结构。
该修饰可以是阻止蛋白初免的突变。另外地或可替代地,可以在逆转录酶和/或RNA酶结构域中提供突变以阻止其功能。进一步,另外地或可替代地,该突变可以是结构性的,使得破坏聚合酶的正确蛋白折叠。通过参考本文的野生型HBV聚合酶共有序列(即SEQID NO:19),该修饰可以包含Y63、C323、C334、C338、C352、R714、D788、R792或其等同残基中的一个或多个或全部。在一个实施方式中,通过参考本文的野生型HBV聚合酶共有序列(即SEQ ID NO:19),该修饰可以包含Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A或其等同残基中的一个或多个或全部。在另一个实施方式中,通过参考本文的野生型HBV聚合酶共有序列(即SEQ ID NO:19),该修饰可以包含R714、D788和R792或其等同残基中的一个或多个或全部。在一个实施方式中,通过参考本文的野生型HBV聚合酶共有序列(即SEQ IDNO:19),该修饰可以包含R714A、D788A和R792A或其等同残基中的一个或多个或全部。参考等同残基应理解为是指HBV聚合酶可以基于本文所提供的HBV聚合酶序列外的可替换序列,并且氨基酸残基的编号或同一性在序列之间可以不同。通过将HBV聚合酶序列与本文的野生型HBV聚合酶共有序列(即SEQ ID NO:19)进行比对,可以容易地确定这种差异和等同性。
突变R714A、D788A、R792A有利地停止了聚合酶功能。然而,如果在这些功能性突变内发生逆转,则可以添加Y63的额外突变和其它半胱氨酸突变(C323、C334、C338和C352)中的一个或多个或全部作为额外措施。额外突变可以包含Y63A、C323A、C334A、C338A和/或C352A。
所述突变有利地提供了HBV聚合酶功能被(a)RNA酶H功能性突变破坏以停止其酶活性,和/或(b)Y63A突变破坏以停止复制的第一步(DNA合成的初免),和/或(c)半胱氨酸突变破坏以破坏其天然构象并阻止HBV聚合酶参与病毒复制的初始步骤(蛋白初免、RNA结合和RNA包装)。
技术人员将熟悉可以提供的各种HBV聚合酶修饰,其显著降低或消除功能,并且可以在根据本发明的修饰的聚合酶中提供。例如在WO2016020538、WO2013007772和WO2011015656中描述了这种修饰,其通过引用并入本文。
在一个实施方式中,将经修饰的聚合酶修饰以便相对于野生型HBV聚合酶表现出降低的逆转录酶(RTase)酶活性。可以通过负责RTase酶活性的结构域中的一个或多个突变来提供RTase活性的降低。
已经发现四个残基参与RTase活性,在野生型HBV聚合酶的约位置538至约位置541处形成基序“YMDD”(用于Tyr、Met、Asp和Asp残基)。本发明涵盖该基序或RTase结构域中其它地方的任何突变,该突变提供RTase活性的显著降低(例如至少降低10倍)或消除。合适的RTase-缺陷型聚合酶突变体的代表性示例描述于Radziwill等人(1990,J.Virol.64:613)、Bartenschlager等人(1990,J.Virol.64:5324)和Jeong等人(1996,Biochem Bioph ResCommun.223(2):264)中,其通过引用并入本文。在一个实施方式中,经修饰的聚合酶可以包含将YMDD基序的第一个Asp残基或位于天然HBV聚合酶中等同位置的氨基酸残基取代为除Asp外的任何氨基酸残基,任选地取代为His残基(D540H突变)。
在一个实施方式中,将经修饰的聚合酶修饰以相对于野生型HBV聚合酶提供降低的RNase H酶活性。可以通过负责RNase H酶活性的结构域中的一个或多个突变来提供RNase H活性的降低。涉及RNase H活性的功能性结构域在HBV聚合酶的C末端部分内,约从野生型聚合酶的位置680到C端位置832,并且本发明的经修饰的聚合酶可以涵盖提供RNaseH活性显著降低(例如至少降低10倍)或消除的该结构域中的任何突变。合适的RNase H-缺陷型聚合酶突变体的代表性示例描述于Radziwill等人(1990,J.Virol.64:613)、Bartenschlager等人(1990,J.Virol.64:5324)中。
HBV表面抗原(HbsAg)
技术人员将理解PreS1和PreS2是HBV表面蛋白的大(L)形式的组分(例如L形式=PreS1+PreS2+S)。HBV表面蛋白的中等(M)形式具有PreS2+S。将这些序列放在一起意味着以这些顺序包括T细胞表位。
HbsAg可以包含全长野生型HbsAg序列或其变体、或由其组成。HbsAg变体可以包含截短的HbsAg序列、或由其组成。
包括PreS1和PreS2序列的HbsAg可以包含序列SEQ ID NO:10或其变体、或由其组成。SEQ ID NO:10的变体可以包含与SEQ ID NO:10具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:10的变体可以基本上保留SEQ ID NO:10的免疫原性。SEQ ID NO:10的变体可以基本上保留SEQ ID NO:10的三级结构。
在另一个实施方式中,HbsAg可以包含没有PreS1和/或PreS2的表面抗原。HbsAg可以包含序列SEQ ID NO:18或其变体、或由其组成。SEQ ID NO:18的变体可以包含与SEQ IDNO:18具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQID NO:18的变体可以基本上保留SEQ ID NO:18的免疫原性。SEQ ID NO:18的变体可以基本上保留SEQ ID NO:18的三级结构。
在一个实施方式中,HbsAg可以包含HbsAg(氨基酸1-226)中四个已知的跨膜区中的任一个或全部、或由其组成,这些跨膜区为氨基酸(8-32)FLGPLLVLQAGFFLLTRILTIPQSL(SEQ ID NO:54)、氨基酸(80-98)FIIFLFILLLCLIFLLVLL(SEQ ID NO:55)、氨基酸(160-184)RFLWEWASVRFSWLSLLVPFPFVQWFV(SEQ ID NO:56)和氨基酸(189-210)TVWLSVIWMMWYWGPSLYNILS(SEQ ID NO:57)。在一个实施方式中,HbsAg可以至少包含氨基酸(8-32)FLGPLLVLQAGFFLLTRILTIPQSL(SEQ ID NO:54)的HbsAg跨膜区、或由其组成。
HBV PreS1
HBV PreS1可以包含全长野生型HBV PreS1序列或其变体、或由其组成。HBV PreS1可以包含序列SEQ ID NO:52或其变体、或由其组成。SEQ ID NO:52的变体可以包含与SEQID NO:52具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:52的变体可以基本上保留SEQ ID NO:52的免疫原性。SEQ ID NO:52的变体可以基本上保留SEQ ID NO:52的三级结构。
HBV PreS1变体可以包含截短的HBV PreS1序列、或由其组成,例如本文所述的CΔPreS1或NΔPreS1(CΔPreS1是指C末端截短的PreS1,而NΔPreS1是指N末端截短的PreS1)。在一个实施方式中,免疫原表达盒可以编码NΔPreS1和CΔPreS1两者。在其中免疫原表达盒编码NΔPreS1和CΔPreS1两者的实施方式中,NΔPreS1编码可以在基因间序列的上游(5’),并且CΔPreS1可以编码在基因间序列的下游(3’)。在免疫原表达盒在基因间序列上游(5’)编码NΔPreS1的实施方式中,它可以与PreS2和/或经修饰的聚合酶(Pmut)融合。在其中免疫原表达盒在基因间序列的上游(5')编码NΔPreS1的实施方式中,它可以与PreS2和/或经修饰的聚合酶(Pmut)融合,并且在基因间序列的下游(3’)编码的CΔPreS1可以与表面抗原(HbsAg)融合。
CΔPreS1
在一个实施方式中,该免疫原表达盒编码截短形式的HBV PreS1。该截短可以包含C末端截短。在一个实施方式中,截短的HBV PreS1包含本文所述的CΔPreS1(SEQ ID NO:21)。在一个实施方式中,截短的PreS1(例如本文所述的CΔPreS1)设置为表达与HBV表面抗原的融合蛋白(S/HbsAg)。可以在截短的PreS1和表面抗原(S/HbsAg)之间提供接头序列,例如本文所述的接头。例如,CΔPreS1+接头+S(本文所述为S(sh))。编码S(sh)的核苷酸序列可以包含SEQ ID NO:61或SEQ ID NO:38、或由其组成。
CΔPreS1可以包含序列SEQ ID NO:21或其变体、或由其组成。SEQ ID NO:21的变体可以包含与SEQ ID NO:21具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:21的变体可以基本上保留SEQ ID NO:21的免疫原性。SEQID NO:21的变体可以基本上保留SEQ ID NO:21的三级结构。
在一个实施方式中,截短的PreS1(例如本文所述的CΔPreS1)任选地具有融合的表面抗原,其编码在基因间序列的下游(3’)。
PreS1截短有利于促进T细胞的抗体产生以及免疫原表达盒中所提供的HBV抗原的抗体应答。不受理论的束缚,抗体的产生可能是由于PreS1和表面抗原的适当折叠。
NΔPreS1
在一个实施方式中,截短的PreS1包含如本文所述的NΔPreS1。NΔPreS1和PreS2融合体可以包含SEQ ID NO:15或其变体、或由其组成。SEQ ID NO:15的变体可以包含与SEQID NO:15具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:15的变体可以基本上保留SEQ ID NO:15的免疫原性。
在一个实施方式中,截短的PreS1包含如本文所述的NΔPreS1。NΔPreS1和PreS2融合体可以由包含SEQ ID NO:38或61或其变体、或由其组成的核酸编码。SEQ ID NO:38和61的变体可以包含与SEQ ID NO:38和61具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:38或61的编码变体可以基本上保留由SEQ ID NO:38或61编码的肽的免疫原性。
NΔPreS1和PreS2融合序列有利地提供了良好的T细胞应答。NΔPreS1有利地包括在仍将保留T细胞表位的序列中的氨基酸(对于CD8 T细胞表位为8-11个氨基酸,而对于CD4T细胞表位则稍长(12-16个))。
在其中免疫原表达盒编码与基因间序列上游(5’)的PreS2融合的NΔPreS1的实施方式中,它可以进一步与经修饰的聚合酶(Pmut)融合。可以在PreS2和经修饰的聚合酶(Pmut)之间提供接头序列,例如本文所述的接头。例如,NΔPreS1+PreS2+接头+Pmut。
HBV PreS2
HBV PreS2可以包含全长野生型HBV PreS2序列或其变体、或由其组成。HBV PreS2变体可以包含截短的HBV PreS2序列、或由其组成。
HBV PreS2可以包含序列SEQ ID NO:53或其变体、或由其组成。SEQ ID NO:53的变体可以包含与SEQ ID NO:53具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:53的变体可以基本上保留SEQ ID NO:53的免疫原性。SEQID NO:53的变体可以基本上保留SEQ ID NO:53的三级结构。
肽佐剂
该免疫原表达盒可以进一步编码肽佐剂。该肽佐剂可以包含TPA(组织纤溶酶原活化剂)。在一个实施方式中,该肽佐剂可以包含人或非人不变链(Ii)或其片段。人CD74分子的长异构体(异构体(b))的片段也称为不变链(Nucleic Acids Res.1985December 20;13(24):8827-8841)。已知的是,在表达为与目的抗原的融合蛋白时,至少包含其跨膜结构域的不变链(li)的N末端片段提供了令人惊讶的有效佐剂功能。涵盖跨膜结构域和胞质结构域(优选地包括蛋白的长异构体的N末端16个氨基酸)的片段是特别有效的。
该不变链可以包含鲨鱼不变链(SIi)或其片段或功能性变体、或由其组成。变体鲨鱼不变链(SIi)可以包含截短的恒定的鲨鱼不变链。不变链或其片段的其它非人动物来源包括鸡、鹌鹑、鳟鱼、斑马鱼、鲤鱼、青蛙、石斑鱼、鲨鱼、桂鱼或野鸭。技术人员将熟悉用作在表达盒/载体中编码的肽佐剂(例如不变链)的合适的不变链或其片段可以是如WO2015082922中所提供的任何不变链,其通过引用并入本文。
该肽佐剂可以包含序列SEQ ID NO:4(S1i)或其变体、或由其组成。SEQ ID NO:4的变体可以包含与SEQ ID NO:4具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:4的变体可以基本上保留SEQ ID NO:4的佐剂功能。
该肽佐剂可以由包含序列SEQ ID NO:29(TPA核酸序列)或其变体、或由其组成的序列编码。SEQ ID NO:29的变体可以包含与SEQ ID NO:29具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:29的变体可以编码基本上保留由SEQ ID NO:29编码的TPA的佐剂功能的肽佐剂。该肽佐剂可以由包含序列SEQ ID NO:60(TPA核酸序列)或其变体、或由其组成的序列编码。SEQ ID NO:60的变体可以包含与SEQ IDNO:60具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQID NO:60的变体可以编码基本上保留由SEQ ID NO:60编码的TPA的佐剂功能的肽佐剂。
该肽佐剂可以包含序列SEQ ID NO:30(TPA)或其变体、或由其组成。SEQ ID NO:30的变体可以包含与SEQ ID NO:30具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:30的变体可以基本上保留SEQ ID NO:30的佐剂功能。
该肽佐剂可以在待由免疫原表达盒表达的蛋白/抗原的N末端位置编码。第一肽佐剂可以在待由免疫原表达盒表达的第一蛋白/抗原(例如核心和聚合酶融合体)的N末端位置编码,且第二肽佐剂可以在待由免疫原表达盒表达的第二蛋白/抗原(例如表面抗原)的N末端位置编码。
HBV基因型
HBV可以是HBV基因型C。在另一个实施方式中,HBV可以是10种基因型(A-J)中的任何一种。所有编码的HBV蛋白/抗原都可以源自一种基因型,例如HBV基因型C。
接头
在一个实施方式中,可以在融合蛋白中提供的一种或多种或全部蛋白/抗原序列之间(例如在蛋白中的序列之间提供连接)编码接头残基。在包含肽佐剂的实施方式中,可以在肽佐剂和下游编码的蛋白/抗原之间编码接头。在一个实施方式中,在HBV核心和经修饰的HBV聚合酶的序列之间编码接头。
接头残基可以包含随机氨基酸序列,或已基于表位预测计算机程序或动物模型中的实验选择为非免疫原性的氨基酸。例如,如果预测或已知其为表位(即为了避免对HBV中未发现的表位(例如人工表位)产生免疫应答),则可以不考虑该接头。该接头可以是柔性的。该接头可以包含K、G、P或S个氨基酸残基或其组合、或由其组成。在一个实施方式中,该接头可以包含G和/或P个氨基酸残基、或由其组成。该接头残基的长度可以在1至10个氨基酸之间。在另一个实施方式中,该接头残基的长度可以在2至8个残基之间。在另一个实施方式中,该接头残基的长度可以在1至6个残基之间。
该接头可以包含序列KGGGPGGG(SEQ ID NO:5)、GGGSGGG(SEQ ID NO:7)、KGGS(SEQID NO:14)、KSP、GSKGK(SEQ ID NO:20)、LEGGSGG(SEQ ID NO:22)、SKSGPPSGKS(SEQ ID NO:31)、GSKSGSK(SEQ ID NO:32)、SKSPGSGPP(SEQ ID NO:33)或ASKGGKSG(SEQ ID NO:34)中的任一种、或由其组成。
在一个实施方式中,该接头可以包含序列KGGGPGGG(SEQ ID NO:5)。在另一个实施方式中,该接头可以包含序列GGGSGGG(SEQ ID NO:7)。在另一个实施方式中,该接头可以包含序列KGGS(SEQ ID NO:14)。在另一个实施方式中,该接头可以包含序列KSP。在另一个实施方式中,该接头可以包含序列GSKGK(SEQ ID NO:20)。在另一个实施方式中,该接头可以包含序列LEGGSGG(SEQ ID NO:22)。在另一个实施方式中,该接头可以包含序列SKSGPPSGKS(SEQ ID NO:31)。在另一个实施方式中,该接头可以包含序列GSSKSGK(SEQ ID NO:32)。在另一个实施方式中,该接头可以包含序列SKSPGSGPP(SEQ ID NO:33)。在另一个实施方式中,该接头可以包含序列ASKGGKSG(SEQ ID NO:34)。
有利地,使用接头可以避免产生与人蛋白质组同源的肽(其可能产生对自身抗原的免疫应答),并且它们避免了以免疫为主的人工表位。另外,接头可以在蛋白片段之间提供柔性铰链,使得它们可以折叠成其天然构象。例如,CΔPreS1和S之间的接头允许CΔPreS1和S独立地折叠,使得它们可以产生相应蛋白构象表位的抗体。
接头可以在不同的免疫原表达盒之间变化。使用不同的接头避免了对任何潜在的人工表位产生的任何T细胞应答的增强(即通过改变接头或改变连接)。例如,当疫苗用于初免加强接种疫苗策略时,改变免疫原布局内的接头或蛋白顺序有助于克服人工表位应答的加强。
免疫原表达盒的其它元件
在其中免疫原表达盒用于MVA载体的实施方式中,该免疫原表达盒可以进一步包含F11左右侧翼序列以允许通过同源重组插入到MVA F11基因座中。
F11左侧翼序列可以包含SEQ ID NO:35或其变体、或由其组成。F11右侧翼序列可以包含SEQ ID NO:36或其变体、或由其组成。SEQ ID NO:35或36的变体可以包含分别与SEQID NO:35或36具有至少70%、75%、80%、85%、90%、95%、98%、99%或99.5%同一性的序列。SEQ ID NO:35或36的变体可以分别基本上保留SEQ ID NO:35或36的同源重组功能。技术人员将理解,可以在不影响功能的情况下取代、添加或除去1、2、3、4、5或更多个氨基酸残基。例如,可以考虑保守取代。
该免疫原表达盒可以进一步包含转录终止子序列。可以在包含次级启动子的免疫原表达盒的实施方式中提供转录终止子序列。例如,该转录终止子序列可以提供在初级启动子表达的蛋白的下游,但是在次级启动子之前(上游)。该转录终止子序列可以包含序列TTTTTGT或其变体、或由其组成。
在一个实施方式中,可以在非病毒载体中分离或提供本文所述的免疫原表达盒。
因此,根据本发明的另一方面,提供了一种核酸,其包含本文所述的免疫原表达盒,任选地其中,所述核酸是经分离的核酸。
根据本发明的另一方面,提供了一种组合物,其包含根据本发明的病毒载体,任选地其中,所述组合物是药学上可接受的组合物。
该组合物可以是免疫原性的,例如在哺乳动物(例如人)中。该组合物可以包含药学上可接受的载体。该组合物可以是包含药学上可接受的载体的药物组合物。该组合物可以用于预防或治疗HBV感染。
根据本发明的另一方面,提供了一种治疗或预防HBV感染的方法,其包括施用根据本发明的病毒载体、核酸或组合物。
治疗或预防HBV感染的方法可以是接种疫苗的方法。
根据本发明的另一方面,提供了一种根据本发明的病毒载体、核酸或组合物在治疗或预防HBV感染中的用途,任选地其中,该用途是在疫苗中。
根据本发明的另一方面,提供了一种疫苗,其包含根据本发明的病毒载体、核酸或组合物。
该疫苗可以是初免疫苗。该疫苗可以是加强疫苗。在初免疫苗之后提供加强疫苗的情况下,该病毒载体可以是根据本发明的不同的病毒载体。
有利地,在初免和加强疫苗之间提供不同的病毒载体可以避免提供跨一种蛋白/抗原序列与另一种蛋白/抗原序列的连接形成的“假”表位,即在重新排序的蛋白中可能不会出现相同的连接。
根据本发明的另一方面,提供了一种初免加强接种疫苗试剂盒,其包含:
-根据本发明的初免接种疫苗;
-根据本发明的加强接种疫苗。
初免和加强接种疫苗可以包含不同的病毒载体。
该病毒载体可以与另一种治疗或预防活性成分组合用于疫苗。该病毒载体可以与佐剂组合用于疫苗。
可以在药学上可接受的载体中提供病毒载体、编码病毒载体的核酸。
根据本发明的病毒载体或组合物可以不包含野生型HBV,或者根据本发明的核酸可以不编码野生型HBV。
本文所用的对序列“同一性”的参考可以指使用标准NCBI BLASTp参数(http://blast.ncbi.nlm.nih.gov)的两个比对序列之间的同一性百分比。
当将术语“免疫原性的”应用于本发明的病毒载体、核酸或组合物时,是指能够在人或动物体内引发免疫应答。该免疫应答可以对HBV是保护性的。术语“保护性的”是指预防乙型肝炎疾病,降低乙型肝炎疾病的风险,降低乙型肝炎病毒感染、传播和/或进展的风险,降低乙型肝炎疾病的严重程度,治愈乙型肝炎,减轻乙型肝炎的症状或降低乙型肝炎疾病症状的严重程度。
术语“预防”是指对乙型肝炎的预防或保护性治疗。预防可以包括降低HBV感染、传播和/或乙型肝炎疾病进展的风险或降低乙型肝炎疾病的严重程度。
术语“治疗”是指治愈乙型肝炎、减轻症状或降低乙型肝炎疾病或乙型肝炎疾病症状的严重程度。
关于“变体”核酸序列,技术人员将理解,可以在不影响功能的情况下取代、添加或除去1、2、3、4、5或更多个密码子。例如,可以考虑保守取代。
关于“变体”氨基酸序列,技术人员将理解,可以在不影响功能的情况下取代、添加或除去1、2、3、4、5或更多个氨基酸。例如,可以考虑保守取代。
技术人员将理解,在适当的情况下,本发明的一个实施方式或方面的任选特征可以适用于本发明的其它实施方式或方面。
附图说明
现在将仅通过举例的方式,参考附图更详细地描述本发明的实施方式。
图1:(A)用于产生共有序列的1447个HBV基因型C序列的亲缘关系(B)HBV基因型C共有序列(SEQ ID NO:1)和KP017269.1HBV分离株JP-02(SEQ ID NO:2)的比较。使用MAFFT(多序列比对程序)将从HBV数据库(HBVdb:https://hbvdb.ibcp.fr/HBVdb/HBVdbIndex)下载的1447个HBV基因型C核苷酸序列进行比对以产生HBV基因型C共有序列和系统发育树和。共有序列的3215个核苷酸序列与所选患者的序列(KP017269.1HBV分离株JP-02)的比对显示出三个核苷酸差异(在52、1053和2699位置),其被突出显示为灰色。下面提供了从1447个基因型c分离株jp-02产生的HBV基因型C共有序列的序列。
图2:(A)HBV病毒基因组和密码子布局。HBV病毒粒子具有部分双链DNA(具有全长负链DNA和与聚合酶蛋白连接的部分合成的正链DNA)。基因组的长度约为3.2Kb且具有四个主要密码子:核心(包括前核心区)、聚合酶、表面(包括preS1和preS2区)和X。(B)HBV免疫原布局。设计了两种免疫原SIi-HBV-CPmutS和SIi-HBV-SCPmut。两种免疫原均编码HBV密码子(涵盖前核心、核心、聚合酶[Pmut]、preS1、preS2和表面蛋白)和非HBV密码子(包含截短的鲨鱼不变链[SIi]、两个接头[以翠蓝色表示]和一个弗林蛋白酶2A[F2A]肽序列)。在哺乳动物表达盒内,将该免疫原密码子序列置于CMV启动子附近。(C)体外表达分析。将编码SIi-HBV-CPmutS和SIi-HBV-SCPmut的质粒转染到HEK293A细胞中。转染后24小时,将细胞裂解,并使用小鼠抗HBV-PreS1和小鼠抗HBV聚合酶抗体在蛋白印迹实验中分析裂解物。将用小鼠抗GAPDH探测的印迹用作上样对照。(D)ChAdOX2-SIi-HBV-CPmutS。将具有SIi-HBV-CPmutS免疫原密码子的哺乳动物表达盒插入到复制缺陷型ChAdOx2载体中。通过使用前述标准方法将ChAdOX2-SIi-HBV-CPmutS载体转染到T-RExTM-293细胞(Thermo Fisher Scientific)中产生了重组ChAdOX2-SIi-HBV-CPmutS病毒。
图3:在幼稚小鼠模型中测试ChAdOx2-SIi-HBV-CPmutS疫苗。(A)BALB/c小鼠的脾细胞应答(B)BALB/c小鼠的肝内淋巴细胞应答(C)CD1小鼠的脾细胞应答(D)CD1小鼠的肝内淋巴细胞应答。通过将每只小鼠分别肌内注射4x107 IU和5x107 IU的ChAdOx2-SIi-HBV-CPmutS疫苗而给BALB/c小鼠(4只7周龄的小鼠)和CD1(2只18周龄的小鼠和5只13周龄的小鼠)接种疫苗。接种疫苗后14天,将小鼠处死,根据标准方案从脾脏和肝脏分离脾细胞和肝内淋巴细胞(IHL)。将2x105脾细胞和1x105 IHL与DMSO(1%)或非HBV肽库(A、I、L浓度为3μg/ml)或HBV肽库(核心、Pol-1、Pol-2、Pol-3、Pol-4、PreS1/S2和表面的浓度为3μg/ml)或阳性对照有丝分裂原(PHA或刀豆球蛋白A的浓度分别为10μg/ml和12.5μg/ml)一起平铺在ELSIPOT平板(通过过夜温育预先涂有抗小鼠INFγ单克隆抗体)上。在37℃过夜温育15小时后,将平板用PBS洗涤7次,并在室温下与生物素结合的小鼠抗INFγ温育2小时,然后用PBS和AP结合的抗生物素洗涤4次,在室温下温育2小时。然后将平板用PBS洗涤4次,并用BCIP/NBT底物显影,直到孔上出现斑点。最后用水洗涤并干燥后,在自动ELISpot读板仪(ELISpotplate reader)上对每个孔中每百万个细胞的斑点形成单位(SFU)进行计数。在单独的图表中显示了来自BALB/c和CD1小鼠的脾细胞和IHL对每种肽库刺激的ELISPOT应答。通过将对全部HBV肽库(核心、Pol-1、Pol-2、Pol-3、Pol-4、PreS1/S2和表面)的ELISPOT应答组合,还可以计算出来自HBV肽刺激的总应答。
图4:具有和不具有鲨鱼不变链(SIi)的HBV免疫原SIi-HBV-CPmutS的免疫原性的比较。(A)HBV-CPmutS免疫原布局。通过缺失存在于SIi-HBV-CPmutS中的SIi和第一接头来产生免疫原性HBV-CPmutS。HBV-CPmutS具有完全相同的氨基酸,只是它缺少存在于SIi-HBV-CPmutS免疫原中的SIi和第一接头序列。(B)CD1小鼠中的脾细胞应答。(C)CD1小鼠中的肝内淋巴细胞应答。如前所述产生ChAdOX2-HBV-CPmutS,并通过将每只小鼠肌内注射5x107IU的ChAdOx2-HBV-CPmutS疫苗而给CD1小鼠(10只7周龄的小鼠)接种疫苗,如前所述,接种疫苗后14天将小鼠处死,并产生了脾细胞和肝内淋巴细胞应答数据。将来自分别接种疫苗ChAdOx2-SIi-HBV-CPmutS和ChAdOx2-HBV-CPmutS的5只和10只CD1小鼠的数据进行比较,并在图表中表示以方便比较。
图5A:SIi-HBV-CPmutPreS-S(sh)的示意布局。
图5B:SIi-HBV-CPmutPreS-TPA-S(sh)的示意布局。
图6A:MVA-SIi-HBV-PreS-Pmut-C-S(sh)的示意布局。
图6B:MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh)的示意布局。
图7:在BALB/c小鼠中测试ChAdOx1-SIi-HBV-CPmutS疫苗,脾细胞应答:通过将每只小鼠肌内注射5x107 IU的ChAdOx1-SIi-HBV-CPmutS疫苗而给BALB/c小鼠(8只8周龄的小鼠)接种疫苗。如前所述,接种疫苗后14天将小鼠处死,并产生了脾细胞应答数据。条形图中表示了每个肽库刺激的脾细胞T细胞应答和全部HBV肽库的合并总应答。
图8:由ChAdOx1和ChAdOx2编码的HBV免疫原SIi-HBV-CPmutS的免疫原性的比较。如前所述(图2D),产生了编码ChAdOx1和ChAdOx2病毒载体疫苗的HBV-CPmutS免疫原。如前所述,通过将每只小鼠分别肌内注射5x107IU的ChAdOx2-HBV-CPmutS和ChAdOx1-HBV-CPmutS疫苗而给10只7周龄的CD1小鼠和8只8周龄的CD1小鼠接种疫苗,接种疫苗后14天将小鼠处死,并产生了脾细胞应答数据。将来自接种疫苗ChAdOx2-SIi-HBV-CPmutS和ChAdOx1-HBV-CPmutS的10只和8只CD1小鼠的数据进行比较,并在图表中表示以方便比较。与ChAdOx1-HBV-CPmutS疫苗相比,在接种疫苗ChAdOx2-HBV-CPmutS疫苗的小鼠中观察到总脾细胞T细胞应答具有统计学上显著更高的程度。
图9:使用短CMV启动子或长CMV启动子由ChAdOx1和ChAdOx2病毒载体编码的HBV免疫原SIi-HBV-CPmutPreS-S(sh)(称为HBV-v2)的免疫原性的比较。如前所述,产生了基于两个短CMV启动子和一个长CMV启动子的编码ChAdOx1(ChAdOx1-LP-HBV-v2和ChAdOx1-SP-HBV-v2)和ChAdOx2(ChAdOx2-SP-HBV-v2)疫苗的SIi-HBV-CPmutPreS-S(sh)免疫原(称为HBV-v2)。将15只8周龄的Balbc小鼠分为3组(每组5只小鼠),并通过肌内注射5x107 IU的ChAdOx1-SP-HBV-v2或ChAdOx2-SP-HBV-v2或ChAdOx1-LP-HBV-v2疫苗而接种疫苗。如前所述,接种疫苗后14天将小鼠处死,并产生了脾细胞应答数据。在同一图表中表示来自全部三种HBV-v2疫苗的比较数据以方便比较。与其它两种HBV-v2疫苗相比,在接种疫苗ChAdOx1-SP-HBV-v2疫苗的小鼠中观察到总脾细胞T细胞应答具有统计学上显著更高的程度。另外,与ChAdOx1-LP-HBV-v2疫苗相比,ChAdOx2-SP-HBV-v2疫苗在总脾细胞T细胞应答中显示出统计学上显著更高的程度。
图10A-G:显示了(A)SIi-HBV-CPmutS;(B)SIi-HBV-SCPmut(C)HBV-CPmutS(D)SIi-HBV-CPmutPreS-S(sh)(E)MVA-SIi-HBV-PreS-Pmut-CS(sh)(F)SIi-HBV-CPmutPreS-TPA-S(sh)和(G)MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh)的免疫原布局。
具体实施方式
基于HBV基因型C产生了HBV疫苗,HBV基因型C为东南亚最常见的HBV基因型之一,与慢性HBV感染的关联更为频繁。为了设计HBV免疫原,选择患者的HBV基因型C序列(GeneBank:KP017269.1),该序列最接近共有序列,这是通过比对乙型肝炎病毒数据库HBVdb的1447个HBV基因型C序列而产生的(图1A和1B)。与共有序列相比,所选的HBV基因型C序列只有三个核苷酸变化,其中两个是沉默突变,一个是聚合酶蛋白突变(图1C)。
据信,针对不同HBV蛋白的强大且具有多种抗原特异性的T细胞应答在解决HBV感染的病毒清除中起主要作用。基于该HBV免疫原已设计为编码病毒的所有主要蛋白,即核心(包括核心前区)、非功能性聚合酶Pmut(具有功能性突变的Pmut:HBV聚合酶旨在阻止疫苗编码的聚合酶参与HBV病毒复制的能力)和表面蛋白(包括其PreS1和PreS2区)。图2A和2B分别显示了HBV基因组的密码子布局和前两种HBV疫苗免疫原设计的示意图。该布局已设计为使用弗林蛋白酶2A(F2A)肽切割机制将前核心、核心和Pmut编码为融合蛋白和单独的表面蛋白,该机制通过导致核糖体跳跃事件而有助于从单个开放阅读框架编码两种蛋白。
在单个转基因盒中编码多个蛋白需要仔细设计,其中,密码子序列与CMV启动子的接近程度在编码蛋白的表达水平中起着重要作用。为了分析这两种免疫原(图2B)(SIi-HBV-CPmutS和SIi-HBV-SCPmut),我们产生了分别在免疫原盒的末端或开始编码表面蛋白的蛋白,并在蛋白印迹表达研究中对其进行了测试。蛋白印迹表达分析显示了布局SIi-HBV-CPmutS具有最佳的F2A切割可能性,当与SIi-HBV-SCPmut相比时,该布局产生了大量预期的CPmut和S蛋白(图2c)。
基于该观察,我们决定采用SIi-HBV-CPmutS免疫原布局以产生基于黑猩猩腺病毒(ChAdOx2)的T细胞诱导HBV疫苗(图2D)。按照良好的制造规范,在牛津大学詹纳研究所的病毒载体核心设施中制造了小批量的ChAdOx2-SIi-HBV-CPmutS,并用于小鼠免疫原性研究。
使用幼稚小鼠模型测试了ChAdOx2-SIi-HBV-CPmutS疫苗产生T细胞免疫应答的能力。通过将每只小鼠分别肌内注射4x107 IU和5x107 IU的ChAdOx2-SIi-HBV-CPmutS疫苗而对幼稚BALB/c小鼠和CD1小鼠进行免疫。接种疫苗后14天将小鼠处死,并用从脾脏和肝脏分离出脾细胞和肝内淋巴细胞(IHL)进行IFN-γELISPOT分析。将整个SIi-HBV-CPmutS免疫原中产生的15聚体合成肽(重叠11个氨基酸)组合成特异性库(表示SIi-HBV-CPmutS免疫原的不同区)并用作IFN-γELISPOT测定中的兴奋剂。结果显示ChAdOx2-SIi-HBV-CPmutS疫苗对SIi-HBV-CPmutS免疫原产生了良好的IFN-γELISPOT应答(图3)。BALB/c和CD1小鼠在免疫原中均显示出对聚合酶和表面蛋白应答较强、对核心蛋白应答较弱以及对非HBV蛋白(鲨鱼不变链[SIi]、F2A和接头)应答可忽略或无应答。
先前的研究已经显示了当放在免疫原的N末端时,鲨鱼不变链(SIi)可作为分子佐剂起作用,并增加对免疫原的总体T细胞免疫应答。为了对此进行测试,我们产生了没有SIi的HBV免疫原(HBV-CPmutS疫苗)(图4A),然后产生了ChAdOx2-HBV-CPmutS疫苗,并在类似的CD1小鼠免疫原性实验中对其进行了测试。结果显示与非SIi疫苗(ChAdOx2-HBV-CPmutS)相比,SIi疫苗(ChAdOx2-SIi-HBV-CPmutS)产生更高程度的IFN-γELISPOT应答(脾细胞和肝内淋巴细胞IFN-γELISPOT应答,如图4B、4C所示)。
病毒载体HBV疫苗设计的主要目的是产生针对HBV免疫原的T细胞和抗体应答。为了产生成功的抗体应答,该免疫原编码的蛋白必须折叠成其天然构象。为此,HBV免疫原(SIi-HBV-CPmutPreS-S(sh)和SIi-HBV-CPmutPreS-TPA-S(sh))被设计(图5A和5B),该免疫原编码用接头融合至表面蛋白S结构域的PreS1结构域的N末端的一半,可作为抗体诱导免疫原组分,并将表面蛋白的剩余肽序列(PreS1结构域的C末端的一半和整个PreS2结构域)融合至前核心/核心/Pmut以便保留产生T细胞免疫应答所需的T细胞表位。图5A和5B显示了SIi-HBV-CPmutPreS-S(sh)的示意布局。
还设计了MVA-HBV免疫原,其设计按照类似于SIi-HBV-CPmutPreS-S(sh)和SIi-HBV-CPmutPreS-TPA-S(sh)设计。然而,HBV免疫原SIi-HBV-CPmutPreS的T细胞组分由早期启动子F11编码,并且抗体诱导组分S(sh)或TPA-S(sh)由早期/晚期启动子mH5编码。克隆盒还具有F11左侧翼序列和F11右侧翼序列以允许通过同源重组插入到F11基因座中。图6A和6B分别显示了MVA-SIi-HBV-PreS-Pmut-C-S(sh)和MVA-SIi-HBV-CPmutPreS-TPA-S(sh)的示意布局。
结论:基于新颖的多抗原HBV免疫原的ChAdOx2-SIi-HBV-CPmutS在幼稚小鼠模型中具有高度免疫原性。这些研究为将来在慢性HBV小鼠模型中的研究铺平了道路,以评估其通过免疫治疗方法克服慢性HBV感染的能力。
序列:
由1447个基因型C序列(3215个碱基对)产生的HBV基因型C共有序列如SEQ ID NO:1所提供。KP017269.1HBV分离株JP-02的序列如SEQ ID NO:2所提供。
示例盒
1.SIi-HBV-CPmutS
1.1.SIi-HBV-CPmutS:免疫原布局如图10A所示
1.2.SIi-HBV-CPmutS:氨基酸序列(SEQ ID NO:3)
MSLLWGGVTVLAAMLIAGQVASVVFLVKGGGPGGGMQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQCGGGSGGGMPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLVGSSGLPRYVARLSSTSRNINYQHGTMQDLHDSCSRNLYVSLLLLYKTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPPRKRRAPVKQTLNFDLLKLAGDVESNPGPMGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNMENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI
1.3.SIi-HBV-CPmutS:HBV免疫原的氨基酸序列说明
1.3.1.多肽的第一个氨基酸=M
1.3.2.鲨鱼不变链(SIi)=SLLWGGVTVLAAMLIAGQVASVVFLV(SEQ IDNO:4)
1.3.3.接头=KGGGPGGG(SEQ ID NO:5)
1.3.4.C=
1.3.4.1.PreC=
MQLFHLCLIISCSCPTVQASKLCLGWLWG(SEQ ID NO:16)
1.3.4.2.核心=
MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC(SEQ ID NO:6)
1.3.5.接头=GGGSGGG(SEQ ID NO:7)
1.3.6.Pmut=(突变:Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A)
MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP(SEQ ID NO:8)
1.3.7.弗林蛋白酶2A(F2A)=RKRRAPVKQTLNFDLLKLAGDVESNPGP(SEQ ID NO:9)
1.3.8.表面蛋白(S)=
1.3.8.1.PreS1=
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQA(SEQ ID NO:52)
1.3.8.2.PreS2=
MQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN(SEQID NO:53)
1.3.8.3.表面(S)=
MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI(SEQ ID NO:10)
SIi-HBV-CPmutS核苷酸序列如SEQ ID NO:46所提供。
2.SIi-HBV-SCPmut
2.1.SIi-HBV-SCPmut:免疫原布局如图10B所示
2.2.SIi_HBV-SCPmut:氨基酸序列(SEQ ID NO:11)
MSLLWGGVTVLAAMLIAGQVASVVFLVKGGSMGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNMENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYIRKRRAPVKQTLNFDLLKLAGDVE SNPGPMQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQCGGGSGGGMPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLVGSSGLPRYVARLSSTSRNINYQHGTMQDLHDSCSRNLYVSLLLLYKTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP
2.3.SIi-HBV-SCPmut:HBV免疫原的氨基酸序列说明
2.3.1.多肽的第一个氨基酸=M
2.3.2.鲨鱼不变链(SIi)=SLLWGGVTVLAAMLIAGQVASVVFLV(SEQ IDNO:4)
2.3.3.接头=KGGS(SEQ ID NO:14)
2.3.4.表面蛋白(S)=
2.3.4.1.PreS1=
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQA(SEQ ID NO:52)
2.3.4.2.PreS2=
MQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN(SEQID NO:53)
2.3.4.3.表面(S)=
MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI(SEQ ID NO:10)
2.3.5.弗林蛋白酶2A(F2A)=RKRRAPVKQTLNFDLLKLAGDVESNPGP(SEQ ID NO:9)
2.3.6.C=
2.3.6.1.前核心=
MQLFHLCLIISCSCPTVQASKLCLGWLWG(SEQ ID NO:16)
2.3.6.2.核心=
MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC(SEQ ID NO:6)
2.3.7.接头=GGGSGGG(SEQ ID NO:7)
2.3.8.Pmut=(突变:Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A)
MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP(SEQ ID NO:8)
SIi-HBV-SCPmut核苷酸序列如SEQ ID NO:47所提供。
3.HBV-CPmutS
3.1.HBV-CPmutS:免疫原布局如图10C所示
3.2.HBV-CPmutS:氨基酸序列(SEQ ID NO:12)
MQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQCGGGSGGGMPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLVGSSGLPRYVARLSSTSRNINYQHGTMQDLHDSCSRNLYVSLLLLYKTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPPRKRRAPVK QTLNFDLLKLAGDVESNPGPMGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNMENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI
3.3.HBV-CPmutS:HBV免疫原的氨基酸序列说明
3.3.1.C=
3.3.1.1.前核心=
MQLFHLCLIISCSCPTVQASKLCLGWLWG(SEQ ID NO:16)
3.3.1.2核心=
MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC(SEQ ID NO:6)
3.3.2.接头=GGGSGGG(SEQ ID NO:7)
3.3.3.Pmut=(突变:Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A)
MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP(SEQ ID NO:8)
3.3.4.弗林蛋白酶2A(F2A)=RKRRAPVKQTLNFDLLKLAGDVESNPGP(SEQ ID NO:9)
3.3.5.表面蛋白(S)=
3.3.5.1PreS1=
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQA(SEQ ID NO:52)
3.3.5.2PreS2=
MQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN(SEQID NO:53)
3.3.5.3表面(S)
MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI(SEQ ID NO:10)
4.SIi-HBV-CPmutPreS-S(sh)
4.1SIi-HBV-CPmutPreS-S(sh):免疫原布局如图10D所示
4.2SIi-HBV-CPmutPreS-S(sh):氨基酸序列(SEQ ID NO:13)
MSLLWGGVTVLAAMLIAGQVASVVFLVKGGGPGGGMQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQCGGGSGGGMPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPPKSPNSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNGSKGKRKRRAPVKQTLNFDLLKLAGDVESNPGPMGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGLEGGSGGMENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI
4.3SIi-HBV-CPmutPreS-S(sh):HBV免疫原的氨基酸序列说明
4.3.1.多肽的第一个氨基酸=M
4.3.2.鲨鱼不变链(SIi)=SLLWGGVTVLAAMLIAGQVASVVFLV(SEQ IDNO:4)
4.3.3.接头=KGGGPGGG(SEQ ID NO:5)
4.3.4.C=
4.3.4.1前核心=
MQLFHLCLIISCSCPTVQASKLCLGWLWG(SEQ ID NO:16)
4.3.4.2核心=
MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC((SEQ ID NO:6)
4.3.5.接头=GGGSGGG(SEQ ID NO:7)
4.3.6.Pmut=(突变:Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A)
MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP(SEQ ID NO:8)
4.3.7.接头=KSP
4.3.8.NΔPreS1和PreS2=
NSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN(SEQ IDNO:15)
4.3.9.接头=GSKGK(SEQ ID NO:20)
4.3.10.弗林蛋白酶2A(F2A)=RKRRAPVKQTLNFDLLKLAGDVESNPGP(SEQ ID NO:9)
4.3.11.S(sh)=
4.3.11.1.CΔPreS1=
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHDHWPEANQVG(SEQ IDNO:21)
4.3.11.2.接头=LEGGSGG(SEQ ID NO:22)
4.3.11.3.表面(S)=
MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI(SEQ ID NO:18)
SIi-HBV-CPmutPreS-S(sh)核苷酸序列如SEQ ID NO:48所提供。
5.MVA-SIi-HBV-PreS-Pmut-C-S(sh)
5.1.MVA-SIi-HBV-PreS-Pmut-C-S(sh):免疫原布局如图10E所示
5.2.MVA-SIi-HBV-PreS-Pmut-C-S(sh):氨基酸序列(SEQ ID NO:23)
MSLLWGGVTVLAAMLIAGQVASVVFLVSKSGPPSGKSNSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNGSKSGSKMPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLVGSSGLPRYVARLSSTSRNINYQHGTMQDLHDSCSRNLYVSLLLLYKTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPPSKSPGSGPPMQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGASKGGKSGMENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI
5.3.MVA-SIi-HBV-PreS-Pmut-C-S(sh):HBV免疫原的氨基酸序列说明
5.3.1.1.多肽的第一个氨基酸=M
5.3.1.2.鲨鱼不变链(SIi)=SLLWGGVTVLAAMLIAGQVASVVFLV(SEQID NO:4)
5.3.1.3.接头=SKSGPPSGKS(SEQ ID NO:31)
5.3.1.4.NΔPreS1和PreS2=
NSNNPDWDFNPNKDHDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN(SEQID NO:15)
5.3.1.5.接头=GSKSGSK(SEQ ID NO:32)
5.3.1.6.Pmut=(突变:Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A)
MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP(SEQ ID NO:8)
5.3.1.7.接头=SKSPGSGPP(SEQ ID NO:33)
5.3.1.8.C=
5.3.1.8.1.前核心
MQLFHLCLIISCSCPTVQASKLCLGWLWG(SEQ ID NO:16)
5.3.1.8.2.核心=
MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC(SEQ ID NO:6)
5.3.1.9.S(sh)
5.3.1.9.1.CΔPreS1=
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVG
5.3.1.9.2.接头=
ASKGGKSG(SEQ ID NO:34)
5.3.1.9.3.表面=
MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI(SEQ ID NO:18)
5.4.MVA-SIi-HBV-PreS-Pmut-C-S(sh)的核苷酸序列如SEQ ID NO:24所提供。
5.5.MVA-SIi-HBV-PreS-Pmut-C-S(sh)核苷酸序列的说明:
5.5.1.F11-L-侧翼=碱基1-1097(SEQ ID NO:35)
5.5.2.SIi-HBV-PreS-Pmut-C=碱基1098-4838(SEQ ID NO:37)
5.5.3.转录终止子序列=碱基4839-4845
TTTTGT
5.5.4.mH5启动子=碱基4846-4942(SEQ ID NO:28)
5.5.5.S(sh)=碱基4943-5824(SEQ ID NO:38)
5.5.6.F11-R-侧翼=碱基5582-7143(SEQ ID NO:36)
6.SIi-HBV-CPmutPreS-TPA-S(sh)
6.1.SIi-HBV-CPmutPreS-TPA-S(sh):免疫原布局如图10F所示
6.2.SIi-HBV-CPmutPreS-TPA-S(sh):氨基酸序列(SEQ ID NO:25)
MSLLWGGVTVLAAMLIAGQVASVVFLVKGGGPGGGMQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQCGGGSGGGMPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPPKSPNSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNGSKGKRKRRAPVKQTLNFDLLKLAGDVESNPGPMDAMKRGLCCVLLLCGAVFVSPSQ EIHARFRRMGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGLEGGSGGMENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI
6.3.SIi-HBV-CPmutPreS-TPA-S(sh):HBV免疫原的氨基酸序列说明
6.3.1.多肽的第一个氨基酸=M
6.3.2.鲨鱼不变链(SIi)=SLLWGGVTVLAAMLIAGQVASVVFLV(SEQ IDNO:4)
6.3.3.接头=KGGGPGGG(SEQ ID NO:5)
6.3.4.C=
6.3.4.1.前核心
MQLFHLCLIISCSCPTVQASKLCLGWLWG(SEQ ID NO:16)
6.3.4.2.核心=
MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC(SEQ ID NO:6)
6.3.5.接头=GGGSGGG(SEQ ID NO:7)
6.3.6.Pmut=(突变:Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A)
MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP(SEQ ID NO:8)
6.3.7.接头=KSP
6.3.8.NΔPreS1和PreS2=
NSNNPDWDFNPNKDHDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN(SEQID NO:15)
6.3.9.接头=GSKGK(SEQ ID NO:20)
6.3.10.弗林蛋白酶2A(F2A)=RKRRAPVKQTLNFDLLKLAGDVESNPGP(SEQ ID NO:9)
6.3.11.TPA=MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRR(SEQ ID NO:30)
6.3.12.S(sh)=
6.3.12.1.CΔPreS1=
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHDHWPEANQVG(SEQ IDNO:21)
6.3.12.2.接头=LEGGSGG(SEQ ID NO:22)
6.3.12.3.表面(S)=
MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI(SEQ ID NO:18)
SIi-HBV-CPmutPreS-TPA-S(sh)核苷酸序列如SEQ ID NO:49所提供。
7.MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh)
7.1.MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh):免疫原布局如图10G所示
7.2.MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh):氨基酸序列(SEQ ID NO:26)
MSLLWGGVTVLAAMLIAGQVASVVFLVSKSGPPSGKSNSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPNGSKSGSKMPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSWLSLDVSAAFYHIPLHPAAMPHLLVGSSGLPRYVARLSSTSRNINYQHGTMQDLHDSCSRNLYVSLLLLYKTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPPSKSPGSGPPMQLFHLCLIISCSCPTVQASKLCLGWLWGMDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQCMDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRMGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGASKGGKSGMENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI
7.3.MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh):HBV免疫原的氨基酸序列说明
7.3.1.1.多肽的第一个氨基酸=M
7.3.1.2.鲨鱼不变链(SIi)=SLLWGGVTVLAAMLIAGQVASVVFLV(SEQID NO:4)
7.3.1.3.接头=SKSGPPSGKS(SEQ ID NO:31)
7.3.1.4.NΔPreS1和PreS2=
NSNNPDWDFNPNKDHDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQAMQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN(SEQID NO:15)
7.3.1.5.接头=GSKSGSK(SEQ ID NO:32)
7.3.1.6.Pmut=(突变:Y63A、C323A、C334A、C338A、C352A、R714A、D788A、R792A)
MPLSYQHFRKLLLLDDEAGPLEEELPRLADEGLNRRVAEDLNLGNLNVSIPWTHKVGNFTGLASSTVPVFNPEWQTPSFPHIHLQEDIINRCQQYVGPLTVNEKRRLKLIMPARFYPNLTKYLPLDKGIKPYYPEHAVNHYFKTRHYLHTLWKAGILYKRETTRSASFCGSPYSWEQELQHGRLVFQTSTRHGDESFCSQSSGILSRSPVGPCVRSQLKQSRLGLQPQQGSLARGKSGRSGSIRARVHPTTRRSFGVEPSGSGHIDNSASSTSSCLHQSAVRKTAYSHLSTSKRQSSSGHAVELHNIPPSSARSQSEGPIFSAWWLQFRNSKPASDYALTHIVNLLEDWGPATEHGEHNIRIPRTPARVTGGVFLVDKNPHNTTESRLVVDFSQFSRGSTHVSWPKFAVPNLQSLTNLLSSNLSTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMDDVVLGAKSVQHLESLFTSITNFLLSLGIHLNPNKTKRWGYSLNFMGYVIGSWGTLPQEHIVLKIKQCFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSPTYKAFLCKQYLNLYPVARQRSGLCQVFADATPTGWGLAIGHRAMRGTFVAPLPIHTAELLAACFARSRSGAKLIGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPAADPSAGRLGLYRPLLHLPFRPTTGRTSLYAVSPSVPSHLPDRVHFASPLHVAWRPP(SEQ ID NO:8)
7.3.1.7.接头=SKSPGSGPP(SEQ ID NO:33)
7.3.1.8.C=
7.3.1.8.1.前核心=
MQLFHLCLIISCSCPTVQASKLCLGWLWG(SEQ ID NO:16)
7.3.1.8.2.核心=
MDIDPYKEFGASVELLSFLPSDFFPSIRDLLDTASALYREALESPEHCSPHHTALRQAILCWGELMNLATWVGSNLEDPASRELVVSYVNVNMGLKIRQLLWFHISCLTFGRETVLEYLVSFGVWIRTPPAYRPPNAPILSTLPETTVVRRRGRSPRRRTPSPRRRRSQSPRRRRSQSRESQC(SEQ ID NO:6)
7.3.1.9.TPA=MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRR(SEQ ID NO:30)
7.3.1.10.S(sh)_=
7.3.1.10.1.CΔPreS1=
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHDHWPEANQVG(SEQ IDNO:21)
7.3.1.10.2.接头=ASKGGKSG(SEQ ID NO:34)
7.3.1.10.3.表面(S)=
MENTTSGFLGPLLVLQAGFFLLTRILTIPQSLDSWWTSLNFLGGAPTCPGQNSQSPTSNHSPTSCPPICPGYRWMCLRRFIIFLFILLLCLIFLLVLLDYQGMLPVCPLLPGTSTTSTGPCKTCTIPAQGTSMFPSCCCTKPSDGNCTCIPIPSSWAFARFLWEWASVRFSWLSLLVPFVQWFVGLSPTVWLSVIWMMWYWGPSLYNILSPFLPLLPIFFCLWVYI(SEQ ID NO:18)
7.4.MVA-Sli-HBV-PreS-Pmut-C-TPA-S(sh)的核苷酸序列如SEQ ID NO:27所提供。
7.5.MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh)核苷酸序列的说明:
7.5.1.F11-L-侧翼=碱基1-1097(SEQ ID NO:35)
7.5.2.SIi-HBV-PreS-Pmut-C=碱基1098-4838(SEQ ID NO:37)
7.5.3.转录终止子序列=碱基4839-4845
TTTTGT
7.5.4.mH5启动子=碱基4846-4942(SEQ ID NO:28)
7.5.5.TPA=碱基4943-5038(SEQ ID NO:29)
7.5.6.S(sh)=碱基5039-5920(SEQ ID NO:38)
7.5.7.F11-R-侧翼=碱基5921-7239(SEQ ID NO:36)
8.低GC含量形式MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh)的核苷酸序列(SEQ IDNO:58):
gtaatctattcgatataccgttgctaacagtatactggcccaataactgtggatggaaaatctataataatacattaatatcatccgatggtgctagggttatttggatggatgcgtataaattttcttgcggtttatctttacaagactattgttatcattggggtagcaaaccagagagccgaccattcgatttaataaaaaaatcagatgctaaacgcaattctaaatcgttggtcaaagaatctatggcatccttgaaatccttgtacgaggcattcgagacacaatcaggagcgttagaagttttaatgagtccatgtaggatgttttcgttttctagaatagaagacatgttcttaactagtgtcattaatagagtatccgagaatactggaatggggatgtattatcctaccaacgatataccttctctatttatcgaatcatctatctgtctagattatattatagtaaataatcaggaatccaacaaatatcgtatcaaatctgttctcgatatcatttcttcaaaacaataccctgcaggacgtcccaactacgttaaaaatggtacaaaaggaaagttatatatcgcgttgtgtaaagttaccgtacctactaacgaccatattccagtagtttatcacgatgatgacaatactaccacctttattacagtattgacgtccgtcgatattgaaactgctatcagagcaggatattcgatagtcgaattaggggctttacaatgggataataatattccagaacttaaaaacggtttactggatagtatcaagatgatttatgacttgaacgcagttacaacaaataatttattggaacagctcatagaaaatattaactttaacaactctagtataatttcgttgttttatacatttgccattagttattgccgagcattcatttactcaattatggaaaccatagatccggtgtatatatctcagttcagttataaagaattatacgttagtagctcttataaagatattaatgaatccatgagtcagatggtaaaattataaaaagtgaaaaacaatattatttttatcgttggttgttacactATGTCACTTCTTTGGGGCGGAGTTACAGTTCTTGCTGCTATGCTTATTGCTGGACAAGTTGCTTCTGTTGTGTTTCTTGTTTCTAAATCTGGACCTCCTTCTGGAAAATCTAATTCTAACAATCCTGATTGGGATTTCAATCCTAACAAAGATCATTGGCCTGAAGCTAATCAAGTTGGAGCTGGTGCTTTTGGACCTGGTTTTACACCTCCTCATGGTGGATTGCTTGGATGGTCACCTCAAGCTCAGGGAATTCTTACAACAGTTCCAGCTGCTCCTCCTCCTGCTTCTACAAATAGACAATCTGGTAGACAACCTACACCTATTTCTCCACCTCTTAGAGATTCTCATCCTCAAGCTATGCAATGGAATTCTACTACATTTCATCAAGCTTTGCTTGATCCTAGAGTTAGAGGACTTTATTTTCCTGCTGGTGGAAGTTCTTCTGGAACAGTTAATCCTGTTCCTACAACAGCTTCTCCAATTTCTTCTATATTTTCTAGAACAGGCGATCCTGCTCCTAATGGATCAAAATCTGGATCAAAAATGCCTCTGTCTTATCAACACTTTAGAAAATTGCTGCTTCTTGATGATGAAGCTGGACCTCTTGAAGAAGAATTGCCTAGACTTGCTGATGAAGGACTTAATAGAAGAGTTGCTGAAGATCTTAATCTGGGAAATCTTAATGTTTCTATTCCTTGGACACACAAAGTTGGAAATTTCACAGGACTTGCATCTTCTACAGTGCCTGTTTTTAATCCTGAATGGCAAACACCTTCTTTTCCACATATTCATCTGCAAGAGGATATCATCAATAGATGTCAACAATATGTTGGACCACTGACAGTTAATGAGAAGAGAAGGCTTAAACTTATTATGCCTGCTAGATTCTATCCTAATCTTACAAAGTATTTGCCTCTGGATAAGGGAATCAAACCTTATTATCCTGAACATGCTGTGAATCACTACTTTAAAACAAGACATTATCTGCATACACTGTGGAAAGCTGGTATTCTTTACAAAAGAGAAACAACAAGATCTGCTTCATTTTGTGGATCTCCATATTCTTGGGAACAAGAACTTCAACATGGTAGACTTGTTTTTCAAACATCTACAAGACATGGGGATGAATCATTTTGTTCTCAAAGTTCTGGAATTCTTTCTAGATCTCCTGTTGGACCTTGTGTTAGATCTCAACTTAAACAATCTAGACTTGGACTTCAACCTCAACAAGGATCTCTTGCTAGAGGAAAAAGTGGAAGATCTGGATCTATTAGAGCTAGAGTTCATCCTACAACTAGAAGATCTTTTGGAGTTGAACCTTCTGGATCTGGACATATTGATAATTCTGCCTCTTCTACATCTTCTTGTCTGCATCAATCTGCTGTTAGAAAGACAGCTTATTCTCATTTGTCTACTTCTAAGAGACAATCATCTTCTGGACATGCTGTTGAACTTCATAATATTCCTCCAAGTAGTGCTAGAAGTCAATCTGAAGGACCAATATTTTCAGCTTGGTGGCTTCAATTCAGAAATTCTAAACCTGCTTCTGATTATGCTCTGACACATATAGTTAATTTGCTTGAAGATTGGGGACCTGCTACAGAACATGGCGAACACAATATTAGAATACCTAGAACTCCTGCTAGAGTTACAGGCGGAGTCTTTTTGGTTGATAAGAATCCTCATAATACCACAGAATCAAGACTTGTTGTTGATTTTTCACAGTTTTCTAGAGGATCTACACATGTTTCTTGGCCTAAATTTGCTGTTCCAAATCTTCAATCTCTTACAAATTTGCTTTCATCTAATCTTTCTTGGCTGTCTCTTGATGTTTCTGCTGCCTTTTATCATATTCCTCTTCATCCTGCTGCAATGCCTCATTTGCTTGTTGGATCATCTGGACTTCCAAGATATGTTGCTAGACTTAGCTCTACATCTAGAAATATCAATTATCAGCATGGAACAATGCAGGATCTTCACGATTCTTGTAGTAGGAATCTGTATGTTTCTTTGCTTCTGCTGTATAAGACATTTGGAAGAAAACTTCATCTGTATTCTCACCCTATTATTCTGGGTTTTAGAAAGATTCCTATGGGAGTTGGACTTTCTCCTTTTTTGCTTGCTCAATTCACATCTGCTATTTGTTCTGTTGTTAGAAGGGCTTTTCCTCATTGTCTTGCATTTTCTTATATGGATGATGTTGTTCTTGGAGCTAAATCTGTTCAACATCTTGAAAGTCTGTTTACCTCTATTACTAATTTTCTGCTTTCTCTGGGAATTCATCTGAATCCAAACAAAACAAAGAGATGGGGATATTCTCTTAATTTCATGGGATATGTTATTGGATCTTGGGGAACACTTCCTCAAGAACATATCGTTTTGAAAATCAAGCAATGTTTCAGAAAACTGCCTGTGAATAGACCTATTGATTGGAAAGTTTGTCAAAGAATTGTGGGACTTCTTGGATTTGCTGCTCCTTTTACACAATGTGGATATCCTGCTCTTATGCCACTTTATGCTTGTATTCAATCTAAACAGGCTTTTACATTTTCTCCAACATACAAAGCTTTTCTGTGTAAACAGTATCTGAATCTTTATCCTGTGGCTAGACAAAGATCTGGTCTTTGTCAAGTTTTTGCTGATGCTACACCAACAGGATGGGGACTTGCTATTGGACATAGAGCTATGAGAGGAACATTTGTTGCTCCATTGCCTATTCATACAGCTGAATTGCTTGCTGCTTGTTTTGCTAGATCTAGAAGCGGAGCAAAACTTATTGGTACAGATAATAGTGTTGTCCTGAGTAGAAAGTACACATCTTTTCCATGGTTGTTGGGATGTGCTGCTAATTGGATTCTTAGAGGAACTTCTTTTGTTTATGTTCCTTCTGCTCTTAATCCTGCAGCTGATCCATCTGCTGGTAGATTGGGACTGTATAGACCACTTCTTCATTTGCCTTTTAGACCAACAACTGGAAGAACATCTCTTTATGCTGTTTCTCCTTCTGTTCCATCTCATTTGCCTGATAGAGTTCATTTTGCTTCTCCACTTCATGTTGCTTGGAGGCCACCATCTAAATCTCCAGGTTCTGGACCACCTATGCAACTTTTTCATTTGTGTTTGATCATTAGCTGTTCTTGTCCTACAGTTCAAGCTTCTAAACTTTGTCTTGGATGGCTTTGGGGAATGGATATTGATCCATACAAAGAATTTGGAGCTAGTGTTGAATTGCTGTCATTTCTTCCATCTGATTTTTTCCCTTCTATTCGTGATCTTCTTGATACAGCATCTGCTCTGTATAGAGAAGCTCTTGAATCTCCTGAACACTGTTCTCCACATCATACAGCACTTAGACAAGCTATTCTTTGTTGGGGAGAACTTATGAATCTTGCTACATGGGTTGGATCTAATTTGGAAGATCCAGCTTCTAGAGAATTGGTGGTTTCTTATGTTAATGTGAATATGGGACTGAAAATTAGACAACTGCTTTGGTTTCATATCTCTTGTCTTACATTTGGTAGAGAAACAGTTTTGGAATATTTGGTTTCTTTTGGCGTTTGGATTAGAACACCTCCAGCTTATAGACCTCCTAATGCTCCTATTTTGTCTACACTTCCTGAAACAACAGTCGTTAGAAGAAGAGGAAGATCTCCAAGAAGAAGAACACCAAGTCCTAGAAGAAGAAGATCTCAATCACCAAGAAGAAGAAGAAGTCAATCTAGAGAATCTCAATGTTGATTTTTGTTCGACATTAAAAATTGAAAATAAATACAAAGGTTCTTGAGGGTTGTGTTAAATTGAAAGCGAGAAATAATCATAAATATGATTCAGGTGACGGATCCATGGATGCTATGAAGCGAGGACTTTGTTGTGTTTTGCTTCTTTGTGGTGCTGTGTTTGTTTCTCCATCTCAAGAAATTCATGCCAGATTCAGAAGAATGGGAGGCTGGTCATCTAAACCTAGACAAGGCATGGGAACAAATCTTTCTGTTCCTAATCCTTTGGGATTCTTTCCTGATCATCAATTGGATCCAGCATTTGGAGCAAATAGTAACAATCCAGATTGGGACTTTAACCCAAACAAAGATCATTGGCCAGAAGCTAATCAAGTTGGAGCATCTAAAGGTGGAAAAAGTGGAATGGAAAACACTACATCTGGATTTCTTGGACCTTTGCTTGTTCTTCAAGCTGGATTTTTCCTGTTGACAAGAATACTTACAATTCCTCAATCACTGGATTCTTGGTGGACAAGTCTTAATTTTCTTGGAGGTGCTCCTACATGTCCTGGACAAAATTCTCAATCTCCAACTTCTAATCATTCTCCTACATCTTGTCCTCCAATTTGTCCTGGATATAGATGGATGTGTCTTAGAAGATTCATTATCTTTCTTTTCATACTGCTGCTGTGTCTGATTTTCCTTCTTGTTTTGTTGGATTATCAGGGAATGCTTCCTGTTTGTCCTTTGCTTCCTGGAACTTCTACAACAAGTACAGGACCTTGTAAAACATGTACAATTCCAGCACAGGGAACATCTATGTTTCCAAGTTGTTGTTGTACAAAACCTTCTGATGGAAATTGCACATGTATTCCTATTCCAAGTTCTTGGGCATTTGCTAGATTTCTTTGGGAATGGGCTTCTGTTAGATTCAGTTGGTTGTCTCTTTTGGTTCCATTTGTTCAGTGGTTTGTTGGATTGTCTCCTACAGTTTGGCTTTCTGTTATTTGGATGATGTGGTATTGGGGACCTTCTCTTTACAATATTTTGAGTCCTTTTCTCCCTTTGCTGCCAATTTTCTTTTGTCTTTGGGTTTACATTTGAttaaccgagtttctgcattattgtaattcgtatgctggcaccatcaaagaatcacttctaaaagatatcaatatcacacatacaaatattactaccctattgaatgagacagccaaggttatcaagttagtaaaatctctggtagataaagaagatactgatattgtgaataatttcattaccaaagaaattaaaaacagagacaaaatagttaatagtttgtctctatcaaacctggactttcgtttgtaaattggggctTtttgtacaataaatgggtgttgccaatgattcatcccctgaatatcaatggatgtctccccatagattatcagatactgttatattaggagactgtttgtattttaacaatataatgtcccaattagatttacaccaaaattgggctccatcagttagattgttaaattattttaagaattttaataaggaaacactactaaagatagaagagaatgattacattaattcatcctttttccaacaaaaggataaacgattttatcctataaacgacgatttttatcacatatctacaggaggatatggtatagtctttaagatagataactatgtagtaaaatttgtattcgaggccacaaaattatatagtcccatggaaactacggcggagttcacagtacccaaatttctatacaacaatctaaagggagatgaaaaaaaattaatcgtgtgtgcgtgggccatgggattaaactataaattaacatttttacatactctgtataaacgtgttcttcatatgttgctattattgatacaaactatggatggtcaggaactatcattgagatattcttctaaagtttttttaaaggcgtttaacgagagaaaggacagtatcaaattcgtgaaattactatcccacttttatccggcagttattaacagtaatattaatgttataaactattttaaccgcatgtttcactttttcgaacatgaaaagagaactaactacgaatacgaaagaggaaatattataatttttcccctagcactgtattcggcagataaagtagataccgagctagctatcaaattaggatttaaatctttggtacaatacataaagtttatctttttacagatggctctgttatacattaaaatttacgaactaccatgctgcgcaacta
8.1低GC含量形式MVA-SIi-HBV-PreS-Pmut-C-S(sh)的核苷酸序列说明:
8.1.1F11-L-侧翼=碱基1-1097(SEQ ID NO:35)
8.1.2SIi-HBV-PreS-Pmut-C=碱基1098-4838(SEQ ID NO:59)
8.1.3转录终止子序列=碱基4839-4845
TTTTGT
8.1.4mH5启动子=碱基4846-4942(SEQ ID NO:28)
8.1.5TPA=碱基4943-5038(SEQ ID NO:60)
8.1.6S(sh)=碱基5039-5920(SEQ ID NO:61)
8.1.7F11-R-侧翼=5921-7239碱基(SEQ ID NO:36)
野生型HBV聚合酶的序列如SEQ ID NO:19所提供。
ChAdOx1序列
免疫原盒的ChAdOx1序列5'如SEQ ID NO:39所提供。免疫原盒的ChAdOx1序列3’如SEQ ID NO:40所提供。
ChAdOx2序列
免疫原盒的ChAdOx2序列5’如SEQ ID NO:41所提供。免疫原盒的ChAdOx2序列3’如SEQ ID NO:42所提供。
MVA序列
免疫原盒的MVA序列5’如SEQ ID NO:44所提供。免疫原盒的MVA序列3’如SEQ IDNO:45所提供。
具有Tetron操纵子序列的CMV长启动子如SEQ ID NO:50所提供。具有Tetron操纵子序列的CMV短启动子如SEQ ID NO:51所提供。
PreS1序列(SEQ ID NO:52):
MGGWSSKPRQGMGTNLSVPNPLGFFPDHQLDPAFGANSNNPDWDFNPNKDHWPEANQVGAGAFGPGFTPPHGGLLGWSPQAQGILTTVPAAPPPASTNRQSGRQPTPISPPLRDSHPQA
PreS2序列(SEQ ID NO:53):
MQWNSTTFHQALLDPRVRGLYFPAGGSSSGTVNPVPTTASPISSIFSRTGDPAPN
序列表
<110> 牛津大学创新有限公司
<120> HBV疫苗
<130> JDM86936P.WOP
<150> GB1705765.4
<151> 2017-04-10
<160> 61
<170> PatentIn version 3.5
<210> 1
<211> 3215
<212> DNA
<213> 乙型肝炎病毒
<400> 1
ctccacaaca ttccaccaag ctctgctaga tcccagagtg aggggcctat actttcctgc 60
tggtggctcc agttccggaa cagtaaaccc tgttccgact actgcctcac ccatatcgtc 120
aatcttctcg aggactgggg accctgcacc gaacatggag aacacaacat caggattcct 180
aggacccctg ctcgtgttac aggcggggtt tttcttgttg acaagaatcc tcacaatacc 240
acagagtcta gactcgtggt ggacttctct caattttcta gggggagcac ccacgtgtcc 300
tggccaaaat tcgcagtccc caacctccaa tcactcacca acctcttgtc ctccaatttg 360
tcctggctat cgctggatgt gtctgcggcg ttttatcata ttcctcttca tcctgctgct 420
atgcctcatc ttcttgttgg ttcttctgga ctaccaaggt atgttgcccg tttgtcctct 480
acttccagga acatcaacta ccagcacggg accatgcaag acctgcacga ttcctgctca 540
aggaacctct atgtttccct cttgttgctg tacaaaacct tcggacggaa actgcacttg 600
tattcccatc ccatcatcct gggctttcgc aagattccta tgggagtggg cctcagtccg 660
tttctcctgg ctcagtttac tagtgccatt tgttcagtgg ttcgtagggc tttcccccac 720
tgtttggctt tcagttatat ggatgatgtg gtattggggg ccaagtctgt acaacatctt 780
gagtcccttt ttacctctat taccaatttt cttttgtctt tgggtataca tttgaaccct 840
aataaaacca aacgttgggg ctactccctt aacttcatgg gatatgtaat tggaagttgg 900
ggtactttac cacaggaaca tattgtacta aaaatcaagc aatgttttcg aaaactgcct 960
gtaaatagac ctattgattg gaaagtatgt caaagaattg tgggtctttt gggctttgct 1020
gcccctttta cacaatgtgg ctatcctgcc ttaatgcctt tatatgcatg tatacaatct 1080
aagcaggctt tcactttctc gccaacttac aaggcctttc tgtgtaaaca atatctgaac 1140
ctttaccccg ttgcccggca acggtcaggt ctctgccaag tgtttgctga cgcaaccccc 1200
actggatggg gcttggccat aggccatcgg cgcatgcgtg gaacctttgt ggctcctctg 1260
ccgatccata ctgcggaact cctagcagct tgttttgctc gcagccggtc tggagcgaaa 1320
cttatcggaa ccgacaactc tgttgtcctc tctcggaaat acacctcctt tccatggctg 1380
ctagggtgtg ctgccaactg gatcctgcgc gggacgtcct ttgtctacgt cccgtcggcg 1440
ctgaatcccg cggacgaccc gtctcggggc cgtttgggac tctaccgtcc ccttcttcat 1500
ctgccgttcc ggccgaccac ggggcgcacc tctctttacg cggtctcccc gtctgtgcct 1560
tctcatctgc cggaccgtgt gcacttcgct tcacctctgc acgtcgcatg gagaccaccg 1620
tgaacgccca ccaggtcttg cccaaggtct tacataagag gactcttgga ctctcagcaa 1680
tgtcaacgac cgaccttgag gcatacttca aagactgttt gtttaaagac tgggaggagt 1740
tgggggagga gattaggtta atgatctttg tactaggagg ctgtaggcat aaattggtct 1800
gttcaccagc accatgcaac tttttcacct ctgcctaatc atctcatgtt catgtcctac 1860
tgttcaagcc tccaagctgt gccttgggtg gctttggggc atggacattg acccgtataa 1920
agaatttgga gcttctgtgg agttactctc ttttttgcct tctgacttct ttccttctat 1980
tcgagatctc ctcgacaccg cctctgctct gtatcgggag gccttagagt ctccggaaca 2040
ttgttcacct caccatacag cactcaggca agctattctg tgttggggtg agttgatgaa 2100
tctggccacc tgggtgggaa gtaatttgga agacccagca tccagggaat tagtagtcag 2160
ctatgtcaat gttaatatgg gcctaaaaat cagacaacta ttgtggtttc acatttcctg 2220
tcttactttt ggaagagaaa ctgttcttga gtatttggtg tcttttggag tgtggattcg 2280
cactcctccc gcttacagac caccaaatgc ccctatctta tcaacacttc cggaaactac 2340
tgttgttaga cgacgaggca ggtcccctag aagaagaact ccctcgcctc gcagacgaag 2400
gtctcaatcg ccgcgtcgca gaagatctca atctcgggaa tctcaatgtt agtatccctt 2460
ggactcataa ggtgggaaac tttactgggc tttattcttc tactgtacct gtctttaatc 2520
ctgagtggca aactccctcc tttcctcaca ttcatttaca ggaggacatt attaatagat 2580
gtcaacaata tgtgggccct cttacagtta atgaaaaaag gagattaaaa ttaattatgc 2640
ctgctaggtt ctatcctaac cttaccaaat atttgccctt ggacaaaggc attaaacctt 2700
attatcctga acatgcagtt aatcattact tcaaaactag gcattattta catactctgt 2760
ggaaggctgg cattctatat aagagagaaa ctacacgcag cgcctcattt tgtgggtcac 2820
catattcttg ggaacaagag ctacagcatg ggaggttggt cttccaaacc tcgacaaggc 2880
atggggacga atctttctgt tcccaatcct ctgggattct ttcccgatca ccagttggac 2940
cctgcgttcg gagccaactc aaacaatcca gattgggact tcaaccccaa caaggatcac 3000
tggccagagg caaatcaggt aggagcggga gcattcgggc cagggttcac cccaccacac 3060
ggcggtcttt tggggtggag ccctcaggct cagggcatat tgacaacagt gccagcagca 3120
cctcctcctg cctccaccaa tcggcagtca ggaagacagc ctactcccat ctctccacct 3180
ctaagagaca gtcatcctca ggccatgcag tggaa 3215
<210> 2
<211> 3215
<212> DNA
<213> 人工序列
<220>
<223> HBV共有序列
<400> 2
ctccacaaca ttccaccaag ctctgctaga tcccagagtg aggggcctat attttcctgc 60
tggtggctcc agttccggaa cagtaaaccc tgttccgact actgcctcac ccatatcgtc 120
aatcttctcg aggactgggg accctgcacc gaacatggag aacacaacat caggattcct 180
aggacccctg ctcgtgttac aggcggggtt tttcttgttg acaagaatcc tcacaatacc 240
acagagtcta gactcgtggt ggacttctct caattttcta gggggagcac ccacgtgtcc 300
tggccaaaat tcgcagtccc caacctccaa tcactcacca acctcttgtc ctccaatttg 360
tcctggctat cgctggatgt gtctgcggcg ttttatcata ttcctcttca tcctgctgct 420
atgcctcatc ttcttgttgg ttcttctgga ctaccaaggt atgttgcccg tttgtcctct 480
acttccagga acatcaacta ccagcacggg accatgcaag acctgcacga ttcctgctca 540
aggaacctct atgtttccct cttgttgctg tacaaaacct tcggacggaa actgcacttg 600
tattcccatc ccatcatcct gggctttcgc aagattccta tgggagtggg cctcagtccg 660
tttctcctgg ctcagtttac tagtgccatt tgttcagtgg ttcgtagggc tttcccccac 720
tgtttggctt tcagttatat ggatgatgtg gtattggggg ccaagtctgt acaacatctt 780
gagtcccttt ttacctctat taccaatttt cttttgtctt tgggtataca tttgaaccct 840
aataaaacca aacgttgggg ctactccctt aacttcatgg gatatgtaat tggaagttgg 900
ggtactttac cacaggaaca tattgtacta aaaatcaagc aatgttttcg aaaactgcct 960
gtaaatagac ctattgattg gaaagtatgt caaagaattg tgggtctttt gggctttgct 1020
gcccctttta cacaatgtgg ctatcctgcc ttgatgcctt tatatgcatg tatacaatct 1080
aagcaggctt tcactttctc gccaacttac aaggcctttc tgtgtaaaca atatctgaac 1140
ctttaccccg ttgcccggca acggtcaggt ctctgccaag tgtttgctga cgcaaccccc 1200
actggatggg gcttggccat aggccatcgg cgcatgcgtg gaacctttgt ggctcctctg 1260
ccgatccata ctgcggaact cctagcagct tgttttgctc gcagccggtc tggagcgaaa 1320
cttatcggaa ccgacaactc tgttgtcctc tctcggaaat acacctcctt tccatggctg 1380
ctagggtgtg ctgccaactg gatcctgcgc gggacgtcct ttgtctacgt cccgtcggcg 1440
ctgaatcccg cggacgaccc gtctcggggc cgtttgggac tctaccgtcc ccttcttcat 1500
ctgccgttcc ggccgaccac ggggcgcacc tctctttacg cggtctcccc gtctgtgcct 1560
tctcatctgc cggaccgtgt gcacttcgct tcacctctgc acgtcgcatg gagaccaccg 1620
tgaacgccca ccaggtcttg cccaaggtct tacataagag gactcttgga ctctcagcaa 1680
tgtcaacgac cgaccttgag gcatacttca aagactgttt gtttaaagac tgggaggagt 1740
tgggggagga gattaggtta atgatctttg tactaggagg ctgtaggcat aaattggtct 1800
gttcaccagc accatgcaac tttttcacct ctgcctaatc atctcatgtt catgtcctac 1860
tgttcaagcc tccaagctgt gccttgggtg gctttggggc atggacattg acccgtataa 1920
agaatttgga gcttctgtgg agttactctc ttttttgcct tctgacttct ttccttctat 1980
tcgagatctc ctcgacaccg cctctgctct gtatcgggag gccttagagt ctccggaaca 2040
ttgttcacct caccatacag cactcaggca agctattctg tgttggggtg agttgatgaa 2100
tctggccacc tgggtgggaa gtaatttgga agacccagca tccagggaat tagtagtcag 2160
ctatgtcaat gttaatatgg gcctaaaaat cagacaacta ttgtggtttc acatttcctg 2220
tcttactttt ggaagagaaa ctgttcttga gtatttggtg tcttttggag tgtggattcg 2280
cactcctccc gcttacagac caccaaatgc ccctatctta tcaacacttc cggaaactac 2340
tgttgttaga cgacgaggca ggtcccctag aagaagaact ccctcgcctc gcagacgaag 2400
gtctcaatcg ccgcgtcgca gaagatctca atctcgggaa tctcaatgtt agtatccctt 2460
ggactcataa ggtgggaaac tttactgggc tttattcttc tactgtacct gtctttaatc 2520
ctgagtggca aactccctcc tttcctcaca ttcatttaca ggaggacatt attaatagat 2580
gtcaacaata tgtgggccct cttacagtta atgaaaaaag gagattaaaa ttaattatgc 2640
ctgctaggtt ctatcctaac cttaccaaat atttgccctt ggacaaaggc attaaaccgt 2700
attatcctga acatgcagtt aatcattact tcaaaactag gcattattta catactctgt 2760
ggaaggctgg cattctatat aagagagaaa ctacacgcag cgcctcattt tgtgggtcac 2820
catattcttg ggaacaagag ctacagcatg ggaggttggt cttccaaacc tcgacaaggc 2880
atggggacga atctttctgt tcccaatcct ctgggattct ttcccgatca ccagttggac 2940
cctgcgttcg gagccaactc aaacaatcca gattgggact tcaaccccaa caaggatcac 3000
tggccagagg caaatcaggt aggagcggga gcattcgggc cagggttcac cccaccacac 3060
ggcggtcttt tggggtggag ccctcaggct cagggcatat tgacaacagt gccagcagca 3120
cctcctcctg cctccaccaa tcggcagtca ggaagacagc ctactcccat ctctccacct 3180
ctaagagaca gtcatcctca ggccatgcag tggaa 3215
<210> 3
<211> 1525
<212> PRT
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 3
Met Ser Leu Leu Trp Gly Gly Val Thr Val Leu Ala Ala Met Leu Ile
1 5 10 15
Ala Gly Gln Val Ala Ser Val Val Phe Leu Val Lys Gly Gly Gly Pro
20 25 30
Gly Gly Gly Met Gln Leu Phe His Leu Cys Leu Ile Ile Ser Cys Ser
35 40 45
Cys Pro Thr Val Gln Ala Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly
50 55 60
Met Asp Ile Asp Pro Tyr Lys Glu Phe Gly Ala Ser Val Glu Leu Leu
65 70 75 80
Ser Phe Leu Pro Ser Asp Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp
85 90 95
Thr Ala Ser Ala Leu Tyr Arg Glu Ala Leu Glu Ser Pro Glu His Cys
100 105 110
Ser Pro His His Thr Ala Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu
115 120 125
Leu Met Asn Leu Ala Thr Trp Val Gly Ser Asn Leu Glu Asp Pro Ala
130 135 140
Ser Arg Glu Leu Val Val Ser Tyr Val Asn Val Asn Met Gly Leu Lys
145 150 155 160
Ile Arg Gln Leu Leu Trp Phe His Ile Ser Cys Leu Thr Phe Gly Arg
165 170 175
Glu Thr Val Leu Glu Tyr Leu Val Ser Phe Gly Val Trp Ile Arg Thr
180 185 190
Pro Pro Ala Tyr Arg Pro Pro Asn Ala Pro Ile Leu Ser Thr Leu Pro
195 200 205
Glu Thr Thr Val Val Arg Arg Arg Gly Arg Ser Pro Arg Arg Arg Thr
210 215 220
Pro Ser Pro Arg Arg Arg Arg Ser Gln Ser Pro Arg Arg Arg Arg Ser
225 230 235 240
Gln Ser Arg Glu Ser Gln Cys Gly Gly Gly Ser Gly Gly Gly Met Pro
245 250 255
Leu Ser Tyr Gln His Phe Arg Lys Leu Leu Leu Leu Asp Asp Glu Ala
260 265 270
Gly Pro Leu Glu Glu Glu Leu Pro Arg Leu Ala Asp Glu Gly Leu Asn
275 280 285
Arg Arg Val Ala Glu Asp Leu Asn Leu Gly Asn Leu Asn Val Ser Ile
290 295 300
Pro Trp Thr His Lys Val Gly Asn Phe Thr Gly Leu Ala Ser Ser Thr
305 310 315 320
Val Pro Val Phe Asn Pro Glu Trp Gln Thr Pro Ser Phe Pro His Ile
325 330 335
His Leu Gln Glu Asp Ile Ile Asn Arg Cys Gln Gln Tyr Val Gly Pro
340 345 350
Leu Thr Val Asn Glu Lys Arg Arg Leu Lys Leu Ile Met Pro Ala Arg
355 360 365
Phe Tyr Pro Asn Leu Thr Lys Tyr Leu Pro Leu Asp Lys Gly Ile Lys
370 375 380
Pro Tyr Tyr Pro Glu His Ala Val Asn His Tyr Phe Lys Thr Arg His
385 390 395 400
Tyr Leu His Thr Leu Trp Lys Ala Gly Ile Leu Tyr Lys Arg Glu Thr
405 410 415
Thr Arg Ser Ala Ser Phe Cys Gly Ser Pro Tyr Ser Trp Glu Gln Glu
420 425 430
Leu Gln His Gly Arg Leu Val Phe Gln Thr Ser Thr Arg His Gly Asp
435 440 445
Glu Ser Phe Cys Ser Gln Ser Ser Gly Ile Leu Ser Arg Ser Pro Val
450 455 460
Gly Pro Cys Val Arg Ser Gln Leu Lys Gln Ser Arg Leu Gly Leu Gln
465 470 475 480
Pro Gln Gln Gly Ser Leu Ala Arg Gly Lys Ser Gly Arg Ser Gly Ser
485 490 495
Ile Arg Ala Arg Val His Pro Thr Thr Arg Arg Ser Phe Gly Val Glu
500 505 510
Pro Ser Gly Ser Gly His Ile Asp Asn Ser Ala Ser Ser Thr Ser Ser
515 520 525
Cys Leu His Gln Ser Ala Val Arg Lys Thr Ala Tyr Ser His Leu Ser
530 535 540
Thr Ser Lys Arg Gln Ser Ser Ser Gly His Ala Val Glu Leu His Asn
545 550 555 560
Ile Pro Pro Ser Ser Ala Arg Ser Gln Ser Glu Gly Pro Ile Phe Ser
565 570 575
Ala Trp Trp Leu Gln Phe Arg Asn Ser Lys Pro Ala Ser Asp Tyr Ala
580 585 590
Leu Thr His Ile Val Asn Leu Leu Glu Asp Trp Gly Pro Ala Thr Glu
595 600 605
His Gly Glu His Asn Ile Arg Ile Pro Arg Thr Pro Ala Arg Val Thr
610 615 620
Gly Gly Val Phe Leu Val Asp Lys Asn Pro His Asn Thr Thr Glu Ser
625 630 635 640
Arg Leu Val Val Asp Phe Ser Gln Phe Ser Arg Gly Ser Thr His Val
645 650 655
Ser Trp Pro Lys Phe Ala Val Pro Asn Leu Gln Ser Leu Thr Asn Leu
660 665 670
Leu Ser Ser Asn Leu Ser Trp Leu Ser Leu Asp Val Ser Ala Ala Phe
675 680 685
Tyr His Ile Pro Leu His Pro Ala Ala Met Pro His Leu Leu Val Gly
690 695 700
Ser Ser Gly Leu Pro Arg Tyr Val Ala Arg Leu Ser Ser Thr Ser Arg
705 710 715 720
Asn Ile Asn Tyr Gln His Gly Thr Met Gln Asp Leu His Asp Ser Cys
725 730 735
Ser Arg Asn Leu Tyr Val Ser Leu Leu Leu Leu Tyr Lys Thr Phe Gly
740 745 750
Arg Lys Leu His Leu Tyr Ser His Pro Ile Ile Leu Gly Phe Arg Lys
755 760 765
Ile Pro Met Gly Val Gly Leu Ser Pro Phe Leu Leu Ala Gln Phe Thr
770 775 780
Ser Ala Ile Cys Ser Val Val Arg Arg Ala Phe Pro His Cys Leu Ala
785 790 795 800
Phe Ser Tyr Met Asp Asp Val Val Leu Gly Ala Lys Ser Val Gln His
805 810 815
Leu Glu Ser Leu Phe Thr Ser Ile Thr Asn Phe Leu Leu Ser Leu Gly
820 825 830
Ile His Leu Asn Pro Asn Lys Thr Lys Arg Trp Gly Tyr Ser Leu Asn
835 840 845
Phe Met Gly Tyr Val Ile Gly Ser Trp Gly Thr Leu Pro Gln Glu His
850 855 860
Ile Val Leu Lys Ile Lys Gln Cys Phe Arg Lys Leu Pro Val Asn Arg
865 870 875 880
Pro Ile Asp Trp Lys Val Cys Gln Arg Ile Val Gly Leu Leu Gly Phe
885 890 895
Ala Ala Pro Phe Thr Gln Cys Gly Tyr Pro Ala Leu Met Pro Leu Tyr
900 905 910
Ala Cys Ile Gln Ser Lys Gln Ala Phe Thr Phe Ser Pro Thr Tyr Lys
915 920 925
Ala Phe Leu Cys Lys Gln Tyr Leu Asn Leu Tyr Pro Val Ala Arg Gln
930 935 940
Arg Ser Gly Leu Cys Gln Val Phe Ala Asp Ala Thr Pro Thr Gly Trp
945 950 955 960
Gly Leu Ala Ile Gly His Arg Ala Met Arg Gly Thr Phe Val Ala Pro
965 970 975
Leu Pro Ile His Thr Ala Glu Leu Leu Ala Ala Cys Phe Ala Arg Ser
980 985 990
Arg Ser Gly Ala Lys Leu Ile Gly Thr Asp Asn Ser Val Val Leu Ser
995 1000 1005
Arg Lys Tyr Thr Ser Phe Pro Trp Leu Leu Gly Cys Ala Ala Asn
1010 1015 1020
Trp Ile Leu Arg Gly Thr Ser Phe Val Tyr Val Pro Ser Ala Leu
1025 1030 1035
Asn Pro Ala Ala Asp Pro Ser Ala Gly Arg Leu Gly Leu Tyr Arg
1040 1045 1050
Pro Leu Leu His Leu Pro Phe Arg Pro Thr Thr Gly Arg Thr Ser
1055 1060 1065
Leu Tyr Ala Val Ser Pro Ser Val Pro Ser His Leu Pro Asp Arg
1070 1075 1080
Val His Phe Ala Ser Pro Leu His Val Ala Trp Arg Pro Pro Arg
1085 1090 1095
Lys Arg Arg Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu
1100 1105 1110
Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Met Gly Gly
1115 1120 1125
Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn Leu Ser Val
1130 1135 1140
Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu Asp Pro Ala
1145 1150 1155
Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro Asn
1160 1165 1170
Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala Gly Ala Phe
1175 1180 1185
Gly Pro Gly Phe Thr Pro Pro His Gly Gly Leu Leu Gly Trp Ser
1190 1195 1200
Pro Gln Ala Gln Gly Ile Leu Thr Thr Val Pro Ala Ala Pro Pro
1205 1210 1215
Pro Ala Ser Thr Asn Arg Gln Ser Gly Arg Gln Pro Thr Pro Ile
1220 1225 1230
Ser Pro Pro Leu Arg Asp Ser His Pro Gln Ala Met Gln Trp Asn
1235 1240 1245
Ser Thr Thr Phe His Gln Ala Leu Leu Asp Pro Arg Val Arg Gly
1250 1255 1260
Leu Tyr Phe Pro Ala Gly Gly Ser Ser Ser Gly Thr Val Asn Pro
1265 1270 1275
Val Pro Thr Thr Ala Ser Pro Ile Ser Ser Ile Phe Ser Arg Thr
1280 1285 1290
Gly Asp Pro Ala Pro Asn Met Glu Asn Thr Thr Ser Gly Phe Leu
1295 1300 1305
Gly Pro Leu Leu Val Leu Gln Ala Gly Phe Phe Leu Leu Thr Arg
1310 1315 1320
Ile Leu Thr Ile Pro Gln Ser Leu Asp Ser Trp Trp Thr Ser Leu
1325 1330 1335
Asn Phe Leu Gly Gly Ala Pro Thr Cys Pro Gly Gln Asn Ser Gln
1340 1345 1350
Ser Pro Thr Ser Asn His Ser Pro Thr Ser Cys Pro Pro Ile Cys
1355 1360 1365
Pro Gly Tyr Arg Trp Met Cys Leu Arg Arg Phe Ile Ile Phe Leu
1370 1375 1380
Phe Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu Val Leu Leu Asp
1385 1390 1395
Tyr Gln Gly Met Leu Pro Val Cys Pro Leu Leu Pro Gly Thr Ser
1400 1405 1410
Thr Thr Ser Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala Gln
1415 1420 1425
Gly Thr Ser Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp
1430 1435 1440
Gly Asn Cys Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala
1445 1450 1455
Arg Phe Leu Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser
1460 1465 1470
Leu Leu Val Pro Phe Val Gln Trp Phe Val Gly Leu Ser Pro Thr
1475 1480 1485
Val Trp Leu Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro Ser
1490 1495 1500
Leu Tyr Asn Ile Leu Ser Pro Phe Leu Pro Leu Leu Pro Ile Phe
1505 1510 1515
Phe Cys Leu Trp Val Tyr Ile
1520 1525
<210> 4
<211> 26
<212> PRT
<213> 未知
<220>
<223> 鲨鱼恒定链
<400> 4
Ser Leu Leu Trp Gly Gly Val Thr Val Leu Ala Ala Met Leu Ile Ala
1 5 10 15
Gly Gln Val Ala Ser Val Val Phe Leu Val
20 25
<210> 5
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 5
Lys Gly Gly Gly Pro Gly Gly Gly
1 5
<210> 6
<211> 183
<212> PRT
<213> 乙型肝炎病毒
<400> 6
Met Asp Ile Asp Pro Tyr Lys Glu Phe Gly Ala Ser Val Glu Leu Leu
1 5 10 15
Ser Phe Leu Pro Ser Asp Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp
20 25 30
Thr Ala Ser Ala Leu Tyr Arg Glu Ala Leu Glu Ser Pro Glu His Cys
35 40 45
Ser Pro His His Thr Ala Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu
50 55 60
Leu Met Asn Leu Ala Thr Trp Val Gly Ser Asn Leu Glu Asp Pro Ala
65 70 75 80
Ser Arg Glu Leu Val Val Ser Tyr Val Asn Val Asn Met Gly Leu Lys
85 90 95
Ile Arg Gln Leu Leu Trp Phe His Ile Ser Cys Leu Thr Phe Gly Arg
100 105 110
Glu Thr Val Leu Glu Tyr Leu Val Ser Phe Gly Val Trp Ile Arg Thr
115 120 125
Pro Pro Ala Tyr Arg Pro Pro Asn Ala Pro Ile Leu Ser Thr Leu Pro
130 135 140
Glu Thr Thr Val Val Arg Arg Arg Gly Arg Ser Pro Arg Arg Arg Thr
145 150 155 160
Pro Ser Pro Arg Arg Arg Arg Ser Gln Ser Pro Arg Arg Arg Arg Ser
165 170 175
Gln Ser Arg Glu Ser Gln Cys
180
<210> 7
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 7
Gly Gly Gly Ser Gly Gly Gly
1 5
<210> 8
<211> 772
<212> PRT
<213> 乙型肝炎病毒
<400> 8
Met Pro Leu Ser Tyr Gln His Phe Arg Lys Leu Leu Leu Leu Asp Asp
1 5 10 15
Glu Ala Gly Pro Leu Glu Glu Glu Leu Pro Arg Leu Ala Asp Glu Gly
20 25 30
Leu Asn Arg Arg Val Ala Glu Asp Leu Asn Leu Gly Asn Leu Asn Val
35 40 45
Ser Ile Pro Trp Thr His Lys Val Gly Asn Phe Thr Gly Leu Ala Ser
50 55 60
Ser Thr Val Pro Val Phe Asn Pro Glu Trp Gln Thr Pro Ser Phe Pro
65 70 75 80
His Ile His Leu Gln Glu Asp Ile Ile Asn Arg Cys Gln Gln Tyr Val
85 90 95
Gly Pro Leu Thr Val Asn Glu Lys Arg Arg Leu Lys Leu Ile Met Pro
100 105 110
Ala Arg Phe Tyr Pro Asn Leu Thr Lys Tyr Leu Pro Leu Asp Lys Gly
115 120 125
Ile Lys Pro Tyr Tyr Pro Glu His Ala Val Asn His Tyr Phe Lys Thr
130 135 140
Arg His Tyr Leu His Thr Leu Trp Lys Ala Gly Ile Leu Tyr Lys Arg
145 150 155 160
Glu Thr Thr Arg Ser Ala Ser Phe Cys Gly Ser Pro Tyr Ser Trp Glu
165 170 175
Gln Glu Leu Gln His Gly Arg Leu Val Phe Gln Thr Ser Thr Arg His
180 185 190
Gly Asp Glu Ser Phe Cys Ser Gln Ser Ser Gly Ile Leu Ser Arg Ser
195 200 205
Pro Val Gly Pro Cys Val Arg Ser Gln Leu Lys Gln Ser Arg Leu Gly
210 215 220
Leu Gln Pro Gln Gln Gly Ser Leu Ala Arg Gly Lys Ser Gly Arg Ser
225 230 235 240
Gly Ser Ile Arg Ala Arg Val His Pro Thr Thr Arg Arg Ser Phe Gly
245 250 255
Val Glu Pro Ser Gly Ser Gly His Ile Asp Asn Ser Ala Ser Ser Thr
260 265 270
Ser Ser Cys Leu His Gln Ser Ala Val Arg Lys Thr Ala Tyr Ser His
275 280 285
Leu Ser Thr Ser Lys Arg Gln Ser Ser Ser Gly His Ala Val Glu Leu
290 295 300
His Asn Ile Pro Pro Ser Ser Ala Arg Ser Gln Ser Glu Gly Pro Ile
305 310 315 320
Phe Ser Ala Trp Trp Leu Gln Phe Arg Asn Ser Lys Pro Ala Ser Asp
325 330 335
Tyr Ala Leu Thr His Ile Val Asn Leu Leu Glu Asp Trp Gly Pro Ala
340 345 350
Thr Glu His Gly Glu His Asn Ile Arg Ile Pro Arg Thr Pro Ala Arg
355 360 365
Val Thr Gly Gly Val Phe Leu Val Asp Lys Asn Pro His Asn Thr Thr
370 375 380
Glu Ser Arg Leu Val Val Asp Phe Ser Gln Phe Ser Arg Gly Ser Thr
385 390 395 400
His Val Ser Trp Pro Lys Phe Ala Val Pro Asn Leu Gln Ser Leu Thr
405 410 415
Asn Leu Leu Ser Ser Asn Leu Ser Thr Phe Gly Arg Lys Leu His Leu
420 425 430
Tyr Ser His Pro Ile Ile Leu Gly Phe Arg Lys Ile Pro Met Gly Val
435 440 445
Gly Leu Ser Pro Phe Leu Leu Ala Gln Phe Thr Ser Ala Ile Cys Ser
450 455 460
Val Val Arg Arg Ala Phe Pro His Cys Leu Ala Phe Ser Tyr Met Asp
465 470 475 480
Asp Val Val Leu Gly Ala Lys Ser Val Gln His Leu Glu Ser Leu Phe
485 490 495
Thr Ser Ile Thr Asn Phe Leu Leu Ser Leu Gly Ile His Leu Asn Pro
500 505 510
Asn Lys Thr Lys Arg Trp Gly Tyr Ser Leu Asn Phe Met Gly Tyr Val
515 520 525
Ile Gly Ser Trp Gly Thr Leu Pro Gln Glu His Ile Val Leu Lys Ile
530 535 540
Lys Gln Cys Phe Arg Lys Leu Pro Val Asn Arg Pro Ile Asp Trp Lys
545 550 555 560
Val Cys Gln Arg Ile Val Gly Leu Leu Gly Phe Ala Ala Pro Phe Thr
565 570 575
Gln Cys Gly Tyr Pro Ala Leu Met Pro Leu Tyr Ala Cys Ile Gln Ser
580 585 590
Lys Gln Ala Phe Thr Phe Ser Pro Thr Tyr Lys Ala Phe Leu Cys Lys
595 600 605
Gln Tyr Leu Asn Leu Tyr Pro Val Ala Arg Gln Arg Ser Gly Leu Cys
610 615 620
Gln Val Phe Ala Asp Ala Thr Pro Thr Gly Trp Gly Leu Ala Ile Gly
625 630 635 640
His Arg Ala Met Arg Gly Thr Phe Val Ala Pro Leu Pro Ile His Thr
645 650 655
Ala Glu Leu Leu Ala Ala Cys Phe Ala Arg Ser Arg Ser Gly Ala Lys
660 665 670
Leu Ile Gly Thr Asp Asn Ser Val Val Leu Ser Arg Lys Tyr Thr Ser
675 680 685
Phe Pro Trp Leu Leu Gly Cys Ala Ala Asn Trp Ile Leu Arg Gly Thr
690 695 700
Ser Phe Val Tyr Val Pro Ser Ala Leu Asn Pro Ala Ala Asp Pro Ser
705 710 715 720
Ala Gly Arg Leu Gly Leu Tyr Arg Pro Leu Leu His Leu Pro Phe Arg
725 730 735
Pro Thr Thr Gly Arg Thr Ser Leu Tyr Ala Val Ser Pro Ser Val Pro
740 745 750
Ser His Leu Pro Asp Arg Val His Phe Ala Ser Pro Leu His Val Ala
755 760 765
Trp Arg Pro Pro
770
<210> 9
<211> 28
<212> PRT
<213> 未知
<220>
<223> 弗林蛋白酶2A
<400> 9
Arg Lys Arg Arg Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu
1 5 10 15
Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro
20 25
<210> 10
<211> 226
<212> PRT
<213> 乙型肝炎病毒
<400> 10
Met Glu Asn Thr Thr Ser Gly Phe Leu Gly Pro Leu Leu Val Leu Gln
1 5 10 15
Ala Gly Phe Phe Leu Leu Thr Arg Ile Leu Thr Ile Pro Gln Ser Leu
20 25 30
Asp Ser Trp Trp Thr Ser Leu Asn Phe Leu Gly Gly Ala Pro Thr Cys
35 40 45
Pro Gly Gln Asn Ser Gln Ser Pro Thr Ser Asn His Ser Pro Thr Ser
50 55 60
Cys Pro Pro Ile Cys Pro Gly Tyr Arg Trp Met Cys Leu Arg Arg Phe
65 70 75 80
Ile Ile Phe Leu Phe Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu Val
85 90 95
Leu Leu Asp Tyr Gln Gly Met Leu Pro Val Cys Pro Leu Leu Pro Gly
100 105 110
Thr Ser Thr Thr Ser Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala
115 120 125
Gln Gly Thr Ser Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp
130 135 140
Gly Asn Cys Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala Arg
145 150 155 160
Phe Leu Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu Leu
165 170 175
Val Pro Phe Val Gln Trp Phe Val Gly Leu Ser Pro Thr Val Trp Leu
180 185 190
Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro Ser Leu Tyr Asn Ile
195 200 205
Leu Ser Pro Phe Leu Pro Leu Leu Pro Ile Phe Phe Cys Leu Trp Val
210 215 220
Tyr Ile
225
<210> 11
<211> 1521
<212> PRT
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 11
Met Ser Leu Leu Trp Gly Gly Val Thr Val Leu Ala Ala Met Leu Ile
1 5 10 15
Ala Gly Gln Val Ala Ser Val Val Phe Leu Val Lys Gly Gly Ser Met
20 25 30
Gly Gly Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn Leu Ser
35 40 45
Val Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu Asp Pro Ala
50 55 60
Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro Asn Lys
65 70 75 80
Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala Gly Ala Phe Gly Pro
85 90 95
Gly Phe Thr Pro Pro His Gly Gly Leu Leu Gly Trp Ser Pro Gln Ala
100 105 110
Gln Gly Ile Leu Thr Thr Val Pro Ala Ala Pro Pro Pro Ala Ser Thr
115 120 125
Asn Arg Gln Ser Gly Arg Gln Pro Thr Pro Ile Ser Pro Pro Leu Arg
130 135 140
Asp Ser His Pro Gln Ala Met Gln Trp Asn Ser Thr Thr Phe His Gln
145 150 155 160
Ala Leu Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly
165 170 175
Ser Ser Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser Pro Ile
180 185 190
Ser Ser Ile Phe Ser Arg Thr Gly Asp Pro Ala Pro Asn Met Glu Asn
195 200 205
Thr Thr Ser Gly Phe Leu Gly Pro Leu Leu Val Leu Gln Ala Gly Phe
210 215 220
Phe Leu Leu Thr Arg Ile Leu Thr Ile Pro Gln Ser Leu Asp Ser Trp
225 230 235 240
Trp Thr Ser Leu Asn Phe Leu Gly Gly Ala Pro Thr Cys Pro Gly Gln
245 250 255
Asn Ser Gln Ser Pro Thr Ser Asn His Ser Pro Thr Ser Cys Pro Pro
260 265 270
Ile Cys Pro Gly Tyr Arg Trp Met Cys Leu Arg Arg Phe Ile Ile Phe
275 280 285
Leu Phe Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu Val Leu Leu Asp
290 295 300
Tyr Gln Gly Met Leu Pro Val Cys Pro Leu Leu Pro Gly Thr Ser Thr
305 310 315 320
Thr Ser Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala Gln Gly Thr
325 330 335
Ser Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp Gly Asn Cys
340 345 350
Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala Arg Phe Leu Trp
355 360 365
Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu Leu Val Pro Phe
370 375 380
Val Gln Trp Phe Val Gly Leu Ser Pro Thr Val Trp Leu Ser Val Ile
385 390 395 400
Trp Met Met Trp Tyr Trp Gly Pro Ser Leu Tyr Asn Ile Leu Ser Pro
405 410 415
Phe Leu Pro Leu Leu Pro Ile Phe Phe Cys Leu Trp Val Tyr Ile Arg
420 425 430
Lys Arg Arg Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys
435 440 445
Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Met Gln Leu Phe His
450 455 460
Leu Cys Leu Ile Ile Ser Cys Ser Cys Pro Thr Val Gln Ala Ser Lys
465 470 475 480
Leu Cys Leu Gly Trp Leu Trp Gly Met Asp Ile Asp Pro Tyr Lys Glu
485 490 495
Phe Gly Ala Ser Val Glu Leu Leu Ser Phe Leu Pro Ser Asp Phe Phe
500 505 510
Pro Ser Ile Arg Asp Leu Leu Asp Thr Ala Ser Ala Leu Tyr Arg Glu
515 520 525
Ala Leu Glu Ser Pro Glu His Cys Ser Pro His His Thr Ala Leu Arg
530 535 540
Gln Ala Ile Leu Cys Trp Gly Glu Leu Met Asn Leu Ala Thr Trp Val
545 550 555 560
Gly Ser Asn Leu Glu Asp Pro Ala Ser Arg Glu Leu Val Val Ser Tyr
565 570 575
Val Asn Val Asn Met Gly Leu Lys Ile Arg Gln Leu Leu Trp Phe His
580 585 590
Ile Ser Cys Leu Thr Phe Gly Arg Glu Thr Val Leu Glu Tyr Leu Val
595 600 605
Ser Phe Gly Val Trp Ile Arg Thr Pro Pro Ala Tyr Arg Pro Pro Asn
610 615 620
Ala Pro Ile Leu Ser Thr Leu Pro Glu Thr Thr Val Val Arg Arg Arg
625 630 635 640
Gly Arg Ser Pro Arg Arg Arg Thr Pro Ser Pro Arg Arg Arg Arg Ser
645 650 655
Gln Ser Pro Arg Arg Arg Arg Ser Gln Ser Arg Glu Ser Gln Cys Gly
660 665 670
Gly Gly Ser Gly Gly Gly Met Pro Leu Ser Tyr Gln His Phe Arg Lys
675 680 685
Leu Leu Leu Leu Asp Asp Glu Ala Gly Pro Leu Glu Glu Glu Leu Pro
690 695 700
Arg Leu Ala Asp Glu Gly Leu Asn Arg Arg Val Ala Glu Asp Leu Asn
705 710 715 720
Leu Gly Asn Leu Asn Val Ser Ile Pro Trp Thr His Lys Val Gly Asn
725 730 735
Phe Thr Gly Leu Ala Ser Ser Thr Val Pro Val Phe Asn Pro Glu Trp
740 745 750
Gln Thr Pro Ser Phe Pro His Ile His Leu Gln Glu Asp Ile Ile Asn
755 760 765
Arg Cys Gln Gln Tyr Val Gly Pro Leu Thr Val Asn Glu Lys Arg Arg
770 775 780
Leu Lys Leu Ile Met Pro Ala Arg Phe Tyr Pro Asn Leu Thr Lys Tyr
785 790 795 800
Leu Pro Leu Asp Lys Gly Ile Lys Pro Tyr Tyr Pro Glu His Ala Val
805 810 815
Asn His Tyr Phe Lys Thr Arg His Tyr Leu His Thr Leu Trp Lys Ala
820 825 830
Gly Ile Leu Tyr Lys Arg Glu Thr Thr Arg Ser Ala Ser Phe Cys Gly
835 840 845
Ser Pro Tyr Ser Trp Glu Gln Glu Leu Gln His Gly Arg Leu Val Phe
850 855 860
Gln Thr Ser Thr Arg His Gly Asp Glu Ser Phe Cys Ser Gln Ser Ser
865 870 875 880
Gly Ile Leu Ser Arg Ser Pro Val Gly Pro Cys Val Arg Ser Gln Leu
885 890 895
Lys Gln Ser Arg Leu Gly Leu Gln Pro Gln Gln Gly Ser Leu Ala Arg
900 905 910
Gly Lys Ser Gly Arg Ser Gly Ser Ile Arg Ala Arg Val His Pro Thr
915 920 925
Thr Arg Arg Ser Phe Gly Val Glu Pro Ser Gly Ser Gly His Ile Asp
930 935 940
Asn Ser Ala Ser Ser Thr Ser Ser Cys Leu His Gln Ser Ala Val Arg
945 950 955 960
Lys Thr Ala Tyr Ser His Leu Ser Thr Ser Lys Arg Gln Ser Ser Ser
965 970 975
Gly His Ala Val Glu Leu His Asn Ile Pro Pro Ser Ser Ala Arg Ser
980 985 990
Gln Ser Glu Gly Pro Ile Phe Ser Ala Trp Trp Leu Gln Phe Arg Asn
995 1000 1005
Ser Lys Pro Ala Ser Asp Tyr Ala Leu Thr His Ile Val Asn Leu
1010 1015 1020
Leu Glu Asp Trp Gly Pro Ala Thr Glu His Gly Glu His Asn Ile
1025 1030 1035
Arg Ile Pro Arg Thr Pro Ala Arg Val Thr Gly Gly Val Phe Leu
1040 1045 1050
Val Asp Lys Asn Pro His Asn Thr Thr Glu Ser Arg Leu Val Val
1055 1060 1065
Asp Phe Ser Gln Phe Ser Arg Gly Ser Thr His Val Ser Trp Pro
1070 1075 1080
Lys Phe Ala Val Pro Asn Leu Gln Ser Leu Thr Asn Leu Leu Ser
1085 1090 1095
Ser Asn Leu Ser Trp Leu Ser Leu Asp Val Ser Ala Ala Phe Tyr
1100 1105 1110
His Ile Pro Leu His Pro Ala Ala Met Pro His Leu Leu Val Gly
1115 1120 1125
Ser Ser Gly Leu Pro Arg Tyr Val Ala Arg Leu Ser Ser Thr Ser
1130 1135 1140
Arg Asn Ile Asn Tyr Gln His Gly Thr Met Gln Asp Leu His Asp
1145 1150 1155
Ser Cys Ser Arg Asn Leu Tyr Val Ser Leu Leu Leu Leu Tyr Lys
1160 1165 1170
Thr Phe Gly Arg Lys Leu His Leu Tyr Ser His Pro Ile Ile Leu
1175 1180 1185
Gly Phe Arg Lys Ile Pro Met Gly Val Gly Leu Ser Pro Phe Leu
1190 1195 1200
Leu Ala Gln Phe Thr Ser Ala Ile Cys Ser Val Val Arg Arg Ala
1205 1210 1215
Phe Pro His Cys Leu Ala Phe Ser Tyr Met Asp Asp Val Val Leu
1220 1225 1230
Gly Ala Lys Ser Val Gln His Leu Glu Ser Leu Phe Thr Ser Ile
1235 1240 1245
Thr Asn Phe Leu Leu Ser Leu Gly Ile His Leu Asn Pro Asn Lys
1250 1255 1260
Thr Lys Arg Trp Gly Tyr Ser Leu Asn Phe Met Gly Tyr Val Ile
1265 1270 1275
Gly Ser Trp Gly Thr Leu Pro Gln Glu His Ile Val Leu Lys Ile
1280 1285 1290
Lys Gln Cys Phe Arg Lys Leu Pro Val Asn Arg Pro Ile Asp Trp
1295 1300 1305
Lys Val Cys Gln Arg Ile Val Gly Leu Leu Gly Phe Ala Ala Pro
1310 1315 1320
Phe Thr Gln Cys Gly Tyr Pro Ala Leu Met Pro Leu Tyr Ala Cys
1325 1330 1335
Ile Gln Ser Lys Gln Ala Phe Thr Phe Ser Pro Thr Tyr Lys Ala
1340 1345 1350
Phe Leu Cys Lys Gln Tyr Leu Asn Leu Tyr Pro Val Ala Arg Gln
1355 1360 1365
Arg Ser Gly Leu Cys Gln Val Phe Ala Asp Ala Thr Pro Thr Gly
1370 1375 1380
Trp Gly Leu Ala Ile Gly His Arg Ala Met Arg Gly Thr Phe Val
1385 1390 1395
Ala Pro Leu Pro Ile His Thr Ala Glu Leu Leu Ala Ala Cys Phe
1400 1405 1410
Ala Arg Ser Arg Ser Gly Ala Lys Leu Ile Gly Thr Asp Asn Ser
1415 1420 1425
Val Val Leu Ser Arg Lys Tyr Thr Ser Phe Pro Trp Leu Leu Gly
1430 1435 1440
Cys Ala Ala Asn Trp Ile Leu Arg Gly Thr Ser Phe Val Tyr Val
1445 1450 1455
Pro Ser Ala Leu Asn Pro Ala Ala Asp Pro Ser Ala Gly Arg Leu
1460 1465 1470
Gly Leu Tyr Arg Pro Leu Leu His Leu Pro Phe Arg Pro Thr Thr
1475 1480 1485
Gly Arg Thr Ser Leu Tyr Ala Val Ser Pro Ser Val Pro Ser His
1490 1495 1500
Leu Pro Asp Arg Val His Phe Ala Ser Pro Leu His Val Ala Trp
1505 1510 1515
Arg Pro Pro
1520
<210> 12
<211> 1490
<212> PRT
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 12
Met Gln Leu Phe His Leu Cys Leu Ile Ile Ser Cys Ser Cys Pro Thr
1 5 10 15
Val Gln Ala Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly Met Asp Ile
20 25 30
Asp Pro Tyr Lys Glu Phe Gly Ala Ser Val Glu Leu Leu Ser Phe Leu
35 40 45
Pro Ser Asp Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp Thr Ala Ser
50 55 60
Ala Leu Tyr Arg Glu Ala Leu Glu Ser Pro Glu His Cys Ser Pro His
65 70 75 80
His Thr Ala Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu Leu Met Asn
85 90 95
Leu Ala Thr Trp Val Gly Ser Asn Leu Glu Asp Pro Ala Ser Arg Glu
100 105 110
Leu Val Val Ser Tyr Val Asn Val Asn Met Gly Leu Lys Ile Arg Gln
115 120 125
Leu Leu Trp Phe His Ile Ser Cys Leu Thr Phe Gly Arg Glu Thr Val
130 135 140
Leu Glu Tyr Leu Val Ser Phe Gly Val Trp Ile Arg Thr Pro Pro Ala
145 150 155 160
Tyr Arg Pro Pro Asn Ala Pro Ile Leu Ser Thr Leu Pro Glu Thr Thr
165 170 175
Val Val Arg Arg Arg Gly Arg Ser Pro Arg Arg Arg Thr Pro Ser Pro
180 185 190
Arg Arg Arg Arg Ser Gln Ser Pro Arg Arg Arg Arg Ser Gln Ser Arg
195 200 205
Glu Ser Gln Cys Gly Gly Gly Ser Gly Gly Gly Met Pro Leu Ser Tyr
210 215 220
Gln His Phe Arg Lys Leu Leu Leu Leu Asp Asp Glu Ala Gly Pro Leu
225 230 235 240
Glu Glu Glu Leu Pro Arg Leu Ala Asp Glu Gly Leu Asn Arg Arg Val
245 250 255
Ala Glu Asp Leu Asn Leu Gly Asn Leu Asn Val Ser Ile Pro Trp Thr
260 265 270
His Lys Val Gly Asn Phe Thr Gly Leu Ala Ser Ser Thr Val Pro Val
275 280 285
Phe Asn Pro Glu Trp Gln Thr Pro Ser Phe Pro His Ile His Leu Gln
290 295 300
Glu Asp Ile Ile Asn Arg Cys Gln Gln Tyr Val Gly Pro Leu Thr Val
305 310 315 320
Asn Glu Lys Arg Arg Leu Lys Leu Ile Met Pro Ala Arg Phe Tyr Pro
325 330 335
Asn Leu Thr Lys Tyr Leu Pro Leu Asp Lys Gly Ile Lys Pro Tyr Tyr
340 345 350
Pro Glu His Ala Val Asn His Tyr Phe Lys Thr Arg His Tyr Leu His
355 360 365
Thr Leu Trp Lys Ala Gly Ile Leu Tyr Lys Arg Glu Thr Thr Arg Ser
370 375 380
Ala Ser Phe Cys Gly Ser Pro Tyr Ser Trp Glu Gln Glu Leu Gln His
385 390 395 400
Gly Arg Leu Val Phe Gln Thr Ser Thr Arg His Gly Asp Glu Ser Phe
405 410 415
Cys Ser Gln Ser Ser Gly Ile Leu Ser Arg Ser Pro Val Gly Pro Cys
420 425 430
Val Arg Ser Gln Leu Lys Gln Ser Arg Leu Gly Leu Gln Pro Gln Gln
435 440 445
Gly Ser Leu Ala Arg Gly Lys Ser Gly Arg Ser Gly Ser Ile Arg Ala
450 455 460
Arg Val His Pro Thr Thr Arg Arg Ser Phe Gly Val Glu Pro Ser Gly
465 470 475 480
Ser Gly His Ile Asp Asn Ser Ala Ser Ser Thr Ser Ser Cys Leu His
485 490 495
Gln Ser Ala Val Arg Lys Thr Ala Tyr Ser His Leu Ser Thr Ser Lys
500 505 510
Arg Gln Ser Ser Ser Gly His Ala Val Glu Leu His Asn Ile Pro Pro
515 520 525
Ser Ser Ala Arg Ser Gln Ser Glu Gly Pro Ile Phe Ser Ala Trp Trp
530 535 540
Leu Gln Phe Arg Asn Ser Lys Pro Ala Ser Asp Tyr Ala Leu Thr His
545 550 555 560
Ile Val Asn Leu Leu Glu Asp Trp Gly Pro Ala Thr Glu His Gly Glu
565 570 575
His Asn Ile Arg Ile Pro Arg Thr Pro Ala Arg Val Thr Gly Gly Val
580 585 590
Phe Leu Val Asp Lys Asn Pro His Asn Thr Thr Glu Ser Arg Leu Val
595 600 605
Val Asp Phe Ser Gln Phe Ser Arg Gly Ser Thr His Val Ser Trp Pro
610 615 620
Lys Phe Ala Val Pro Asn Leu Gln Ser Leu Thr Asn Leu Leu Ser Ser
625 630 635 640
Asn Leu Ser Trp Leu Ser Leu Asp Val Ser Ala Ala Phe Tyr His Ile
645 650 655
Pro Leu His Pro Ala Ala Met Pro His Leu Leu Val Gly Ser Ser Gly
660 665 670
Leu Pro Arg Tyr Val Ala Arg Leu Ser Ser Thr Ser Arg Asn Ile Asn
675 680 685
Tyr Gln His Gly Thr Met Gln Asp Leu His Asp Ser Cys Ser Arg Asn
690 695 700
Leu Tyr Val Ser Leu Leu Leu Leu Tyr Lys Thr Phe Gly Arg Lys Leu
705 710 715 720
His Leu Tyr Ser His Pro Ile Ile Leu Gly Phe Arg Lys Ile Pro Met
725 730 735
Gly Val Gly Leu Ser Pro Phe Leu Leu Ala Gln Phe Thr Ser Ala Ile
740 745 750
Cys Ser Val Val Arg Arg Ala Phe Pro His Cys Leu Ala Phe Ser Tyr
755 760 765
Met Asp Asp Val Val Leu Gly Ala Lys Ser Val Gln His Leu Glu Ser
770 775 780
Leu Phe Thr Ser Ile Thr Asn Phe Leu Leu Ser Leu Gly Ile His Leu
785 790 795 800
Asn Pro Asn Lys Thr Lys Arg Trp Gly Tyr Ser Leu Asn Phe Met Gly
805 810 815
Tyr Val Ile Gly Ser Trp Gly Thr Leu Pro Gln Glu His Ile Val Leu
820 825 830
Lys Ile Lys Gln Cys Phe Arg Lys Leu Pro Val Asn Arg Pro Ile Asp
835 840 845
Trp Lys Val Cys Gln Arg Ile Val Gly Leu Leu Gly Phe Ala Ala Pro
850 855 860
Phe Thr Gln Cys Gly Tyr Pro Ala Leu Met Pro Leu Tyr Ala Cys Ile
865 870 875 880
Gln Ser Lys Gln Ala Phe Thr Phe Ser Pro Thr Tyr Lys Ala Phe Leu
885 890 895
Cys Lys Gln Tyr Leu Asn Leu Tyr Pro Val Ala Arg Gln Arg Ser Gly
900 905 910
Leu Cys Gln Val Phe Ala Asp Ala Thr Pro Thr Gly Trp Gly Leu Ala
915 920 925
Ile Gly His Arg Ala Met Arg Gly Thr Phe Val Ala Pro Leu Pro Ile
930 935 940
His Thr Ala Glu Leu Leu Ala Ala Cys Phe Ala Arg Ser Arg Ser Gly
945 950 955 960
Ala Lys Leu Ile Gly Thr Asp Asn Ser Val Val Leu Ser Arg Lys Tyr
965 970 975
Thr Ser Phe Pro Trp Leu Leu Gly Cys Ala Ala Asn Trp Ile Leu Arg
980 985 990
Gly Thr Ser Phe Val Tyr Val Pro Ser Ala Leu Asn Pro Ala Ala Asp
995 1000 1005
Pro Ser Ala Gly Arg Leu Gly Leu Tyr Arg Pro Leu Leu His Leu
1010 1015 1020
Pro Phe Arg Pro Thr Thr Gly Arg Thr Ser Leu Tyr Ala Val Ser
1025 1030 1035
Pro Ser Val Pro Ser His Leu Pro Asp Arg Val His Phe Ala Ser
1040 1045 1050
Pro Leu His Val Ala Trp Arg Pro Pro Arg Lys Arg Arg Ala Pro
1055 1060 1065
Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp
1070 1075 1080
Val Glu Ser Asn Pro Gly Pro Met Gly Gly Trp Ser Ser Lys Pro
1085 1090 1095
Arg Gln Gly Met Gly Thr Asn Leu Ser Val Pro Asn Pro Leu Gly
1100 1105 1110
Phe Phe Pro Asp His Gln Leu Asp Pro Ala Phe Gly Ala Asn Ser
1115 1120 1125
Asn Asn Pro Asp Trp Asp Phe Asn Pro Asn Lys Asp His Trp Pro
1130 1135 1140
Glu Ala Asn Gln Val Gly Ala Gly Ala Phe Gly Pro Gly Phe Thr
1145 1150 1155
Pro Pro His Gly Gly Leu Leu Gly Trp Ser Pro Gln Ala Gln Gly
1160 1165 1170
Ile Leu Thr Thr Val Pro Ala Ala Pro Pro Pro Ala Ser Thr Asn
1175 1180 1185
Arg Gln Ser Gly Arg Gln Pro Thr Pro Ile Ser Pro Pro Leu Arg
1190 1195 1200
Asp Ser His Pro Gln Ala Met Gln Trp Asn Ser Thr Thr Phe His
1205 1210 1215
Gln Ala Leu Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala
1220 1225 1230
Gly Gly Ser Ser Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala
1235 1240 1245
Ser Pro Ile Ser Ser Ile Phe Ser Arg Thr Gly Asp Pro Ala Pro
1250 1255 1260
Asn Met Glu Asn Thr Thr Ser Gly Phe Leu Gly Pro Leu Leu Val
1265 1270 1275
Leu Gln Ala Gly Phe Phe Leu Leu Thr Arg Ile Leu Thr Ile Pro
1280 1285 1290
Gln Ser Leu Asp Ser Trp Trp Thr Ser Leu Asn Phe Leu Gly Gly
1295 1300 1305
Ala Pro Thr Cys Pro Gly Gln Asn Ser Gln Ser Pro Thr Ser Asn
1310 1315 1320
His Ser Pro Thr Ser Cys Pro Pro Ile Cys Pro Gly Tyr Arg Trp
1325 1330 1335
Met Cys Leu Arg Arg Phe Ile Ile Phe Leu Phe Ile Leu Leu Leu
1340 1345 1350
Cys Leu Ile Phe Leu Leu Val Leu Leu Asp Tyr Gln Gly Met Leu
1355 1360 1365
Pro Val Cys Pro Leu Leu Pro Gly Thr Ser Thr Thr Ser Thr Gly
1370 1375 1380
Pro Cys Lys Thr Cys Thr Ile Pro Ala Gln Gly Thr Ser Met Phe
1385 1390 1395
Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp Gly Asn Cys Thr Cys
1400 1405 1410
Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala Arg Phe Leu Trp Glu
1415 1420 1425
Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu Leu Val Pro Phe
1430 1435 1440
Val Gln Trp Phe Val Gly Leu Ser Pro Thr Val Trp Leu Ser Val
1445 1450 1455
Ile Trp Met Met Trp Tyr Trp Gly Pro Ser Leu Tyr Asn Ile Leu
1460 1465 1470
Ser Pro Phe Leu Pro Leu Leu Pro Ile Phe Phe Cys Leu Trp Val
1475 1480 1485
Tyr Ile
1490
<210> 13
<211> 1492
<212> PRT
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 13
Met Ser Leu Leu Trp Gly Gly Val Thr Val Leu Ala Ala Met Leu Ile
1 5 10 15
Ala Gly Gln Val Ala Ser Val Val Phe Leu Val Lys Gly Gly Gly Pro
20 25 30
Gly Gly Gly Met Gln Leu Phe His Leu Cys Leu Ile Ile Ser Cys Ser
35 40 45
Cys Pro Thr Val Gln Ala Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly
50 55 60
Met Asp Ile Asp Pro Tyr Lys Glu Phe Gly Ala Ser Val Glu Leu Leu
65 70 75 80
Ser Phe Leu Pro Ser Asp Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp
85 90 95
Thr Ala Ser Ala Leu Tyr Arg Glu Ala Leu Glu Ser Pro Glu His Cys
100 105 110
Ser Pro His His Thr Ala Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu
115 120 125
Leu Met Asn Leu Ala Thr Trp Val Gly Ser Asn Leu Glu Asp Pro Ala
130 135 140
Ser Arg Glu Leu Val Val Ser Tyr Val Asn Val Asn Met Gly Leu Lys
145 150 155 160
Ile Arg Gln Leu Leu Trp Phe His Ile Ser Cys Leu Thr Phe Gly Arg
165 170 175
Glu Thr Val Leu Glu Tyr Leu Val Ser Phe Gly Val Trp Ile Arg Thr
180 185 190
Pro Pro Ala Tyr Arg Pro Pro Asn Ala Pro Ile Leu Ser Thr Leu Pro
195 200 205
Glu Thr Thr Val Val Arg Arg Arg Gly Arg Ser Pro Arg Arg Arg Thr
210 215 220
Pro Ser Pro Arg Arg Arg Arg Ser Gln Ser Pro Arg Arg Arg Arg Ser
225 230 235 240
Gln Ser Arg Glu Ser Gln Cys Gly Gly Gly Ser Gly Gly Gly Met Pro
245 250 255
Leu Ser Tyr Gln His Phe Arg Lys Leu Leu Leu Leu Asp Asp Glu Ala
260 265 270
Gly Pro Leu Glu Glu Glu Leu Pro Arg Leu Ala Asp Glu Gly Leu Asn
275 280 285
Arg Arg Val Ala Glu Asp Leu Asn Leu Gly Asn Leu Asn Val Ser Ile
290 295 300
Pro Trp Thr His Lys Val Gly Asn Phe Thr Gly Leu Ala Ser Ser Thr
305 310 315 320
Val Pro Val Phe Asn Pro Glu Trp Gln Thr Pro Ser Phe Pro His Ile
325 330 335
His Leu Gln Glu Asp Ile Ile Asn Arg Cys Gln Gln Tyr Val Gly Pro
340 345 350
Leu Thr Val Asn Glu Lys Arg Arg Leu Lys Leu Ile Met Pro Ala Arg
355 360 365
Phe Tyr Pro Asn Leu Thr Lys Tyr Leu Pro Leu Asp Lys Gly Ile Lys
370 375 380
Pro Tyr Tyr Pro Glu His Ala Val Asn His Tyr Phe Lys Thr Arg His
385 390 395 400
Tyr Leu His Thr Leu Trp Lys Ala Gly Ile Leu Tyr Lys Arg Glu Thr
405 410 415
Thr Arg Ser Ala Ser Phe Cys Gly Ser Pro Tyr Ser Trp Glu Gln Glu
420 425 430
Leu Gln His Gly Arg Leu Val Phe Gln Thr Ser Thr Arg His Gly Asp
435 440 445
Glu Ser Phe Cys Ser Gln Ser Ser Gly Ile Leu Ser Arg Ser Pro Val
450 455 460
Gly Pro Cys Val Arg Ser Gln Leu Lys Gln Ser Arg Leu Gly Leu Gln
465 470 475 480
Pro Gln Gln Gly Ser Leu Ala Arg Gly Lys Ser Gly Arg Ser Gly Ser
485 490 495
Ile Arg Ala Arg Val His Pro Thr Thr Arg Arg Ser Phe Gly Val Glu
500 505 510
Pro Ser Gly Ser Gly His Ile Asp Asn Ser Ala Ser Ser Thr Ser Ser
515 520 525
Cys Leu His Gln Ser Ala Val Arg Lys Thr Ala Tyr Ser His Leu Ser
530 535 540
Thr Ser Lys Arg Gln Ser Ser Ser Gly His Ala Val Glu Leu His Asn
545 550 555 560
Ile Pro Pro Ser Ser Ala Arg Ser Gln Ser Glu Gly Pro Ile Phe Ser
565 570 575
Ala Trp Trp Leu Gln Phe Arg Asn Ser Lys Pro Ala Ser Asp Tyr Ala
580 585 590
Leu Thr His Ile Val Asn Leu Leu Glu Asp Trp Gly Pro Ala Thr Glu
595 600 605
His Gly Glu His Asn Ile Arg Ile Pro Arg Thr Pro Ala Arg Val Thr
610 615 620
Gly Gly Val Phe Leu Val Asp Lys Asn Pro His Asn Thr Thr Glu Ser
625 630 635 640
Arg Leu Val Val Asp Phe Ser Gln Phe Ser Arg Gly Ser Thr His Val
645 650 655
Ser Trp Pro Lys Phe Ala Val Pro Asn Leu Gln Ser Leu Thr Asn Leu
660 665 670
Leu Ser Ser Asn Leu Ser Thr Phe Gly Arg Lys Leu His Leu Tyr Ser
675 680 685
His Pro Ile Ile Leu Gly Phe Arg Lys Ile Pro Met Gly Val Gly Leu
690 695 700
Ser Pro Phe Leu Leu Ala Gln Phe Thr Ser Ala Ile Cys Ser Val Val
705 710 715 720
Arg Arg Ala Phe Pro His Cys Leu Ala Phe Ser Tyr Met Asp Asp Val
725 730 735
Val Leu Gly Ala Lys Ser Val Gln His Leu Glu Ser Leu Phe Thr Ser
740 745 750
Ile Thr Asn Phe Leu Leu Ser Leu Gly Ile His Leu Asn Pro Asn Lys
755 760 765
Thr Lys Arg Trp Gly Tyr Ser Leu Asn Phe Met Gly Tyr Val Ile Gly
770 775 780
Ser Trp Gly Thr Leu Pro Gln Glu His Ile Val Leu Lys Ile Lys Gln
785 790 795 800
Cys Phe Arg Lys Leu Pro Val Asn Arg Pro Ile Asp Trp Lys Val Cys
805 810 815
Gln Arg Ile Val Gly Leu Leu Gly Phe Ala Ala Pro Phe Thr Gln Cys
820 825 830
Gly Tyr Pro Ala Leu Met Pro Leu Tyr Ala Cys Ile Gln Ser Lys Gln
835 840 845
Ala Phe Thr Phe Ser Pro Thr Tyr Lys Ala Phe Leu Cys Lys Gln Tyr
850 855 860
Leu Asn Leu Tyr Pro Val Ala Arg Gln Arg Ser Gly Leu Cys Gln Val
865 870 875 880
Phe Ala Asp Ala Thr Pro Thr Gly Trp Gly Leu Ala Ile Gly His Arg
885 890 895
Ala Met Arg Gly Thr Phe Val Ala Pro Leu Pro Ile His Thr Ala Glu
900 905 910
Leu Leu Ala Ala Cys Phe Ala Arg Ser Arg Ser Gly Ala Lys Leu Ile
915 920 925
Gly Thr Asp Asn Ser Val Val Leu Ser Arg Lys Tyr Thr Ser Phe Pro
930 935 940
Trp Leu Leu Gly Cys Ala Ala Asn Trp Ile Leu Arg Gly Thr Ser Phe
945 950 955 960
Val Tyr Val Pro Ser Ala Leu Asn Pro Ala Ala Asp Pro Ser Ala Gly
965 970 975
Arg Leu Gly Leu Tyr Arg Pro Leu Leu His Leu Pro Phe Arg Pro Thr
980 985 990
Thr Gly Arg Thr Ser Leu Tyr Ala Val Ser Pro Ser Val Pro Ser His
995 1000 1005
Leu Pro Asp Arg Val His Phe Ala Ser Pro Leu His Val Ala Trp
1010 1015 1020
Arg Pro Pro Lys Ser Pro Asn Ser Asn Asn Pro Asp Trp Asp Phe
1025 1030 1035
Asn Pro Asn Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala
1040 1045 1050
Gly Ala Phe Gly Pro Gly Phe Thr Pro Pro His Gly Gly Leu Leu
1055 1060 1065
Gly Trp Ser Pro Gln Ala Gln Gly Ile Leu Thr Thr Val Pro Ala
1070 1075 1080
Ala Pro Pro Pro Ala Ser Thr Asn Arg Gln Ser Gly Arg Gln Pro
1085 1090 1095
Thr Pro Ile Ser Pro Pro Leu Arg Asp Ser His Pro Gln Ala Met
1100 1105 1110
Gln Trp Asn Ser Thr Thr Phe His Gln Ala Leu Leu Asp Pro Arg
1115 1120 1125
Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser Ser Gly Thr
1130 1135 1140
Val Asn Pro Val Pro Thr Thr Ala Ser Pro Ile Ser Ser Ile Phe
1145 1150 1155
Ser Arg Thr Gly Asp Pro Ala Pro Asn Gly Ser Lys Gly Lys Arg
1160 1165 1170
Lys Arg Arg Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu
1175 1180 1185
Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Met Gly Gly
1190 1195 1200
Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn Leu Ser Val
1205 1210 1215
Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu Asp Pro Ala
1220 1225 1230
Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro Asn
1235 1240 1245
Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Leu Glu Gly Gly
1250 1255 1260
Ser Gly Gly Met Glu Asn Thr Thr Ser Gly Phe Leu Gly Pro Leu
1265 1270 1275
Leu Val Leu Gln Ala Gly Phe Phe Leu Leu Thr Arg Ile Leu Thr
1280 1285 1290
Ile Pro Gln Ser Leu Asp Ser Trp Trp Thr Ser Leu Asn Phe Leu
1295 1300 1305
Gly Gly Ala Pro Thr Cys Pro Gly Gln Asn Ser Gln Ser Pro Thr
1310 1315 1320
Ser Asn His Ser Pro Thr Ser Cys Pro Pro Ile Cys Pro Gly Tyr
1325 1330 1335
Arg Trp Met Cys Leu Arg Arg Phe Ile Ile Phe Leu Phe Ile Leu
1340 1345 1350
Leu Leu Cys Leu Ile Phe Leu Leu Val Leu Leu Asp Tyr Gln Gly
1355 1360 1365
Met Leu Pro Val Cys Pro Leu Leu Pro Gly Thr Ser Thr Thr Ser
1370 1375 1380
Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala Gln Gly Thr Ser
1385 1390 1395
Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp Gly Asn Cys
1400 1405 1410
Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala Arg Phe Leu
1415 1420 1425
Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu Leu Val
1430 1435 1440
Pro Phe Val Gln Trp Phe Val Gly Leu Ser Pro Thr Val Trp Leu
1445 1450 1455
Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro Ser Leu Tyr Asn
1460 1465 1470
Ile Leu Ser Pro Phe Leu Pro Leu Leu Pro Ile Phe Phe Cys Leu
1475 1480 1485
Trp Val Tyr Ile
1490
<210> 14
<211> 4
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 14
Lys Gly Gly Ser
1
<210> 15
<211> 138
<212> PRT
<213> 乙型肝炎病毒
<400> 15
Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro Asn Lys Asp His Trp
1 5 10 15
Pro Glu Ala Asn Gln Val Gly Ala Gly Ala Phe Gly Pro Gly Phe Thr
20 25 30
Pro Pro His Gly Gly Leu Leu Gly Trp Ser Pro Gln Ala Gln Gly Ile
35 40 45
Leu Thr Thr Val Pro Ala Ala Pro Pro Pro Ala Ser Thr Asn Arg Gln
50 55 60
Ser Gly Arg Gln Pro Thr Pro Ile Ser Pro Pro Leu Arg Asp Ser His
65 70 75 80
Pro Gln Ala Met Gln Trp Asn Ser Thr Thr Phe His Gln Ala Leu Leu
85 90 95
Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser Ser
100 105 110
Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser Pro Ile Ser Ser Ile
115 120 125
Phe Ser Arg Thr Gly Asp Pro Ala Pro Asn
130 135
<210> 16
<211> 29
<212> PRT
<213> 乙型肝炎病毒
<400> 16
Met Gln Leu Phe His Leu Cys Leu Ile Ile Ser Cys Ser Cys Pro Thr
1 5 10 15
Val Gln Ala Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly
20 25
<210> 17
<211> 159
<212> PRT
<213> 乙型肝炎病毒
<400> 17
Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly Met Asp Ile Asp Pro Tyr
1 5 10 15
Lys Glu Phe Gly Ala Ser Val Glu Leu Leu Ser Phe Leu Pro Ser Asp
20 25 30
Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp Thr Ala Ser Ala Leu Tyr
35 40 45
Arg Glu Ala Leu Glu Ser Pro Glu His Cys Ser Pro His His Thr Ala
50 55 60
Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu Leu Met Asn Leu Ala Thr
65 70 75 80
Trp Val Gly Ser Asn Leu Glu Asp Pro Ala Ser Arg Glu Leu Val Val
85 90 95
Ser Tyr Val Asn Val Asn Met Gly Leu Lys Ile Arg Gln Leu Leu Trp
100 105 110
Phe His Ile Ser Cys Leu Thr Phe Gly Arg Glu Thr Val Leu Glu Tyr
115 120 125
Leu Val Ser Phe Gly Val Trp Ile Arg Thr Pro Pro Ala Tyr Arg Pro
130 135 140
Pro Asn Ala Pro Ile Leu Ser Thr Leu Pro Glu Thr Thr Val Val
145 150 155
<210> 18
<211> 226
<212> PRT
<213> 乙型肝炎病毒
<400> 18
Met Glu Asn Thr Thr Ser Gly Phe Leu Gly Pro Leu Leu Val Leu Gln
1 5 10 15
Ala Gly Phe Phe Leu Leu Thr Arg Ile Leu Thr Ile Pro Gln Ser Leu
20 25 30
Asp Ser Trp Trp Thr Ser Leu Asn Phe Leu Gly Gly Ala Pro Thr Cys
35 40 45
Pro Gly Gln Asn Ser Gln Ser Pro Thr Ser Asn His Ser Pro Thr Ser
50 55 60
Cys Pro Pro Ile Cys Pro Gly Tyr Arg Trp Met Cys Leu Arg Arg Phe
65 70 75 80
Ile Ile Phe Leu Phe Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu Val
85 90 95
Leu Leu Asp Tyr Gln Gly Met Leu Pro Val Cys Pro Leu Leu Pro Gly
100 105 110
Thr Ser Thr Thr Ser Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala
115 120 125
Gln Gly Thr Ser Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp
130 135 140
Gly Asn Cys Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala Arg
145 150 155 160
Phe Leu Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu Leu
165 170 175
Val Pro Phe Val Gln Trp Phe Val Gly Leu Ser Pro Thr Val Trp Leu
180 185 190
Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro Ser Leu Tyr Asn Ile
195 200 205
Leu Ser Pro Phe Leu Pro Leu Leu Pro Ile Phe Phe Cys Leu Trp Val
210 215 220
Tyr Ile
225
<210> 19
<211> 843
<212> PRT
<213> 乙型肝炎病毒
<400> 19
Met Pro Leu Ser Tyr Gln His Phe Arg Lys Leu Leu Leu Leu Asp Asp
1 5 10 15
Glu Ala Gly Pro Leu Glu Glu Glu Leu Pro Arg Leu Ala Asp Glu Gly
20 25 30
Leu Asn Arg Arg Val Ala Glu Asp Leu Asn Leu Gly Asn Leu Asn Val
35 40 45
Ser Ile Pro Trp Thr His Lys Val Gly Asn Phe Thr Gly Leu Tyr Ser
50 55 60
Ser Thr Val Pro Val Phe Asn Pro Glu Trp Gln Thr Pro Ser Phe Pro
65 70 75 80
His Ile His Leu Gln Glu Asp Ile Ile Asn Arg Cys Gln Gln Tyr Val
85 90 95
Gly Pro Leu Thr Val Asn Glu Lys Arg Arg Leu Lys Leu Ile Met Pro
100 105 110
Ala Arg Phe Tyr Pro Asn Leu Thr Lys Tyr Leu Pro Leu Asp Lys Gly
115 120 125
Ile Lys Pro Tyr Tyr Pro Glu His Ala Val Asn His Tyr Phe Lys Thr
130 135 140
Arg His Tyr Leu His Thr Leu Trp Lys Ala Gly Ile Leu Tyr Lys Arg
145 150 155 160
Glu Thr Thr Arg Ser Ala Ser Phe Cys Gly Ser Pro Tyr Ser Trp Glu
165 170 175
Gln Glu Leu Gln His Gly Arg Leu Val Phe Gln Thr Ser Thr Arg His
180 185 190
Gly Asp Glu Ser Phe Cys Ser Gln Ser Ser Gly Ile Leu Ser Arg Ser
195 200 205
Pro Val Gly Pro Cys Val Arg Ser Gln Leu Lys Gln Ser Arg Leu Gly
210 215 220
Leu Gln Pro Gln Gln Gly Ser Leu Ala Arg Gly Lys Ser Gly Arg Ser
225 230 235 240
Gly Ser Ile Arg Ala Arg Val His Pro Thr Thr Arg Arg Ser Phe Gly
245 250 255
Val Glu Pro Ser Gly Ser Gly His Ile Asp Asn Ser Ala Ser Ser Thr
260 265 270
Ser Ser Cys Leu His Gln Ser Ala Val Arg Lys Thr Ala Tyr Ser His
275 280 285
Leu Ser Thr Ser Lys Arg Gln Ser Ser Ser Gly His Ala Val Glu Leu
290 295 300
His Asn Ile Pro Pro Ser Ser Ala Arg Ser Gln Ser Glu Gly Pro Ile
305 310 315 320
Phe Ser Cys Trp Trp Leu Gln Phe Arg Asn Ser Lys Pro Cys Ser Asp
325 330 335
Tyr Cys Leu Thr His Ile Val Asn Leu Leu Glu Asp Trp Gly Pro Cys
340 345 350
Thr Glu His Gly Glu His Asn Ile Arg Ile Pro Arg Thr Pro Ala Arg
355 360 365
Val Thr Gly Gly Val Phe Leu Val Asp Lys Asn Pro His Asn Thr Thr
370 375 380
Glu Ser Arg Leu Val Val Asp Phe Ser Gln Phe Ser Arg Gly Ser Thr
385 390 395 400
His Val Ser Trp Pro Lys Phe Ala Val Pro Asn Leu Gln Ser Leu Thr
405 410 415
Asn Leu Leu Ser Ser Asn Leu Ser Trp Leu Ser Leu Asp Val Ser Ala
420 425 430
Ala Phe Tyr His Ile Pro Leu His Pro Ala Ala Met Pro His Leu Leu
435 440 445
Val Gly Ser Ser Gly Leu Pro Arg Tyr Val Ala Arg Leu Ser Ser Thr
450 455 460
Ser Arg Asn Ile Asn Tyr Gln His Gly Thr Met Gln Asp Leu His Asp
465 470 475 480
Ser Cys Ser Arg Asn Leu Tyr Val Ser Leu Leu Leu Leu Tyr Lys Thr
485 490 495
Phe Gly Arg Lys Leu His Leu Tyr Ser His Pro Ile Ile Leu Gly Phe
500 505 510
Arg Lys Ile Pro Met Gly Val Gly Leu Ser Pro Phe Leu Leu Ala Gln
515 520 525
Phe Thr Ser Ala Ile Cys Ser Val Val Arg Arg Ala Phe Pro His Cys
530 535 540
Leu Ala Phe Ser Tyr Met Asp Asp Val Val Leu Gly Ala Lys Ser Val
545 550 555 560
Gln His Leu Glu Ser Leu Phe Thr Ser Ile Thr Asn Phe Leu Leu Ser
565 570 575
Leu Gly Ile His Leu Asn Pro Asn Lys Thr Lys Arg Trp Gly Tyr Ser
580 585 590
Leu Asn Phe Met Gly Tyr Val Ile Gly Ser Trp Gly Thr Leu Pro Gln
595 600 605
Glu His Ile Val Leu Lys Ile Lys Gln Cys Phe Arg Lys Leu Pro Val
610 615 620
Asn Arg Pro Ile Asp Trp Lys Val Cys Gln Arg Ile Val Gly Leu Leu
625 630 635 640
Gly Phe Ala Ala Pro Phe Thr Gln Cys Gly Tyr Pro Ala Leu Met Pro
645 650 655
Leu Tyr Ala Cys Ile Gln Ser Lys Gln Ala Phe Thr Phe Ser Pro Thr
660 665 670
Tyr Lys Ala Phe Leu Cys Lys Gln Tyr Leu Asn Leu Tyr Pro Val Ala
675 680 685
Arg Gln Arg Ser Gly Leu Cys Gln Val Phe Ala Asp Ala Thr Pro Thr
690 695 700
Gly Trp Gly Leu Ala Ile Gly His Arg Arg Met Arg Gly Thr Phe Val
705 710 715 720
Ala Pro Leu Pro Ile His Thr Ala Glu Leu Leu Ala Ala Cys Phe Ala
725 730 735
Arg Ser Arg Ser Gly Ala Lys Leu Ile Gly Thr Asp Asn Ser Val Val
740 745 750
Leu Ser Arg Lys Tyr Thr Ser Phe Pro Trp Leu Leu Gly Cys Ala Ala
755 760 765
Asn Trp Ile Leu Arg Gly Thr Ser Phe Val Tyr Val Pro Ser Ala Leu
770 775 780
Asn Pro Ala Asp Asp Pro Ser Arg Gly Arg Leu Gly Leu Tyr Arg Pro
785 790 795 800
Leu Leu His Leu Pro Phe Arg Pro Thr Thr Gly Arg Thr Ser Leu Tyr
805 810 815
Ala Val Ser Pro Ser Val Pro Ser His Leu Pro Asp Arg Val His Phe
820 825 830
Ala Ser Pro Leu His Val Ala Trp Arg Pro Pro
835 840
<210> 20
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 20
Gly Ser Lys Gly Lys
1 5
<210> 21
<211> 59
<212> PRT
<213> 乙型肝炎病毒
<400> 21
Met Gly Gly Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn Leu
1 5 10 15
Ser Val Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu Asp Pro
20 25 30
Ala Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro Asn
35 40 45
Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly
50 55
<210> 22
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 22
Leu Glu Gly Gly Ser Gly Gly
1 5
<210> 23
<211> 1539
<212> PRT
<213> 乙型肝炎病毒
<400> 23
Met Ser Leu Leu Trp Gly Gly Val Thr Val Leu Ala Ala Met Leu Ile
1 5 10 15
Ala Gly Gln Val Ala Ser Val Val Phe Leu Val Ser Lys Ser Gly Pro
20 25 30
Pro Ser Gly Lys Ser Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro
35 40 45
Asn Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala Gly Ala Phe
50 55 60
Gly Pro Gly Phe Thr Pro Pro His Gly Gly Leu Leu Gly Trp Ser Pro
65 70 75 80
Gln Ala Gln Gly Ile Leu Thr Thr Val Pro Ala Ala Pro Pro Pro Ala
85 90 95
Ser Thr Asn Arg Gln Ser Gly Arg Gln Pro Thr Pro Ile Ser Pro Pro
100 105 110
Leu Arg Asp Ser His Pro Gln Ala Met Gln Trp Asn Ser Thr Thr Phe
115 120 125
His Gln Ala Leu Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala
130 135 140
Gly Gly Ser Ser Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser
145 150 155 160
Pro Ile Ser Ser Ile Phe Ser Arg Thr Gly Asp Pro Ala Pro Asn Gly
165 170 175
Ser Lys Ser Gly Ser Lys Met Pro Leu Ser Tyr Gln His Phe Arg Lys
180 185 190
Leu Leu Leu Leu Asp Asp Glu Ala Gly Pro Leu Glu Glu Glu Leu Pro
195 200 205
Arg Leu Ala Asp Glu Gly Leu Asn Arg Arg Val Ala Glu Asp Leu Asn
210 215 220
Leu Gly Asn Leu Asn Val Ser Ile Pro Trp Thr His Lys Val Gly Asn
225 230 235 240
Phe Thr Gly Leu Ala Ser Ser Thr Val Pro Val Phe Asn Pro Glu Trp
245 250 255
Gln Thr Pro Ser Phe Pro His Ile His Leu Gln Glu Asp Ile Ile Asn
260 265 270
Arg Cys Gln Gln Tyr Val Gly Pro Leu Thr Val Asn Glu Lys Arg Arg
275 280 285
Leu Lys Leu Ile Met Pro Ala Arg Phe Tyr Pro Asn Leu Thr Lys Tyr
290 295 300
Leu Pro Leu Asp Lys Gly Ile Lys Pro Tyr Tyr Pro Glu His Ala Val
305 310 315 320
Asn His Tyr Phe Lys Thr Arg His Tyr Leu His Thr Leu Trp Lys Ala
325 330 335
Gly Ile Leu Tyr Lys Arg Glu Thr Thr Arg Ser Ala Ser Phe Cys Gly
340 345 350
Ser Pro Tyr Ser Trp Glu Gln Glu Leu Gln His Gly Arg Leu Val Phe
355 360 365
Gln Thr Ser Thr Arg His Gly Asp Glu Ser Phe Cys Ser Gln Ser Ser
370 375 380
Gly Ile Leu Ser Arg Ser Pro Val Gly Pro Cys Val Arg Ser Gln Leu
385 390 395 400
Lys Gln Ser Arg Leu Gly Leu Gln Pro Gln Gln Gly Ser Leu Ala Arg
405 410 415
Gly Lys Ser Gly Arg Ser Gly Ser Ile Arg Ala Arg Val His Pro Thr
420 425 430
Thr Arg Arg Ser Phe Gly Val Glu Pro Ser Gly Ser Gly His Ile Asp
435 440 445
Asn Ser Ala Ser Ser Thr Ser Ser Cys Leu His Gln Ser Ala Val Arg
450 455 460
Lys Thr Ala Tyr Ser His Leu Ser Thr Ser Lys Arg Gln Ser Ser Ser
465 470 475 480
Gly His Ala Val Glu Leu His Asn Ile Pro Pro Ser Ser Ala Arg Ser
485 490 495
Gln Ser Glu Gly Pro Ile Phe Ser Ala Trp Trp Leu Gln Phe Arg Asn
500 505 510
Ser Lys Pro Ala Ser Asp Tyr Ala Leu Thr His Ile Val Asn Leu Leu
515 520 525
Glu Asp Trp Gly Pro Ala Thr Glu His Gly Glu His Asn Ile Arg Ile
530 535 540
Pro Arg Thr Pro Ala Arg Val Thr Gly Gly Val Phe Leu Val Asp Lys
545 550 555 560
Asn Pro His Asn Thr Thr Glu Ser Arg Leu Val Val Asp Phe Ser Gln
565 570 575
Phe Ser Arg Gly Ser Thr His Val Ser Trp Pro Lys Phe Ala Val Pro
580 585 590
Asn Leu Gln Ser Leu Thr Asn Leu Leu Ser Ser Asn Leu Ser Trp Leu
595 600 605
Ser Leu Asp Val Ser Ala Ala Phe Tyr His Ile Pro Leu His Pro Ala
610 615 620
Ala Met Pro His Leu Leu Val Gly Ser Ser Gly Leu Pro Arg Tyr Val
625 630 635 640
Ala Arg Leu Ser Ser Thr Ser Arg Asn Ile Asn Tyr Gln His Gly Thr
645 650 655
Met Gln Asp Leu His Asp Ser Cys Ser Arg Asn Leu Tyr Val Ser Leu
660 665 670
Leu Leu Leu Tyr Lys Thr Phe Gly Arg Lys Leu His Leu Tyr Ser His
675 680 685
Pro Ile Ile Leu Gly Phe Arg Lys Ile Pro Met Gly Val Gly Leu Ser
690 695 700
Pro Phe Leu Leu Ala Gln Phe Thr Ser Ala Ile Cys Ser Val Val Arg
705 710 715 720
Arg Ala Phe Pro His Cys Leu Ala Phe Ser Tyr Met Asp Asp Val Val
725 730 735
Leu Gly Ala Lys Ser Val Gln His Leu Glu Ser Leu Phe Thr Ser Ile
740 745 750
Thr Asn Phe Leu Leu Ser Leu Gly Ile His Leu Asn Pro Asn Lys Thr
755 760 765
Lys Arg Trp Gly Tyr Ser Leu Asn Phe Met Gly Tyr Val Ile Gly Ser
770 775 780
Trp Gly Thr Leu Pro Gln Glu His Ile Val Leu Lys Ile Lys Gln Cys
785 790 795 800
Phe Arg Lys Leu Pro Val Asn Arg Pro Ile Asp Trp Lys Val Cys Gln
805 810 815
Arg Ile Val Gly Leu Leu Gly Phe Ala Ala Pro Phe Thr Gln Cys Gly
820 825 830
Tyr Pro Ala Leu Met Pro Leu Tyr Ala Cys Ile Gln Ser Lys Gln Ala
835 840 845
Phe Thr Phe Ser Pro Thr Tyr Lys Ala Phe Leu Cys Lys Gln Tyr Leu
850 855 860
Asn Leu Tyr Pro Val Ala Arg Gln Arg Ser Gly Leu Cys Gln Val Phe
865 870 875 880
Ala Asp Ala Thr Pro Thr Gly Trp Gly Leu Ala Ile Gly His Arg Ala
885 890 895
Met Arg Gly Thr Phe Val Ala Pro Leu Pro Ile His Thr Ala Glu Leu
900 905 910
Leu Ala Ala Cys Phe Ala Arg Ser Arg Ser Gly Ala Lys Leu Ile Gly
915 920 925
Thr Asp Asn Ser Val Val Leu Ser Arg Lys Tyr Thr Ser Phe Pro Trp
930 935 940
Leu Leu Gly Cys Ala Ala Asn Trp Ile Leu Arg Gly Thr Ser Phe Val
945 950 955 960
Tyr Val Pro Ser Ala Leu Asn Pro Ala Ala Asp Pro Ser Ala Gly Arg
965 970 975
Leu Gly Leu Tyr Arg Pro Leu Leu His Leu Pro Phe Arg Pro Thr Thr
980 985 990
Gly Arg Thr Ser Leu Tyr Ala Val Ser Pro Ser Val Pro Ser His Leu
995 1000 1005
Pro Asp Arg Val His Phe Ala Ser Pro Leu His Val Ala Trp Arg
1010 1015 1020
Pro Pro Ser Lys Ser Pro Gly Ser Gly Pro Pro Met Gln Leu Phe
1025 1030 1035
His Leu Cys Leu Ile Ile Ser Cys Ser Cys Pro Thr Val Gln Ala
1040 1045 1050
Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly Met Asp Ile Asp Pro
1055 1060 1065
Tyr Lys Glu Phe Gly Ala Ser Val Glu Leu Leu Ser Phe Leu Pro
1070 1075 1080
Ser Asp Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp Thr Ala Ser
1085 1090 1095
Ala Leu Tyr Arg Glu Ala Leu Glu Ser Pro Glu His Cys Ser Pro
1100 1105 1110
His His Thr Ala Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu Leu
1115 1120 1125
Met Asn Leu Ala Thr Trp Val Gly Ser Asn Leu Glu Asp Pro Ala
1130 1135 1140
Ser Arg Glu Leu Val Val Ser Tyr Val Asn Val Asn Met Gly Leu
1145 1150 1155
Lys Ile Arg Gln Leu Leu Trp Phe His Ile Ser Cys Leu Thr Phe
1160 1165 1170
Gly Arg Glu Thr Val Leu Glu Tyr Leu Val Ser Phe Gly Val Trp
1175 1180 1185
Ile Arg Thr Pro Pro Ala Tyr Arg Pro Pro Asn Ala Pro Ile Leu
1190 1195 1200
Ser Thr Leu Pro Glu Thr Thr Val Val Arg Arg Arg Gly Arg Ser
1205 1210 1215
Pro Arg Arg Arg Thr Pro Ser Pro Arg Arg Arg Arg Ser Gln Ser
1220 1225 1230
Pro Arg Arg Arg Arg Ser Gln Ser Arg Glu Ser Gln Cys Met Gly
1235 1240 1245
Gly Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn Leu Ser
1250 1255 1260
Val Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu Asp Pro
1265 1270 1275
Ala Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro
1280 1285 1290
Asn Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala Ser Lys
1295 1300 1305
Gly Gly Lys Ser Gly Met Glu Asn Thr Thr Ser Gly Phe Leu Gly
1310 1315 1320
Pro Leu Leu Val Leu Gln Ala Gly Phe Phe Leu Leu Thr Arg Ile
1325 1330 1335
Leu Thr Ile Pro Gln Ser Leu Asp Ser Trp Trp Thr Ser Leu Asn
1340 1345 1350
Phe Leu Gly Gly Ala Pro Thr Cys Pro Gly Gln Asn Ser Gln Ser
1355 1360 1365
Pro Thr Ser Asn His Ser Pro Thr Ser Cys Pro Pro Ile Cys Pro
1370 1375 1380
Gly Tyr Arg Trp Met Cys Leu Arg Arg Phe Ile Ile Phe Leu Phe
1385 1390 1395
Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu Val Leu Leu Asp Tyr
1400 1405 1410
Gln Gly Met Leu Pro Val Cys Pro Leu Leu Pro Gly Thr Ser Thr
1415 1420 1425
Thr Ser Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala Gln Gly
1430 1435 1440
Thr Ser Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp Gly
1445 1450 1455
Asn Cys Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala Arg
1460 1465 1470
Phe Leu Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu
1475 1480 1485
Leu Val Pro Phe Val Gln Trp Phe Val Gly Leu Ser Pro Thr Val
1490 1495 1500
Trp Leu Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro Ser Leu
1505 1510 1515
Tyr Asn Ile Leu Ser Pro Phe Leu Pro Leu Leu Pro Ile Phe Phe
1520 1525 1530
Cys Leu Trp Val Tyr Ile
1535
<210> 24
<211> 7143
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 24
gtaatctatt cgatataccg ttgctaacag tatactggcc caataactgt ggatggaaaa 60
tctataataa tacattaata tcatccgatg gtgctagggt tatttggatg gatgcgtata 120
aattttcttg cggtttatct ttacaagact attgttatca ttggggtagc aaaccagaga 180
gccgaccatt cgatttaata aaaaaatcag atgctaaacg caattctaaa tcgttggtca 240
aagaatctat ggcatccttg aaatccttgt acgaggcatt cgagacacaa tcaggagcgt 300
tagaagtttt aatgagtcca tgtaggatgt tttcgttttc tagaatagaa gacatgttct 360
taactagtgt cattaataga gtatccgaga atactggaat ggggatgtat tatcctacca 420
acgatatacc ttctctattt atcgaatcat ctatctgtct agattatatt atagtaaata 480
atcaggaatc caacaaatat cgtatcaaat ctgttctcga tatcatttct tcaaaacaat 540
accctgcagg acgtcccaac tacgttaaaa atggtacaaa aggaaagtta tatatcgcgt 600
tgtgtaaagt taccgtacct actaacgacc atattccagt agtttatcac gatgatgaca 660
atactaccac ctttattaca gtattgacgt ccgtcgatat tgaaactgct atcagagcag 720
gatattcgat agtcgaatta ggggctttac aatgggataa taatattcca gaacttaaaa 780
acggtttact ggatagtatc aagatgattt atgacttgaa cgcagttaca acaaataatt 840
tattggaaca gctcatagaa aatattaact ttaacaactc tagtataatt tcgttgtttt 900
atacatttgc cattagttat tgccgagcat tcatttactc aattatggaa accatagatc 960
cggtgtatat atctcagttc agttataaag aattatacgt tagtagctct tataaagata 1020
ttaatgaatc catgagtcag atggtaaaat tataaaaagt gaaaaacaat attattttta 1080
tcgttggttg ttacactatg tctctgctgt ggggcggagt gacagtgctg gccgctatgc 1140
tgattgctgg acaggtggcc agcgtggtgt tcctggtgtc taagtctgga cctcctagcg 1200
gcaagagcaa cagcaacaac cccgactggg acttcaaccc caacaaggac cattggccag 1260
aggccaatca agtcggagcc ggcgcttttg gccctggctt tacacctcct catggcggac 1320
tgcttggatg gtcacctcag gctcagggca tcctgacaac agtgcctgct gctccacctc 1380
ctgccagcac caatagacag tctggcagac agcccacacc tatcagccct ccactgagag 1440
acagccatcc tcaggccatg cagtggaaca gcaccacctt tcatcaggcc ctgctggacc 1500
ctagagtgcg gggcctttat tttcctgccg gcggatctag cagcggcacc gtgaatcctg 1560
tgcctacaac cgcctctcct atcagcagca tcttcagcag aaccggcgat cccgctccta 1620
acggcagcaa gtctggctcc aagatgcccc tgagctacca gcacttcaga aaactgctgc 1680
tgctggacga cgaggccgga cctctggaag aagaactgcc tagactggcc gacgagggcc 1740
tgaatagaag agtggccgag gacctgaacc tgggcaacct gaatgtgtct atcccctgga 1800
cacacaaagt gggcaacttc acaggcctgg ccagctctac cgtgcctgtg ttcaatcccg 1860
agtggcagac ccctagcttc cctcacatcc atctgcaaga ggacatcatc aaccggtgcc 1920
agcagtacgt gggccctctg accgtgaacg agaagcggag actgaagctg atcatgcccg 1980
ccagattcta ccccaacctg accaagtacc tgcctctgga caagggcatc aagccttact 2040
accctgagca cgccgtgaac cactacttca agacccggca ctacctgcac accctgtgga 2100
aggccggcat cctgtataag agagagacaa ccagaagcgc cagcttctgc ggcagccctt 2160
actcttggga gcaagagctg cagcacggca gactggtgtt ccagacctct acaagacacg 2220
gcgacgagtc tttctgcagc cagagcagcg gaatcctgag cagatctcct gtgggacctt 2280
gtgtgcggag ccagctgaaa cagagtagac tgggcctgca gcctcagcag ggatctctgg 2340
ctagaggaaa gagcggcaga agcggcagca tcagagccag agtgcaccct accaccagaa 2400
gaagctttgg cgtcgagcct agcggctccg gccacatcga taatagcgcc agcagcacca 2460
gcagctgcct gcatcagtcc gccgttagaa agaccgccta cagccacctg agcacctcca 2520
agagacagag cagctctgga cacgccgtgg aactgcacaa catccctcca agcagcgcca 2580
gatctcagag cgagggccct atcttttctg cctggtggct gcagttcaga aacagcaagc 2640
ccgccagcga ctacgccctg acacacatcg tgaacctgct ggaagattgg ggccctgcca 2700
cagaacacgg cgagcacaat atcagaatcc ccagaacacc cgccagagtg acaggcggag 2760
tgtttctggt ggacaagaac cctcacaaca ccaccgagag caggctggtg gtggacttca 2820
gccagtttag cagaggcagc acccacgtgt cctggcctaa attcgccgtg cctaacctgc 2880
agagcctgac caatctgctg agcagcaacc tgagctggct gagcctggat gtgtccgccg 2940
ccttctatca catcccactg catcctgccg ccatgcctca tctgcttgtg ggaagttctg 3000
gcctgcctag atacgtggcc aggctgtcct ctaccagccg gaacatcaat taccagcacg 3060
ggaccatgca ggacctgcac gacagctgta gccggaacct gtacgttagc ctgctcctgc 3120
tgtacaagac cttcggcaga aagctgcacc tgtactctca ccccatcatc ctgggcttca 3180
gaaagatccc catgggcgtg ggcctgtctc catttctgct ggcccagttt accagcgcca 3240
tctgctctgt tgtgcggaga gcctttcctc actgcctggc cttcagctac atggacgatg 3300
tggtgctggg cgccaagtct gtgcagcacc tggaaagcct gtttacctcc atcaccaact 3360
ttctgctgtc cctgggaatc catctgaacc ctaacaagac caagagatgg ggctacagcc 3420
tgaacttcat gggctacgtg atcggcagct ggggcacact gcctcaagag cacatcgtgc 3480
tgaaaatcaa gcagtgcttt cggaagctgc ccgtgaacag acccatcgac tggaaagtgt 3540
gccagcggat cgttggcctg ctgggatttg ccgctccttt cacacagtgc ggctaccccg 3600
ctctcatgcc tctgtatgcc tgtatccaga gcaagcaggc cttcacattc agccctacct 3660
acaaggcctt cctgtgcaag cagtacctga atctgtaccc cgtggccaga cagagaagcg 3720
gcctgtgtca agtgttcgcc gatgccacac ctacaggatg gggactcgcc attggacaca 3780
gggccatgag aggaaccttt gtggcccctc tgcctatcca cacagccgaa ttgctggctg 3840
cctgcttcgc cagaagtaga tccggcgcca agctgatcgg caccgacaat tctgtggtcc 3900
tgagccggaa gtacaccagc tttccatggc tgctgggctg tgccgccaac tggattctga 3960
gaggcaccag cttcgtgtac gtgcccagcg ctcttaaccc tgccgctgat ccttctgctg 4020
ggagactcgg cctgtacaga cctctgctgc atctgccctt cagacccacc acaggcagaa 4080
ccagcctgta tgccgtgtct cctagcgtgc caagccatct gcctgatcgg gtgcactttg 4140
cctctccact tcatgtggct tggcggccac ctagcaagag ccctggatct ggaccaccta 4200
tgcagctgtt tcacctgtgc ctgatcatct cttgcagctg ccctacagtg caggccagca 4260
agctgtgtct cggatggctc tggggcatgg acatcgaccc ctacaaagaa ttcggcgcca 4320
gcgtcgagct gctgagcttc ctgcctagcg acttcttccc ctccatccgg gatctgctgg 4380
atactgctag cgccctgtat cgcgaggccc tggaatctcc tgagcactgt tctccacacc 4440
acactgccct gagacaggct atcctgtgtt ggggcgagct gatgaacctg gccacatggg 4500
tcggaagcaa cctggaagat cccgccagca gagaactggt ggtgtcctac gtgaacgtga 4560
acatgggcct gaagatcaga cagctgctgt ggttccacat ctcctgcctg acctttggcc 4620
gggaaaccgt gctggaatac ctggtgtcct ttggcgtgtg gatcagaacc cctccagcct 4680
accgacctcc taacgctcct atcctgtcta ccctgcctga gacaacagtc gtgcggcgga 4740
gaggaagaag ccctagaaga aggaccccat ctcctcggcg gagaagatca cagtcccctc 4800
ggagaagaag atcccagagc cgggaatccc agtgctgatt tttgttcgac attaaaaatt 4860
gaaaataaat acaaaggttc ttgagggttg tgttaaattg aaagcgagaa ataatcataa 4920
atatgattca ggtgacggat ccatgggagg ctggtccagc aaacccagac aaggcatggg 4980
caccaatctg agcgtgccca atcctctggg attcttccca gaccaccagc tggatcctgc 5040
cttcggcgcc aacagcaaca accccgactg ggacttcaac cccaacaagg accattggcc 5100
agaggccaat caagtgggcg ctagcaaagg cggcaagagc ggcatggaga ataccacctc 5160
tggctttctg ggccctctgc tggttctgca ggccggcttc tttctgctga cccggatcct 5220
gacaatccct cagagcctgg atagctggtg gacaagcctg aacttccttg gcggcgctcc 5280
tacatgccct ggccagaatt ctcagagccc caccagcaat cacagcccca caagctgccc 5340
tccaatctgc cctggctaca gatggatgtg cctgcggcgg ttcatcatct ttctgttcat 5400
cctgctgctg tgcctgatct tcctgctggt gctgctggac tatcagggca tgctgcctgt 5460
gtgtcctctg ctgcctggca ccagcacaac atctacaggc ccttgcaaga cctgcacaat 5520
cccagctcag ggcacctcca tgtttcccag ctgctgttgc accaagccta gcgacggcaa 5580
ctgcacatgc atccccattc cttccagctg ggccttcgcc agatttctgt gggaatgggc 5640
cagcgtgcgg ttcagctggc tgtctctgct tgtgcctttc gtgcagtggt tcgtgggcct 5700
gtctcctaca gtgtggctga gcgtgatctg gatgatgtgg tactggggcc ctagcctgta 5760
caatattctg agccccttcc tgcctctgct cccaatcttc ttctgcctgt gggtgtacat 5820
ctgattaacc gagtttctgc attattgtaa ttcgtatgct ggcaccatca aagaatcact 5880
tctaaaagat atcaatatca cacatacaaa tattactacc ctattgaatg agacagccaa 5940
ggttatcaag ttagtaaaat ctctggtaga taaagaagat actgatattg tgaataattt 6000
cattaccaaa gaaattaaaa acagagacaa aatagttaat agtttgtctc tatcaaacct 6060
ggactttcgt ttgtaaattg gggctttttg tacaataaat gggtgttgcc aatgattcat 6120
cccctgaata tcaatggatg tctccccata gattatcaga tactgttata ttaggagact 6180
gtttgtattt taacaatata atgtcccaat tagatttaca ccaaaattgg gctccatcag 6240
ttagattgtt aaattatttt aagaatttta ataaggaaac actactaaag atagaagaga 6300
atgattacat taattcatcc tttttccaac aaaaggataa acgattttat cctataaacg 6360
acgattttta tcacatatct acaggaggat atggtatagt ctttaagata gataactatg 6420
tagtaaaatt tgtattcgag gccacaaaat tatatagtcc catggaaact acggcggagt 6480
tcacagtacc caaatttcta tacaacaatc taaagggaga tgaaaaaaaa ttaatcgtgt 6540
gtgcgtgggc catgggatta aactataaat taacattttt acatactctg tataaacgtg 6600
ttcttcatat gttgctatta ttgatacaaa ctatggatgg tcaggaacta tcattgagat 6660
attcttctaa agttttttta aaggcgttta acgagagaaa ggacagtatc aaattcgtga 6720
aattactatc ccacttttat ccggcagtta ttaacagtaa tattaatgtt ataaactatt 6780
ttaaccgcat gtttcacttt ttcgaacatg aaaagagaac taactacgaa tacgaaagag 6840
gaaatattat aatttttccc ctagcactgt attcggcaga taaagtagat accgagctag 6900
ctatcaaatt aggatttaaa tctttggtac aatacataaa gtttatcttt ttacagatgg 6960
ctctgttata cattaaaatt tacgaactac catgctgcga caacttttta cacgcagatc 7020
ttaaacccga taatatctta ctttttgatt ccaatgaacc aataataatt catctaaagg 7080
ataaaaagtt tgtttttaat gaacgtatta aatcggcatt aaacgacttt gacttttccc 7140
aag 7143
<210> 25
<211> 1524
<212> PRT
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 25
Met Ser Leu Leu Trp Gly Gly Val Thr Val Leu Ala Ala Met Leu Ile
1 5 10 15
Ala Gly Gln Val Ala Ser Val Val Phe Leu Val Lys Gly Gly Gly Pro
20 25 30
Gly Gly Gly Met Gln Leu Phe His Leu Cys Leu Ile Ile Ser Cys Ser
35 40 45
Cys Pro Thr Val Gln Ala Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly
50 55 60
Met Asp Ile Asp Pro Tyr Lys Glu Phe Gly Ala Ser Val Glu Leu Leu
65 70 75 80
Ser Phe Leu Pro Ser Asp Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp
85 90 95
Thr Ala Ser Ala Leu Tyr Arg Glu Ala Leu Glu Ser Pro Glu His Cys
100 105 110
Ser Pro His His Thr Ala Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu
115 120 125
Leu Met Asn Leu Ala Thr Trp Val Gly Ser Asn Leu Glu Asp Pro Ala
130 135 140
Ser Arg Glu Leu Val Val Ser Tyr Val Asn Val Asn Met Gly Leu Lys
145 150 155 160
Ile Arg Gln Leu Leu Trp Phe His Ile Ser Cys Leu Thr Phe Gly Arg
165 170 175
Glu Thr Val Leu Glu Tyr Leu Val Ser Phe Gly Val Trp Ile Arg Thr
180 185 190
Pro Pro Ala Tyr Arg Pro Pro Asn Ala Pro Ile Leu Ser Thr Leu Pro
195 200 205
Glu Thr Thr Val Val Arg Arg Arg Gly Arg Ser Pro Arg Arg Arg Thr
210 215 220
Pro Ser Pro Arg Arg Arg Arg Ser Gln Ser Pro Arg Arg Arg Arg Ser
225 230 235 240
Gln Ser Arg Glu Ser Gln Cys Gly Gly Gly Ser Gly Gly Gly Met Pro
245 250 255
Leu Ser Tyr Gln His Phe Arg Lys Leu Leu Leu Leu Asp Asp Glu Ala
260 265 270
Gly Pro Leu Glu Glu Glu Leu Pro Arg Leu Ala Asp Glu Gly Leu Asn
275 280 285
Arg Arg Val Ala Glu Asp Leu Asn Leu Gly Asn Leu Asn Val Ser Ile
290 295 300
Pro Trp Thr His Lys Val Gly Asn Phe Thr Gly Leu Ala Ser Ser Thr
305 310 315 320
Val Pro Val Phe Asn Pro Glu Trp Gln Thr Pro Ser Phe Pro His Ile
325 330 335
His Leu Gln Glu Asp Ile Ile Asn Arg Cys Gln Gln Tyr Val Gly Pro
340 345 350
Leu Thr Val Asn Glu Lys Arg Arg Leu Lys Leu Ile Met Pro Ala Arg
355 360 365
Phe Tyr Pro Asn Leu Thr Lys Tyr Leu Pro Leu Asp Lys Gly Ile Lys
370 375 380
Pro Tyr Tyr Pro Glu His Ala Val Asn His Tyr Phe Lys Thr Arg His
385 390 395 400
Tyr Leu His Thr Leu Trp Lys Ala Gly Ile Leu Tyr Lys Arg Glu Thr
405 410 415
Thr Arg Ser Ala Ser Phe Cys Gly Ser Pro Tyr Ser Trp Glu Gln Glu
420 425 430
Leu Gln His Gly Arg Leu Val Phe Gln Thr Ser Thr Arg His Gly Asp
435 440 445
Glu Ser Phe Cys Ser Gln Ser Ser Gly Ile Leu Ser Arg Ser Pro Val
450 455 460
Gly Pro Cys Val Arg Ser Gln Leu Lys Gln Ser Arg Leu Gly Leu Gln
465 470 475 480
Pro Gln Gln Gly Ser Leu Ala Arg Gly Lys Ser Gly Arg Ser Gly Ser
485 490 495
Ile Arg Ala Arg Val His Pro Thr Thr Arg Arg Ser Phe Gly Val Glu
500 505 510
Pro Ser Gly Ser Gly His Ile Asp Asn Ser Ala Ser Ser Thr Ser Ser
515 520 525
Cys Leu His Gln Ser Ala Val Arg Lys Thr Ala Tyr Ser His Leu Ser
530 535 540
Thr Ser Lys Arg Gln Ser Ser Ser Gly His Ala Val Glu Leu His Asn
545 550 555 560
Ile Pro Pro Ser Ser Ala Arg Ser Gln Ser Glu Gly Pro Ile Phe Ser
565 570 575
Ala Trp Trp Leu Gln Phe Arg Asn Ser Lys Pro Ala Ser Asp Tyr Ala
580 585 590
Leu Thr His Ile Val Asn Leu Leu Glu Asp Trp Gly Pro Ala Thr Glu
595 600 605
His Gly Glu His Asn Ile Arg Ile Pro Arg Thr Pro Ala Arg Val Thr
610 615 620
Gly Gly Val Phe Leu Val Asp Lys Asn Pro His Asn Thr Thr Glu Ser
625 630 635 640
Arg Leu Val Val Asp Phe Ser Gln Phe Ser Arg Gly Ser Thr His Val
645 650 655
Ser Trp Pro Lys Phe Ala Val Pro Asn Leu Gln Ser Leu Thr Asn Leu
660 665 670
Leu Ser Ser Asn Leu Ser Thr Phe Gly Arg Lys Leu His Leu Tyr Ser
675 680 685
His Pro Ile Ile Leu Gly Phe Arg Lys Ile Pro Met Gly Val Gly Leu
690 695 700
Ser Pro Phe Leu Leu Ala Gln Phe Thr Ser Ala Ile Cys Ser Val Val
705 710 715 720
Arg Arg Ala Phe Pro His Cys Leu Ala Phe Ser Tyr Met Asp Asp Val
725 730 735
Val Leu Gly Ala Lys Ser Val Gln His Leu Glu Ser Leu Phe Thr Ser
740 745 750
Ile Thr Asn Phe Leu Leu Ser Leu Gly Ile His Leu Asn Pro Asn Lys
755 760 765
Thr Lys Arg Trp Gly Tyr Ser Leu Asn Phe Met Gly Tyr Val Ile Gly
770 775 780
Ser Trp Gly Thr Leu Pro Gln Glu His Ile Val Leu Lys Ile Lys Gln
785 790 795 800
Cys Phe Arg Lys Leu Pro Val Asn Arg Pro Ile Asp Trp Lys Val Cys
805 810 815
Gln Arg Ile Val Gly Leu Leu Gly Phe Ala Ala Pro Phe Thr Gln Cys
820 825 830
Gly Tyr Pro Ala Leu Met Pro Leu Tyr Ala Cys Ile Gln Ser Lys Gln
835 840 845
Ala Phe Thr Phe Ser Pro Thr Tyr Lys Ala Phe Leu Cys Lys Gln Tyr
850 855 860
Leu Asn Leu Tyr Pro Val Ala Arg Gln Arg Ser Gly Leu Cys Gln Val
865 870 875 880
Phe Ala Asp Ala Thr Pro Thr Gly Trp Gly Leu Ala Ile Gly His Arg
885 890 895
Ala Met Arg Gly Thr Phe Val Ala Pro Leu Pro Ile His Thr Ala Glu
900 905 910
Leu Leu Ala Ala Cys Phe Ala Arg Ser Arg Ser Gly Ala Lys Leu Ile
915 920 925
Gly Thr Asp Asn Ser Val Val Leu Ser Arg Lys Tyr Thr Ser Phe Pro
930 935 940
Trp Leu Leu Gly Cys Ala Ala Asn Trp Ile Leu Arg Gly Thr Ser Phe
945 950 955 960
Val Tyr Val Pro Ser Ala Leu Asn Pro Ala Ala Asp Pro Ser Ala Gly
965 970 975
Arg Leu Gly Leu Tyr Arg Pro Leu Leu His Leu Pro Phe Arg Pro Thr
980 985 990
Thr Gly Arg Thr Ser Leu Tyr Ala Val Ser Pro Ser Val Pro Ser His
995 1000 1005
Leu Pro Asp Arg Val His Phe Ala Ser Pro Leu His Val Ala Trp
1010 1015 1020
Arg Pro Pro Lys Ser Pro Asn Ser Asn Asn Pro Asp Trp Asp Phe
1025 1030 1035
Asn Pro Asn Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala
1040 1045 1050
Gly Ala Phe Gly Pro Gly Phe Thr Pro Pro His Gly Gly Leu Leu
1055 1060 1065
Gly Trp Ser Pro Gln Ala Gln Gly Ile Leu Thr Thr Val Pro Ala
1070 1075 1080
Ala Pro Pro Pro Ala Ser Thr Asn Arg Gln Ser Gly Arg Gln Pro
1085 1090 1095
Thr Pro Ile Ser Pro Pro Leu Arg Asp Ser His Pro Gln Ala Met
1100 1105 1110
Gln Trp Asn Ser Thr Thr Phe His Gln Ala Leu Leu Asp Pro Arg
1115 1120 1125
Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser Ser Gly Thr
1130 1135 1140
Val Asn Pro Val Pro Thr Thr Ala Ser Pro Ile Ser Ser Ile Phe
1145 1150 1155
Ser Arg Thr Gly Asp Pro Ala Pro Asn Gly Ser Lys Gly Lys Arg
1160 1165 1170
Lys Arg Arg Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu
1175 1180 1185
Lys Leu Ala Gly Asp Val Glu Ser Asn Pro Gly Pro Met Asp Ala
1190 1195 1200
Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly Ala Val
1205 1210 1215
Phe Val Ser Pro Ser Gln Glu Ile His Ala Arg Phe Arg Arg Met
1220 1225 1230
Gly Gly Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn Leu
1235 1240 1245
Ser Val Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu Asp
1250 1255 1260
Pro Ala Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn
1265 1270 1275
Pro Asn Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Leu Glu
1280 1285 1290
Gly Gly Ser Gly Gly Met Glu Asn Thr Thr Ser Gly Phe Leu Gly
1295 1300 1305
Pro Leu Leu Val Leu Gln Ala Gly Phe Phe Leu Leu Thr Arg Ile
1310 1315 1320
Leu Thr Ile Pro Gln Ser Leu Asp Ser Trp Trp Thr Ser Leu Asn
1325 1330 1335
Phe Leu Gly Gly Ala Pro Thr Cys Pro Gly Gln Asn Ser Gln Ser
1340 1345 1350
Pro Thr Ser Asn His Ser Pro Thr Ser Cys Pro Pro Ile Cys Pro
1355 1360 1365
Gly Tyr Arg Trp Met Cys Leu Arg Arg Phe Ile Ile Phe Leu Phe
1370 1375 1380
Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu Val Leu Leu Asp Tyr
1385 1390 1395
Gln Gly Met Leu Pro Val Cys Pro Leu Leu Pro Gly Thr Ser Thr
1400 1405 1410
Thr Ser Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala Gln Gly
1415 1420 1425
Thr Ser Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser Asp Gly
1430 1435 1440
Asn Cys Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe Ala Arg
1445 1450 1455
Phe Leu Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu
1460 1465 1470
Leu Val Pro Phe Val Gln Trp Phe Val Gly Leu Ser Pro Thr Val
1475 1480 1485
Trp Leu Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro Ser Leu
1490 1495 1500
Tyr Asn Ile Leu Ser Pro Phe Leu Pro Leu Leu Pro Ile Phe Phe
1505 1510 1515
Cys Leu Trp Val Tyr Ile
1520
<210> 26
<211> 1571
<212> PRT
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 26
Met Ser Leu Leu Trp Gly Gly Val Thr Val Leu Ala Ala Met Leu Ile
1 5 10 15
Ala Gly Gln Val Ala Ser Val Val Phe Leu Val Ser Lys Ser Gly Pro
20 25 30
Pro Ser Gly Lys Ser Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro
35 40 45
Asn Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala Gly Ala Phe
50 55 60
Gly Pro Gly Phe Thr Pro Pro His Gly Gly Leu Leu Gly Trp Ser Pro
65 70 75 80
Gln Ala Gln Gly Ile Leu Thr Thr Val Pro Ala Ala Pro Pro Pro Ala
85 90 95
Ser Thr Asn Arg Gln Ser Gly Arg Gln Pro Thr Pro Ile Ser Pro Pro
100 105 110
Leu Arg Asp Ser His Pro Gln Ala Met Gln Trp Asn Ser Thr Thr Phe
115 120 125
His Gln Ala Leu Leu Asp Pro Arg Val Arg Gly Leu Tyr Phe Pro Ala
130 135 140
Gly Gly Ser Ser Ser Gly Thr Val Asn Pro Val Pro Thr Thr Ala Ser
145 150 155 160
Pro Ile Ser Ser Ile Phe Ser Arg Thr Gly Asp Pro Ala Pro Asn Gly
165 170 175
Ser Lys Ser Gly Ser Lys Met Pro Leu Ser Tyr Gln His Phe Arg Lys
180 185 190
Leu Leu Leu Leu Asp Asp Glu Ala Gly Pro Leu Glu Glu Glu Leu Pro
195 200 205
Arg Leu Ala Asp Glu Gly Leu Asn Arg Arg Val Ala Glu Asp Leu Asn
210 215 220
Leu Gly Asn Leu Asn Val Ser Ile Pro Trp Thr His Lys Val Gly Asn
225 230 235 240
Phe Thr Gly Leu Ala Ser Ser Thr Val Pro Val Phe Asn Pro Glu Trp
245 250 255
Gln Thr Pro Ser Phe Pro His Ile His Leu Gln Glu Asp Ile Ile Asn
260 265 270
Arg Cys Gln Gln Tyr Val Gly Pro Leu Thr Val Asn Glu Lys Arg Arg
275 280 285
Leu Lys Leu Ile Met Pro Ala Arg Phe Tyr Pro Asn Leu Thr Lys Tyr
290 295 300
Leu Pro Leu Asp Lys Gly Ile Lys Pro Tyr Tyr Pro Glu His Ala Val
305 310 315 320
Asn His Tyr Phe Lys Thr Arg His Tyr Leu His Thr Leu Trp Lys Ala
325 330 335
Gly Ile Leu Tyr Lys Arg Glu Thr Thr Arg Ser Ala Ser Phe Cys Gly
340 345 350
Ser Pro Tyr Ser Trp Glu Gln Glu Leu Gln His Gly Arg Leu Val Phe
355 360 365
Gln Thr Ser Thr Arg His Gly Asp Glu Ser Phe Cys Ser Gln Ser Ser
370 375 380
Gly Ile Leu Ser Arg Ser Pro Val Gly Pro Cys Val Arg Ser Gln Leu
385 390 395 400
Lys Gln Ser Arg Leu Gly Leu Gln Pro Gln Gln Gly Ser Leu Ala Arg
405 410 415
Gly Lys Ser Gly Arg Ser Gly Ser Ile Arg Ala Arg Val His Pro Thr
420 425 430
Thr Arg Arg Ser Phe Gly Val Glu Pro Ser Gly Ser Gly His Ile Asp
435 440 445
Asn Ser Ala Ser Ser Thr Ser Ser Cys Leu His Gln Ser Ala Val Arg
450 455 460
Lys Thr Ala Tyr Ser His Leu Ser Thr Ser Lys Arg Gln Ser Ser Ser
465 470 475 480
Gly His Ala Val Glu Leu His Asn Ile Pro Pro Ser Ser Ala Arg Ser
485 490 495
Gln Ser Glu Gly Pro Ile Phe Ser Ala Trp Trp Leu Gln Phe Arg Asn
500 505 510
Ser Lys Pro Ala Ser Asp Tyr Ala Leu Thr His Ile Val Asn Leu Leu
515 520 525
Glu Asp Trp Gly Pro Ala Thr Glu His Gly Glu His Asn Ile Arg Ile
530 535 540
Pro Arg Thr Pro Ala Arg Val Thr Gly Gly Val Phe Leu Val Asp Lys
545 550 555 560
Asn Pro His Asn Thr Thr Glu Ser Arg Leu Val Val Asp Phe Ser Gln
565 570 575
Phe Ser Arg Gly Ser Thr His Val Ser Trp Pro Lys Phe Ala Val Pro
580 585 590
Asn Leu Gln Ser Leu Thr Asn Leu Leu Ser Ser Asn Leu Ser Trp Leu
595 600 605
Ser Leu Asp Val Ser Ala Ala Phe Tyr His Ile Pro Leu His Pro Ala
610 615 620
Ala Met Pro His Leu Leu Val Gly Ser Ser Gly Leu Pro Arg Tyr Val
625 630 635 640
Ala Arg Leu Ser Ser Thr Ser Arg Asn Ile Asn Tyr Gln His Gly Thr
645 650 655
Met Gln Asp Leu His Asp Ser Cys Ser Arg Asn Leu Tyr Val Ser Leu
660 665 670
Leu Leu Leu Tyr Lys Thr Phe Gly Arg Lys Leu His Leu Tyr Ser His
675 680 685
Pro Ile Ile Leu Gly Phe Arg Lys Ile Pro Met Gly Val Gly Leu Ser
690 695 700
Pro Phe Leu Leu Ala Gln Phe Thr Ser Ala Ile Cys Ser Val Val Arg
705 710 715 720
Arg Ala Phe Pro His Cys Leu Ala Phe Ser Tyr Met Asp Asp Val Val
725 730 735
Leu Gly Ala Lys Ser Val Gln His Leu Glu Ser Leu Phe Thr Ser Ile
740 745 750
Thr Asn Phe Leu Leu Ser Leu Gly Ile His Leu Asn Pro Asn Lys Thr
755 760 765
Lys Arg Trp Gly Tyr Ser Leu Asn Phe Met Gly Tyr Val Ile Gly Ser
770 775 780
Trp Gly Thr Leu Pro Gln Glu His Ile Val Leu Lys Ile Lys Gln Cys
785 790 795 800
Phe Arg Lys Leu Pro Val Asn Arg Pro Ile Asp Trp Lys Val Cys Gln
805 810 815
Arg Ile Val Gly Leu Leu Gly Phe Ala Ala Pro Phe Thr Gln Cys Gly
820 825 830
Tyr Pro Ala Leu Met Pro Leu Tyr Ala Cys Ile Gln Ser Lys Gln Ala
835 840 845
Phe Thr Phe Ser Pro Thr Tyr Lys Ala Phe Leu Cys Lys Gln Tyr Leu
850 855 860
Asn Leu Tyr Pro Val Ala Arg Gln Arg Ser Gly Leu Cys Gln Val Phe
865 870 875 880
Ala Asp Ala Thr Pro Thr Gly Trp Gly Leu Ala Ile Gly His Arg Ala
885 890 895
Met Arg Gly Thr Phe Val Ala Pro Leu Pro Ile His Thr Ala Glu Leu
900 905 910
Leu Ala Ala Cys Phe Ala Arg Ser Arg Ser Gly Ala Lys Leu Ile Gly
915 920 925
Thr Asp Asn Ser Val Val Leu Ser Arg Lys Tyr Thr Ser Phe Pro Trp
930 935 940
Leu Leu Gly Cys Ala Ala Asn Trp Ile Leu Arg Gly Thr Ser Phe Val
945 950 955 960
Tyr Val Pro Ser Ala Leu Asn Pro Ala Ala Asp Pro Ser Ala Gly Arg
965 970 975
Leu Gly Leu Tyr Arg Pro Leu Leu His Leu Pro Phe Arg Pro Thr Thr
980 985 990
Gly Arg Thr Ser Leu Tyr Ala Val Ser Pro Ser Val Pro Ser His Leu
995 1000 1005
Pro Asp Arg Val His Phe Ala Ser Pro Leu His Val Ala Trp Arg
1010 1015 1020
Pro Pro Ser Lys Ser Pro Gly Ser Gly Pro Pro Met Gln Leu Phe
1025 1030 1035
His Leu Cys Leu Ile Ile Ser Cys Ser Cys Pro Thr Val Gln Ala
1040 1045 1050
Ser Lys Leu Cys Leu Gly Trp Leu Trp Gly Met Asp Ile Asp Pro
1055 1060 1065
Tyr Lys Glu Phe Gly Ala Ser Val Glu Leu Leu Ser Phe Leu Pro
1070 1075 1080
Ser Asp Phe Phe Pro Ser Ile Arg Asp Leu Leu Asp Thr Ala Ser
1085 1090 1095
Ala Leu Tyr Arg Glu Ala Leu Glu Ser Pro Glu His Cys Ser Pro
1100 1105 1110
His His Thr Ala Leu Arg Gln Ala Ile Leu Cys Trp Gly Glu Leu
1115 1120 1125
Met Asn Leu Ala Thr Trp Val Gly Ser Asn Leu Glu Asp Pro Ala
1130 1135 1140
Ser Arg Glu Leu Val Val Ser Tyr Val Asn Val Asn Met Gly Leu
1145 1150 1155
Lys Ile Arg Gln Leu Leu Trp Phe His Ile Ser Cys Leu Thr Phe
1160 1165 1170
Gly Arg Glu Thr Val Leu Glu Tyr Leu Val Ser Phe Gly Val Trp
1175 1180 1185
Ile Arg Thr Pro Pro Ala Tyr Arg Pro Pro Asn Ala Pro Ile Leu
1190 1195 1200
Ser Thr Leu Pro Glu Thr Thr Val Val Arg Arg Arg Gly Arg Ser
1205 1210 1215
Pro Arg Arg Arg Thr Pro Ser Pro Arg Arg Arg Arg Ser Gln Ser
1220 1225 1230
Pro Arg Arg Arg Arg Ser Gln Ser Arg Glu Ser Gln Cys Met Asp
1235 1240 1245
Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly Ala
1250 1255 1260
Val Phe Val Ser Pro Ser Gln Glu Ile His Ala Arg Phe Arg Arg
1265 1270 1275
Met Gly Gly Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn
1280 1285 1290
Leu Ser Val Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu
1295 1300 1305
Asp Pro Ala Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe
1310 1315 1320
Asn Pro Asn Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala
1325 1330 1335
Ser Lys Gly Gly Lys Ser Gly Met Glu Asn Thr Thr Ser Gly Phe
1340 1345 1350
Leu Gly Pro Leu Leu Val Leu Gln Ala Gly Phe Phe Leu Leu Thr
1355 1360 1365
Arg Ile Leu Thr Ile Pro Gln Ser Leu Asp Ser Trp Trp Thr Ser
1370 1375 1380
Leu Asn Phe Leu Gly Gly Ala Pro Thr Cys Pro Gly Gln Asn Ser
1385 1390 1395
Gln Ser Pro Thr Ser Asn His Ser Pro Thr Ser Cys Pro Pro Ile
1400 1405 1410
Cys Pro Gly Tyr Arg Trp Met Cys Leu Arg Arg Phe Ile Ile Phe
1415 1420 1425
Leu Phe Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu Val Leu Leu
1430 1435 1440
Asp Tyr Gln Gly Met Leu Pro Val Cys Pro Leu Leu Pro Gly Thr
1445 1450 1455
Ser Thr Thr Ser Thr Gly Pro Cys Lys Thr Cys Thr Ile Pro Ala
1460 1465 1470
Gln Gly Thr Ser Met Phe Pro Ser Cys Cys Cys Thr Lys Pro Ser
1475 1480 1485
Asp Gly Asn Cys Thr Cys Ile Pro Ile Pro Ser Ser Trp Ala Phe
1490 1495 1500
Ala Arg Phe Leu Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu
1505 1510 1515
Ser Leu Leu Val Pro Phe Val Gln Trp Phe Val Gly Leu Ser Pro
1520 1525 1530
Thr Val Trp Leu Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro
1535 1540 1545
Ser Leu Tyr Asn Ile Leu Ser Pro Phe Leu Pro Leu Leu Pro Ile
1550 1555 1560
Phe Phe Cys Leu Trp Val Tyr Ile
1565 1570
<210> 27
<211> 7239
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 27
gtaatctatt cgatataccg ttgctaacag tatactggcc caataactgt ggatggaaaa 60
tctataataa tacattaata tcatccgatg gtgctagggt tatttggatg gatgcgtata 120
aattttcttg cggtttatct ttacaagact attgttatca ttggggtagc aaaccagaga 180
gccgaccatt cgatttaata aaaaaatcag atgctaaacg caattctaaa tcgttggtca 240
aagaatctat ggcatccttg aaatccttgt acgaggcatt cgagacacaa tcaggagcgt 300
tagaagtttt aatgagtcca tgtaggatgt tttcgttttc tagaatagaa gacatgttct 360
taactagtgt cattaataga gtatccgaga atactggaat ggggatgtat tatcctacca 420
acgatatacc ttctctattt atcgaatcat ctatctgtct agattatatt atagtaaata 480
atcaggaatc caacaaatat cgtatcaaat ctgttctcga tatcatttct tcaaaacaat 540
accctgcagg acgtcccaac tacgttaaaa atggtacaaa aggaaagtta tatatcgcgt 600
tgtgtaaagt taccgtacct actaacgacc atattccagt agtttatcac gatgatgaca 660
atactaccac ctttattaca gtattgacgt ccgtcgatat tgaaactgct atcagagcag 720
gatattcgat agtcgaatta ggggctttac aatgggataa taatattcca gaacttaaaa 780
acggtttact ggatagtatc aagatgattt atgacttgaa cgcagttaca acaaataatt 840
tattggaaca gctcatagaa aatattaact ttaacaactc tagtataatt tcgttgtttt 900
atacatttgc cattagttat tgccgagcat tcatttactc aattatggaa accatagatc 960
cggtgtatat atctcagttc agttataaag aattatacgt tagtagctct tataaagata 1020
ttaatgaatc catgagtcag atggtaaaat tataaaaagt gaaaaacaat attattttta 1080
tcgttggttg ttacactatg tctctgctgt ggggcggagt gacagtgctg gccgctatgc 1140
tgattgctgg acaggtggcc agcgtggtgt tcctggtgtc taagtctgga cctcctagcg 1200
gcaagagcaa cagcaacaac cccgactggg acttcaaccc caacaaggac cattggccag 1260
aggccaatca agtcggagcc ggcgcttttg gccctggctt tacacctcct catggcggac 1320
tgcttggatg gtcacctcag gctcagggca tcctgacaac agtgcctgct gctccacctc 1380
ctgccagcac caatagacag tctggcagac agcccacacc tatcagccct ccactgagag 1440
acagccatcc tcaggccatg cagtggaaca gcaccacctt tcatcaggcc ctgctggacc 1500
ctagagtgcg gggcctttat tttcctgccg gcggatctag cagcggcacc gtgaatcctg 1560
tgcctacaac cgcctctcct atcagcagca tcttcagcag aaccggcgat cccgctccta 1620
acggcagcaa gtctggctcc aagatgcccc tgagctacca gcacttcaga aaactgctgc 1680
tgctggacga cgaggccgga cctctggaag aagaactgcc tagactggcc gacgagggcc 1740
tgaatagaag agtggccgag gacctgaacc tgggcaacct gaatgtgtct atcccctgga 1800
cacacaaagt gggcaacttc acaggcctgg ccagctctac cgtgcctgtg ttcaatcccg 1860
agtggcagac ccctagcttc cctcacatcc atctgcaaga ggacatcatc aaccggtgcc 1920
agcagtacgt gggccctctg accgtgaacg agaagcggag actgaagctg atcatgcccg 1980
ccagattcta ccccaacctg accaagtacc tgcctctgga caagggcatc aagccttact 2040
accctgagca cgccgtgaac cactacttca agacccggca ctacctgcac accctgtgga 2100
aggccggcat cctgtataag agagagacaa ccagaagcgc cagcttctgc ggcagccctt 2160
actcttggga gcaagagctg cagcacggca gactggtgtt ccagacctct acaagacacg 2220
gcgacgagtc tttctgcagc cagagcagcg gaatcctgag cagatctcct gtgggacctt 2280
gtgtgcggag ccagctgaaa cagagtagac tgggcctgca gcctcagcag ggatctctgg 2340
ctagaggaaa gagcggcaga agcggcagca tcagagccag agtgcaccct accaccagaa 2400
gaagctttgg cgtcgagcct agcggctccg gccacatcga taatagcgcc agcagcacca 2460
gcagctgcct gcatcagtcc gccgttagaa agaccgccta cagccacctg agcacctcca 2520
agagacagag cagctctgga cacgccgtgg aactgcacaa catccctcca agcagcgcca 2580
gatctcagag cgagggccct atcttttctg cctggtggct gcagttcaga aacagcaagc 2640
ccgccagcga ctacgccctg acacacatcg tgaacctgct ggaagattgg ggccctgcca 2700
cagaacacgg cgagcacaat atcagaatcc ccagaacacc cgccagagtg acaggcggag 2760
tgtttctggt ggacaagaac cctcacaaca ccaccgagag caggctggtg gtggacttca 2820
gccagtttag cagaggcagc acccacgtgt cctggcctaa attcgccgtg cctaacctgc 2880
agagcctgac caatctgctg agcagcaacc tgagctggct gagcctggat gtgtccgccg 2940
ccttctatca catcccactg catcctgccg ccatgcctca tctgcttgtg ggaagttctg 3000
gcctgcctag atacgtggcc aggctgtcct ctaccagccg gaacatcaat taccagcacg 3060
ggaccatgca ggacctgcac gacagctgta gccggaacct gtacgttagc ctgctcctgc 3120
tgtacaagac cttcggcaga aagctgcacc tgtactctca ccccatcatc ctgggcttca 3180
gaaagatccc catgggcgtg ggcctgtctc catttctgct ggcccagttt accagcgcca 3240
tctgctctgt tgtgcggaga gcctttcctc actgcctggc cttcagctac atggacgatg 3300
tggtgctggg cgccaagtct gtgcagcacc tggaaagcct gtttacctcc atcaccaact 3360
ttctgctgtc cctgggaatc catctgaacc ctaacaagac caagagatgg ggctacagcc 3420
tgaacttcat gggctacgtg atcggcagct ggggcacact gcctcaagag cacatcgtgc 3480
tgaaaatcaa gcagtgcttt cggaagctgc ccgtgaacag acccatcgac tggaaagtgt 3540
gccagcggat cgttggcctg ctgggatttg ccgctccttt cacacagtgc ggctaccccg 3600
ctctcatgcc tctgtatgcc tgtatccaga gcaagcaggc cttcacattc agccctacct 3660
acaaggcctt cctgtgcaag cagtacctga atctgtaccc cgtggccaga cagagaagcg 3720
gcctgtgtca agtgttcgcc gatgccacac ctacaggatg gggactcgcc attggacaca 3780
gggccatgag aggaaccttt gtggcccctc tgcctatcca cacagccgaa ttgctggctg 3840
cctgcttcgc cagaagtaga tccggcgcca agctgatcgg caccgacaat tctgtggtcc 3900
tgagccggaa gtacaccagc tttccatggc tgctgggctg tgccgccaac tggattctga 3960
gaggcaccag cttcgtgtac gtgcccagcg ctcttaaccc tgccgctgat ccttctgctg 4020
ggagactcgg cctgtacaga cctctgctgc atctgccctt cagacccacc acaggcagaa 4080
ccagcctgta tgccgtgtct cctagcgtgc caagccatct gcctgatcgg gtgcactttg 4140
cctctccact tcatgtggct tggcggccac ctagcaagag ccctggatct ggaccaccta 4200
tgcagctgtt tcacctgtgc ctgatcatct cttgcagctg ccctacagtg caggccagca 4260
agctgtgtct cggatggctc tggggcatgg acatcgaccc ctacaaagaa ttcggcgcca 4320
gcgtcgagct gctgagcttc ctgcctagcg acttcttccc ctccatccgg gatctgctgg 4380
atactgctag cgccctgtat cgcgaggccc tggaatctcc tgagcactgt tctccacacc 4440
acactgccct gagacaggct atcctgtgtt ggggcgagct gatgaacctg gccacatggg 4500
tcggaagcaa cctggaagat cccgccagca gagaactggt ggtgtcctac gtgaacgtga 4560
acatgggcct gaagatcaga cagctgctgt ggttccacat ctcctgcctg acctttggcc 4620
gggaaaccgt gctggaatac ctggtgtcct ttggcgtgtg gatcagaacc cctccagcct 4680
accgacctcc taacgctcct atcctgtcta ccctgcctga gacaacagtc gtgcggcgga 4740
gaggaagaag ccctagaaga aggaccccat ctcctcggcg gagaagatca cagtcccctc 4800
ggagaagaag atcccagagc cgggaatccc agtgctgatt tttgttcgac attaaaaatt 4860
gaaaataaat acaaaggttc ttgagggttg tgttaaattg aaagcgagaa ataatcataa 4920
atatgattca ggtgacggat ccatggacgc tatgaagagg ggcctgtgct gtgtgctgct 4980
gctgtgcgga gctgtgtttg tgtcccctag ccaagagatc cacgccagat tcagaagaat 5040
gggcggctgg tccagcaagc ccagacaagg catgggcacc aatctgagcg tgcccaatcc 5100
tctgggattc ttcccagacc accagctgga tcctgccttc ggcgccaaca gcaacaaccc 5160
cgactgggac ttcaacccca acaaggacca ttggccagag gccaatcaag tgggcgctag 5220
caaaggcggc aagagcggca tggagaatac cacctctggc tttctgggcc ctctgctggt 5280
tctgcaggcc ggcttctttc tgctgacccg gatcctgaca atccctcaga gcctggatag 5340
ctggtggaca agcctgaact tccttggcgg cgctcctaca tgccctggcc agaattctca 5400
gagccccacc agcaatcaca gccccacaag ctgccctcca atctgccctg gctacagatg 5460
gatgtgcctg cggcggttca tcatctttct gttcatcctg ctgctctgcc tgatcttcct 5520
gctggtgctc ctggactatc agggcatgct gcctgtgtgt cctctgctgc ctggcaccag 5580
cacaacatct acaggccctt gcaagacctg cacaatccca gctcagggca cctccatgtt 5640
tcccagctgc tgttgcacca agcctagcga cggcaactgc acatgcatcc ccattccttc 5700
cagctgggcc ttcgccagat ttctgtggga atgggccagc gtgcggttca gctggctgtc 5760
tctgcttgtg cctttcgtgc agtggttcgt gggcctgtct cctacagtgt ggctgagcgt 5820
gatctggatg atgtggtact ggggccctag cctgtacaat attctgagcc ccttcctgcc 5880
tctgctccca atcttcttct gcctgtgggt gtacatctga ttaaccgagt ttctgcatta 5940
ttgtaattcg tatgctggca ccatcaaaga atcacttcta aaagatatca atatcacaca 6000
tacaaatatt actaccctat tgaatgagac agccaaggtt atcaagttag taaaatctct 6060
ggtagataaa gaagatactg atattgtgaa taatttcatt accaaagaaa ttaaaaacag 6120
agacaaaata gttaatagtt tgtctctatc aaacctggac tttcgtttgt aaattggggc 6180
tttttgtaca ataaatgggt gttgccaatg attcatcccc tgaatatcaa tggatgtctc 6240
cccatagatt atcagatact gttatattag gagactgttt gtattttaac aatataatgt 6300
cccaattaga tttacaccaa aattgggctc catcagttag attgttaaat tattttaaga 6360
attttaataa ggaaacacta ctaaagatag aagagaatga ttacattaat tcatcctttt 6420
tccaacaaaa ggataaacga ttttatccta taaacgacga tttttatcac atatctacag 6480
gaggatatgg tatagtcttt aagatagata actatgtagt aaaatttgta ttcgaggcca 6540
caaaattata tagtcccatg gaaactacgg cggagttcac agtacccaaa tttctataca 6600
acaatctaaa gggagatgaa aaaaaattaa tcgtgtgtgc gtgggccatg ggattaaact 6660
ataaattaac atttttacat actctgtata aacgtgttct tcatatgttg ctattattga 6720
tacaaactat ggatggtcag gaactatcat tgagatattc ttctaaagtt tttttaaagg 6780
cgtttaacga gagaaaggac agtatcaaat tcgtgaaatt actatcccac ttttatccgg 6840
cagttattaa cagtaatatt aatgttataa actattttaa ccgcatgttt cactttttcg 6900
aacatgaaaa gagaactaac tacgaatacg aaagaggaaa tattataatt tttcccctag 6960
cactgtattc ggcagataaa gtagataccg agctagctat caaattagga tttaaatctt 7020
tggtacaata cataaagttt atctttttac agatggctct gttatacatt aaaatttacg 7080
aactaccatg ctgcgacaac tttttacacg cagatcttaa acccgataat atcttacttt 7140
ttgattccaa tgaaccaata ataattcatc taaaggataa aaagtttgtt tttaatgaac 7200
gtattaaatc ggcattaaac gactttgact tttcccaag 7239
<210> 28
<211> 97
<212> DNA
<213> 人工序列
<220>
<223> 启动子
<400> 28
tcgacattaa aaattgaaaa taaatacaaa ggttcttgag ggttgtgtta aattgaaagc 60
gagaaataat cataaatatg attcaggtga cggatcc 97
<210> 29
<211> 96
<212> DNA
<213> 人工序列
<220>
<223> TPA序列
<400> 29
atggacgcta tgaagagggg cctgtgctgt gtgctgctgc tgtgcggagc tgtgtttgtg 60
tcccctagcc aagagatcca cgccagattc agaaga 96
<210> 30
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> TPA肽
<400> 30
Met Asp Ala Met Lys Arg Gly Leu Cys Cys Val Leu Leu Leu Cys Gly
1 5 10 15
Ala Val Phe Val Ser Pro Ser Gln Glu Ile His Ala Arg Phe Arg Arg
20 25 30
<210> 31
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 31
Ser Lys Ser Gly Pro Pro Ser Gly Lys Ser
1 5 10
<210> 32
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 32
Gly Ser Lys Ser Gly Ser Lys
1 5
<210> 33
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 33
Ser Lys Ser Pro Gly Ser Gly Pro Pro
1 5
<210> 34
<211> 8
<212> PRT
<213> 人工序列
<220>
<223> 接头肽
<400> 34
Ala Ser Lys Gly Gly Lys Ser Gly
1 5
<210> 35
<211> 1097
<212> DNA
<213> 人工序列
<220>
<223> F11左侧翼
<400> 35
gtaatctatt cgatataccg ttgctaacag tatactggcc caataactgt ggatggaaaa 60
tctataataa tacattaata tcatccgatg gtgctagggt tatttggatg gatgcgtata 120
aattttcttg cggtttatct ttacaagact attgttatca ttggggtagc aaaccagaga 180
gccgaccatt cgatttaata aaaaaatcag atgctaaacg caattctaaa tcgttggtca 240
aagaatctat ggcatccttg aaatccttgt acgaggcatt cgagacacaa tcaggagcgt 300
tagaagtttt aatgagtcca tgtaggatgt tttcgttttc tagaatagaa gacatgttct 360
taactagtgt cattaataga gtatccgaga atactggaat ggggatgtat tatcctacca 420
acgatatacc ttctctattt atcgaatcat ctatctgtct agattatatt atagtaaata 480
atcaggaatc caacaaatat cgtatcaaat ctgttctcga tatcatttct tcaaaacaat 540
accctgcagg acgtcccaac tacgttaaaa atggtacaaa aggaaagtta tatatcgcgt 600
tgtgtaaagt taccgtacct actaacgacc atattccagt agtttatcac gatgatgaca 660
atactaccac ctttattaca gtattgacgt ccgtcgatat tgaaactgct atcagagcag 720
gatattcgat agtcgaatta ggggctttac aatgggataa taatattcca gaacttaaaa 780
acggtttact ggatagtatc aagatgattt atgacttgaa cgcagttaca acaaataatt 840
tattggaaca gctcatagaa aatattaact ttaacaactc tagtataatt tcgttgtttt 900
atacatttgc cattagttat tgccgagcat tcatttactc aattatggaa accatagatc 960
cggtgtatat atctcagttc agttataaag aattatacgt tagtagctct tataaagata 1020
ttaatgaatc catgagtcag atggtaaaat tataaaaagt gaaaaacaat attattttta 1080
tcgttggttg ttacact 1097
<210> 36
<211> 1319
<212> DNA
<213> 人工序列
<220>
<223> F11右侧翼
<400> 36
ttaaccgagt ttctgcatta ttgtaattcg tatgctggca ccatcaaaga atcacttcta 60
aaagatatca atatcacaca tacaaatatt actaccctat tgaatgagac agccaaggtt 120
atcaagttag taaaatctct ggtagataaa gaagatactg atattgtgaa taatttcatt 180
accaaagaaa ttaaaaacag agacaaaata gttaatagtt tgtctctatc aaacctggac 240
tttcgtttgt aaattggggc tttttgtaca ataaatgggt gttgccaatg attcatcccc 300
tgaatatcaa tggatgtctc cccatagatt atcagatact gttatattag gagactgttt 360
gtattttaac aatataatgt cccaattaga tttacaccaa aattgggctc catcagttag 420
attgttaaat tattttaaga attttaataa ggaaacacta ctaaagatag aagagaatga 480
ttacattaat tcatcctttt tccaacaaaa ggataaacga ttttatccta taaacgacga 540
tttttatcac atatctacag gaggatatgg tatagtcttt aagatagata actatgtagt 600
aaaatttgta ttcgaggcca caaaattata tagtcccatg gaaactacgg cggagttcac 660
agtacccaaa tttctataca acaatctaaa gggagatgaa aaaaaattaa tcgtgtgtgc 720
gtgggccatg ggattaaact ataaattaac atttttacat actctgtata aacgtgttct 780
tcatatgttg ctattattga tacaaactat ggatggtcag gaactatcat tgagatattc 840
ttctaaagtt tttttaaagg cgtttaacga gagaaaggac agtatcaaat tcgtgaaatt 900
actatcccac ttttatccgg cagttattaa cagtaatatt aatgttataa actattttaa 960
ccgcatgttt cactttttcg aacatgaaaa gagaactaac tacgaatacg aaagaggaaa 1020
tattataatt tttcccctag cactgtattc ggcagataaa gtagataccg agctagctat 1080
caaattagga tttaaatctt tggtacaata cataaagttt atctttttac agatggctct 1140
gttatacatt aaaatttacg aactaccatg ctgcgacaac tttttacacg cagatcttaa 1200
acccgataat atcttacttt ttgattccaa tgaaccaata ataattcatc taaaggataa 1260
aaagtttgtt tttaatgaac gtattaaatc ggcattaaac gactttgact tttcccaag 1319
<210> 37
<211> 3741
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 37
atgtctctgc tgtggggcgg agtgacagtg ctggccgcta tgctgattgc tggacaggtg 60
gccagcgtgg tgttcctggt gtctaagtct ggacctccta gcggcaagag caacagcaac 120
aaccccgact gggacttcaa ccccaacaag gaccattggc cagaggccaa tcaagtcgga 180
gccggcgctt ttggccctgg ctttacacct cctcatggcg gactgcttgg atggtcacct 240
caggctcagg gcatcctgac aacagtgcct gctgctccac ctcctgccag caccaataga 300
cagtctggca gacagcccac acctatcagc cctccactga gagacagcca tcctcaggcc 360
atgcagtgga acagcaccac ctttcatcag gccctgctgg accctagagt gcggggcctt 420
tattttcctg ccggcggatc tagcagcggc accgtgaatc ctgtgcctac aaccgcctct 480
cctatcagca gcatcttcag cagaaccggc gatcccgctc ctaacggcag caagtctggc 540
tccaagatgc ccctgagcta ccagcacttc agaaaactgc tgctgctgga cgacgaggcc 600
ggacctctgg aagaagaact gcctagactg gccgacgagg gcctgaatag aagagtggcc 660
gaggacctga acctgggcaa cctgaatgtg tctatcccct ggacacacaa agtgggcaac 720
ttcacaggcc tggccagctc taccgtgcct gtgttcaatc ccgagtggca gacccctagc 780
ttccctcaca tccatctgca agaggacatc atcaaccggt gccagcagta cgtgggccct 840
ctgaccgtga acgagaagcg gagactgaag ctgatcatgc ccgccagatt ctaccccaac 900
ctgaccaagt acctgcctct ggacaagggc atcaagcctt actaccctga gcacgccgtg 960
aaccactact tcaagacccg gcactacctg cacaccctgt ggaaggccgg catcctgtat 1020
aagagagaga caaccagaag cgccagcttc tgcggcagcc cttactcttg ggagcaagag 1080
ctgcagcacg gcagactggt gttccagacc tctacaagac acggcgacga gtctttctgc 1140
agccagagca gcggaatcct gagcagatct cctgtgggac cttgtgtgcg gagccagctg 1200
aaacagagta gactgggcct gcagcctcag cagggatctc tggctagagg aaagagcggc 1260
agaagcggca gcatcagagc cagagtgcac cctaccacca gaagaagctt tggcgtcgag 1320
cctagcggct ccggccacat cgataatagc gccagcagca ccagcagctg cctgcatcag 1380
tccgccgtta gaaagaccgc ctacagccac ctgagcacct ccaagagaca gagcagctct 1440
ggacacgccg tggaactgca caacatccct ccaagcagcg ccagatctca gagcgagggc 1500
cctatctttt ctgcctggtg gctgcagttc agaaacagca agcccgccag cgactacgcc 1560
ctgacacaca tcgtgaacct gctggaagat tggggccctg ccacagaaca cggcgagcac 1620
aatatcagaa tccccagaac acccgccaga gtgacaggcg gagtgtttct ggtggacaag 1680
aaccctcaca acaccaccga gagcaggctg gtggtggact tcagccagtt tagcagaggc 1740
agcacccacg tgtcctggcc taaattcgcc gtgcctaacc tgcagagcct gaccaatctg 1800
ctgagcagca acctgagctg gctgagcctg gatgtgtccg ccgccttcta tcacatccca 1860
ctgcatcctg ccgccatgcc tcatctgctt gtgggaagtt ctggcctgcc tagatacgtg 1920
gccaggctgt cctctaccag ccggaacatc aattaccagc acgggaccat gcaggacctg 1980
cacgacagct gtagccggaa cctgtacgtt agcctgctcc tgctgtacaa gaccttcggc 2040
agaaagctgc acctgtactc tcaccccatc atcctgggct tcagaaagat ccccatgggc 2100
gtgggcctgt ctccatttct gctggcccag tttaccagcg ccatctgctc tgttgtgcgg 2160
agagcctttc ctcactgcct ggccttcagc tacatggacg atgtggtgct gggcgccaag 2220
tctgtgcagc acctggaaag cctgtttacc tccatcacca actttctgct gtccctggga 2280
atccatctga accctaacaa gaccaagaga tggggctaca gcctgaactt catgggctac 2340
gtgatcggca gctggggcac actgcctcaa gagcacatcg tgctgaaaat caagcagtgc 2400
tttcggaagc tgcccgtgaa cagacccatc gactggaaag tgtgccagcg gatcgttggc 2460
ctgctgggat ttgccgctcc tttcacacag tgcggctacc ccgctctcat gcctctgtat 2520
gcctgtatcc agagcaagca ggccttcaca ttcagcccta cctacaaggc cttcctgtgc 2580
aagcagtacc tgaatctgta ccccgtggcc agacagagaa gcggcctgtg tcaagtgttc 2640
gccgatgcca cacctacagg atggggactc gccattggac acagggccat gagaggaacc 2700
tttgtggccc ctctgcctat ccacacagcc gaattgctgg ctgcctgctt cgccagaagt 2760
agatccggcg ccaagctgat cggcaccgac aattctgtgg tcctgagccg gaagtacacc 2820
agctttccat ggctgctggg ctgtgccgcc aactggattc tgagaggcac cagcttcgtg 2880
tacgtgccca gcgctcttaa ccctgccgct gatccttctg ctgggagact cggcctgtac 2940
agacctctgc tgcatctgcc cttcagaccc accacaggca gaaccagcct gtatgccgtg 3000
tctcctagcg tgccaagcca tctgcctgat cgggtgcact ttgcctctcc acttcatgtg 3060
gcttggcggc cacctagcaa gagccctgga tctggaccac ctatgcagct gtttcacctg 3120
tgcctgatca tctcttgcag ctgccctaca gtgcaggcca gcaagctgtg tctcggatgg 3180
ctctggggca tggacatcga cccctacaaa gaattcggcg ccagcgtcga gctgctgagc 3240
ttcctgccta gcgacttctt cccctccatc cgggatctgc tggatactgc tagcgccctg 3300
tatcgcgagg ccctggaatc tcctgagcac tgttctccac accacactgc cctgagacag 3360
gctatcctgt gttggggcga gctgatgaac ctggccacat gggtcggaag caacctggaa 3420
gatcccgcca gcagagaact ggtggtgtcc tacgtgaacg tgaacatggg cctgaagatc 3480
agacagctgc tgtggttcca catctcctgc ctgacctttg gccgggaaac cgtgctggaa 3540
tacctggtgt cctttggcgt gtggatcaga acccctccag cctaccgacc tcctaacgct 3600
cctatcctgt ctaccctgcc tgagacaaca gtcgtgcggc ggagaggaag aagccctaga 3660
agaaggaccc catctcctcg gcggagaaga tcacagtccc ctcggagaag aagatcccag 3720
agccgggaat cccagtgctg a 3741
<210> 38
<211> 882
<212> DNA
<213> 乙型肝炎病毒
<400> 38
atgggaggct ggtccagcaa acccagacaa ggcatgggca ccaatctgag cgtgcccaat 60
cctctgggat tcttcccaga ccaccagctg gatcctgcct tcggcgccaa cagcaacaac 120
cccgactggg acttcaaccc caacaaggac cattggccag aggccaatca agtgggcgct 180
agcaaaggcg gcaagagcgg catggagaat accacctctg gctttctggg ccctctgctg 240
gttctgcagg ccggcttctt tctgctgacc cggatcctga caatccctca gagcctggat 300
agctggtgga caagcctgaa cttccttggc ggcgctccta catgccctgg ccagaattct 360
cagagcccca ccagcaatca cagccccaca agctgccctc caatctgccc tggctacaga 420
tggatgtgcc tgcggcggtt catcatcttt ctgttcatcc tgctgctgtg cctgatcttc 480
ctgctggtgc tgctggacta tcagggcatg ctgcctgtgt gtcctctgct gcctggcacc 540
agcacaacat ctacaggccc ttgcaagacc tgcacaatcc cagctcaggg cacctccatg 600
tttcccagct gctgttgcac caagcctagc gacggcaact gcacatgcat ccccattcct 660
tccagctggg ccttcgccag atttctgtgg gaatgggcca gcgtgcggtt cagctggctg 720
tctctgcttg tgcctttcgt gcagtggttc gtgggcctgt ctcctacagt gtggctgagc 780
gtgatctgga tgatgtggta ctggggccct agcctgtaca atattctgag ccccttcctg 840
cctctgctcc caatcttctt ctgcctgtgg gtgtacatct ga 882
<210> 39
<211> 12012
<212> DNA
<213> 人工序列
<220>
<223> 载体
<400> 39
ccaccgcctc ggacctggcc gacctcatct tccccgagcg cctcaggctg acgctgcgca 60
acggcctgcc cgactttatg agccaaagca tgttgcaaaa actttcggta aaaaatgtaa 120
ttactccctc ctgcacaggc agcaaagccc ccgctccctc cagaaacaca tacaaagcct 180
cagcgtccat agcttaccga gcacggcagg cgcaagagtc agagaaaagg ctgagctcta 240
acctgactgc ccgctcctgt gctcaatata taagccctaa cctacactga cgtaaaaggg 300
cccaaaagtc taaaaaaata acccgcccaa aatgacacac acgcccagca cacgcccaga 360
aaccggtgac acactcaaaa aaatacgtgc gcttcctcaa acgcccaaac cggcgtcatt 420
tccgggttcc cacgctacgt caccgctcag cgactttcaa attccgtcga ccgttaaaaa 480
cgtcactcgc cccgccccta acggtcgccc ttctctcggc caatcacctt cctcccttcc 540
caaattcaaa cgcctcattt gcatattaac gcgcacaaaa agtttgaggt atatatttga 600
atgatggttt aaacgcggcc gccaggccta cccactagtc aattcgggag gatcgaaacg 660
gcagatcgca aaaaacagta catacagaag gagacatgaa catgaacatc aaaaaaattg 720
taaaacaagc cacagttctg acttttacga ctgcacttct ggcaggagga gcgactcaag 780
ccttcgcgaa agaaaataac caaaaagcat acaaagaaac gtacggcgtc tctcatatta 840
cacgccatga tatgctgcag atccctaaac agcagcaaaa cgaaaaatac caagtgcctc 900
aattcgatca atcaacgatt aaaaatattg agtctgcaaa aggacttgat gtgtgggaca 960
gctggccgct gcaaaacgct gacggaacag tagctgaata caacggctat cacgttgtgt 1020
ttgctcttgc gggaagcccg aaagacgctg atgacacatc aatctacatg ttttatcaaa 1080
aggtcggcga caactcaatc gacagctgga aaaacgcggg ccgtgtcttt aaagacagcg 1140
ataagttcga cgccaacgat ccgatcctga aagatcagac gcaagaatgg tccggttctg 1200
caacctttac atctgacgga aaaatccgtt tattctacac tgactattcc ggtaaacatt 1260
acggcaaaca aagcctgaca acagcgcagg taaatgtgtc aaaatctgat gacacactca 1320
aaatcaacgg agtggaagat cacaaaacga tttttgacgg agacggaaaa acatatcaga 1380
acgttcagca gtttatcgat gaaggcaatt atacatccgg cgacaaccat acgctgagag 1440
accctcacta cgttgaagac aaaggccata aataccttgt attcgaagcc aacacgggaa 1500
cagaaaacgg ataccaaggc gaagaatctt tatttaacaa agcgtactac ggcggcggca 1560
cgaacttctt ccgtaaagaa agccagaagc ttcagcagag cgctaaaaaa cgcgatgctg 1620
agttagcgaa cggcgccctc ggtatcatag agttaaataa tgattacaca ttgaaaaaag 1680
taatgaagcc gctgatcact tcaaacacgg taactgatga aatcgagcgc gcgaatgttt 1740
tcaaaatgaa cggcaaatgg tacttgttca ctgattcacg cggttcaaaa atgacgatcg 1800
atggtattaa ctcaaacgat atttacatgc ttggttatgt atcaaactct ttaaccggcc 1860
cttacaagcc gctgaacaaa acagggcttg tgctgcaaat gggtcttgat ccaaacgatg 1920
tgacattcac ttactctcac ttcgcagtgc cgcaagccaa aggcaacaat gtggttatca 1980
caagctacat gacaaacaga ggcttcttcg aggataaaaa ggcaacattt gcgccaagct 2040
tcttaatgaa catcaaaggc aataaaacat ccgttgtcaa aaacagcatc ctggagcaag 2100
gacagctgac agtcaactaa taacagcaaa aagaaaatgc cgatacttca ttggcatttt 2160
cttttatttc tcaacaagat ggtgaattga ctagtgggta gatccacagg acgggtgtgg 2220
tcgccatgat cgcgtagtcg atagtggctc caagtagcga agcgagcagg actgggcggc 2280
ggccaaagcg gtcggacagt gctccgagaa cgggtgcgca tagaaattgc atcaacgcat 2340
atagcgctag cagcacgcca tagtgactgg cgatgctgtc ggaatggacg atatcccgca 2400
agaggcccgg cagtaccggc ataaccaagc ctatgcctac agcatccagg gtgacggtgc 2460
cgaggatgac gatgagcgca ttgttagatt tcatacacgg tgcctgactg cgttagcaat 2520
ttaactgtga taaactaccg cattaaagct tatcgatgat aagctgtcaa acatgagaat 2580
tgatccggaa cccttaatat aacttcgtat aatgtatgct atacgaagtt attaggtccc 2640
tcgactatag ggtcaccgtc gacagcgaca cacttgcatc ggatgcagcc cggttaacgt 2700
gccggcacgg cctgggtaac caggtatttt gtccacataa ccgtgcgcaa aatgttgtgg 2760
ataagcagga cacagcagca atccacagca ggcatacaac cgcacaccga ggttactccg 2820
ttctacaggt tacgacgaca tgtcaatact tgcccttgac aggcattgat ggaatcgtag 2880
tctcacgctg atagtctgat cgacaataca agtgggaccg tggtcccaga ccgataatca 2940
gaccgacray acgagtggga ycgtggtccc agactaataa tcagaccgac gatacgagtg 3000
ggaccgtggt cccagactaa taatcagacc gacgatacga gtgggaccgt ggtyccagwc 3060
tratwatcag accgacgata cragtggrac mgtggkccca gasakaataw tcagrccgag 3120
wtaygcwktc kggcctgtaa caaaggacat taagtaaaga cagatamrmg tgrgactaaa 3180
acgtggtccc agtctgatta tcagaccgac gatacgagtg ggaccgtggt cccagactaa 3240
taatcagacc gacgatacga gtgggaccgt ggtcccagac taataatcag accgacgata 3300
cgagtgggac cgtggtccca gtctgattat cagaccgacg atacaagtgg aacagtgggc 3360
ccagagagaa tattcaggcc agttatgctt tctggcctgt aacaaaggac attaagtaaa 3420
gacagataaa cgtagactaa aacgtggtcg catcagggtg ctggcttttc aagttcctta 3480
agaatggcct caattttctc tatacactca gttggaacac gagacctgtc caggttaagc 3540
accattttat cgcccttata caatactgtc gctccaggag caaactgatg tcgtgagctt 3600
aaactagttc ttgatgcaga tgacgtttta agcacagaag ttaaaagagt gataacttct 3660
tcagcttcaa atatcacccc agcttttttc tgctcatgaa ggttagatgc ctgctgctta 3720
agtaattcct ctttatctgt aaaggctttt tgaagtgcat cacctgaccg ggcagatagt 3780
tcaccggggt gagaaaaaag agcaacaact gatttaggca atttggcggt gttgatacag 3840
cgggtaataa tcttacgtga aatattttcc gcatcagcca gcgcagaaat atttccagca 3900
aattcattct gcaatcggct tgcataacgc tgaccacgtt cataagcact tgttgggcga 3960
taatcgttac ccaatctgga taatgcagcc atctgctcat catccagctc gccaaccaga 4020
acacgataat cactttcggt aagtgcagca gctttacgac ggcgactccc atcggcaatt 4080
tctatgacac cagatactct tcgaccgaac gccggtgtct gttgaccagt cagtagaaaa 4140
gaagggatga gatcatccag tgcgtcctca gtaagcagct cctggtcacg ttcattacct 4200
gaccataccc gagaggtctt ctcaacacta tcaccccgga gcacttcaag agtaaacttc 4260
acatcccgac cacatacagg caaagtaatg gcattaccgc gagccattac tcctacgcgc 4320
gcaattaacg aatccaccat cggggcagct ggtgtcgata acgaagtatc ttcaaccggt 4380
tgagtattga gcgtatgttt tggaataaca ggcgcacgct tcattatcta atctcccagc 4440
gtggtttaat cagacgatcg aaaatttcat tgcagacagg ttcccaaata gaaagagcat 4500
ttctccaggc accagttgaa gagcgttgat caatggcctg ttcaaaaaca gttctcatcc 4560
ggatctgacc tttaccaact tcatccgttt cacgtacaac attttttaga accatgcttc 4620
cccaggcatc ccgaatttgc tcctccatcc acggggactg agagccatta ctattgctgt 4680
atttggtaag caaaatacgt acatcaggct cgaacccttt aagatcaacg ttcttgagca 4740
gatcacgaag catatcgaaa aactgcagtg cggaggtgta gtcaaacaac tcagcaggcg 4800
tgggaacaat cagcacatca gcagcacata cgacattaat cgtgccgata cccaggttag 4860
gcgcgctgtc aataactatg acatcatagt catgagcaac agtttcaatg gccagtcgga 4920
gcatcaggtg tggatcggtg ggcagtttac cttcatcaaa tttgcccatt aactcagttt 4980
caatacggtg cagagccaga caggaaggaa taatgtcaag ccccggccag caagtgggct 5040
ttattgcata agtgacatcg tccttttccc caagatagaa aggcaggaga gtgtcttctg 5100
catgaatatg aagatctggt acccatccgt gatacattga ggctgttccc tgggggtcgt 5160
taccttccac gagcaaaaca cgtagcccct tcagagccag atcctgagca agatgaacag 5220
aaactgaggt tttgtaaacg ccacctttat gggcagcaac cccgatcacc ggtggaaata 5280
cgtcttcagc acgtcgcaat cgcgtaccaa acacatcacg catatgatta atttgttcaa 5340
ttgtataacc aacacgttgc tcaacccgtc ctcgaatttc catatccggg tgcggtagtc 5400
gccctgcttt ctcggcatct ctgatagcct gagaagaaac cccaactaaa tccgctgctt 5460
cacctattct ccagcgccgg gttattttcc tcgcttccgg gctgtcatca ttaaactgtg 5520
caatggcgat agccttcgtc atttcatgac cagcgtttat gcactggtta agtgtttcca 5580
tgagtttcat tctgaacatc ctttaatcat tgctttgcgt ttttttatta aatcttgcaa 5640
tttactgcaa agcaacaaca aaatcgcaaa gtcatcaaaa aaccgcaaag ttgtttaaaa 5700
taagagcaac actacaaaag gagataagaa gagcacatac ctcagtcact tattatcact 5760
agcgctcgcc gcagccgtgt aaccgagcat agcgagcgaa ctggcgagga agcaaagaag 5820
aactgttctg tcagatagct cttacgctca gcgcaagaag aaatatccac cgtgggaaaa 5880
actccaggta gaggtacaca cgcggatagc caattcagag taataaactg tgataatcaa 5940
ccctcatcaa tgatgacgaa ctaacccccg atatcaggtc acatgacgaa gggaaagaga 6000
aggaaatcaa ctgtgacaaa ctgccctcaa atttggcttc cttaaaaatt acagttcaaa 6060
aagtatgaga aaatccatgc aggctgaagg aaacagcaaa actgtgacaa attaccctca 6120
gtaggtcaga acaaatgtga cgaaccaccc tcaaatctgt gacagataac cctcagacta 6180
tcctgtcgtc atggaagtga tatcgcggaa ggaaaatacg atatgagtcg tctggcggcc 6240
tttctttttc tcaatgtatg agaggcgcat tggagttctg ctgttgatct cattaacaca 6300
gacctgcagg aagcggcggc ggaagtcagg catacgctgg taactttgag gcagctggta 6360
acgctctatg atccagtcga ttttcagaga gacgatgcct gagccatccg gcttacgata 6420
ctgacacagg gattcgtata aacgcatggc atacggattg gtgatttctt ttgtttcact 6480
aagccgaaac tgcgtaaacc ggttctgtaa cccgataaag aagggaatga gatatgggtt 6540
gatatgtaca ctgtaaagcc ctctggatgg actgtgcgca cgtttgataa accaaggaaa 6600
agattcatag cctttttcat cgccggcatc ctcttcaggg cgataaaaaa ccacttcctt 6660
ccccgcgaaa ctcttcaatg cctgccgtat atccttactg gcttccgcag aggtcaatcc 6720
gaatatttca gcatatttag caacatggat ctcgcagata ccgtcatgtt cctgtagggt 6780
gccatcagat tttctgatct ggtcaacgaa cagatacagc atacgttttt gatcccggga 6840
gagactatat gccgcctcag tgaggtcgtt tgactggacg attcgcgggc tatttttacg 6900
tttcttgtga ttgataaccg ctgtttccgc catgacagat ccatgtgaag tgtgacaagt 6960
ttttagattg tcacactaaa taaaaaagag tcaataagca gggataactt tgtgaaaaaa 7020
cagcttcttc tgagggcaat ttgtcacagg gttaagggca atttgtcaca gacaggactg 7080
tcatttgagg gtgatttgtc acactgaaag ggcaatttgt cacaacacct tctctagaac 7140
cagcatggat aaaggcctac aaggcgctct aaaaaagaag atctaaaaac tataaaaaaa 7200
ataattataa aaatatcccc gtggataagt ggataacccc aagggaagtt ttttcaggca 7260
tcgtgtgtaa gcagaatata taagtgctgt tccctggtgc ttcctcgctc actcgagggc 7320
ttcgccctgt cgctcaactg cggcgagcac tactggctgt aaaaggacag accacatcat 7380
ggttctgtgt tcattaggtt gttctgtcca ttgctgacat aatccgctcc acttcaacgt 7440
aacaccgcac gaagatttct attgttcctg aaggcatatt caaatcgttt tcgttaccgc 7500
ttgcaggcat catgacagaa cactacttcc tataaacgct acacaggctc ctgagattaa 7560
taatgcggat ctctacgata atgggagatt ttcccgactg tttcgttcgc ttctcagtgg 7620
ataacagcca gcttctctgt ttaacagaca aaaacagcat atccactcag ttccacattt 7680
ccatataaag gccaaggcat ttattctcag gataattgtt tcagcatcgc aaccgcatca 7740
gactccggca tcgcaaactg cacccggtgc cgggcagcca catccagcgc aaaaaccttc 7800
gtgtagactt ccgttgaact gatggactta tgtcccatca ggctttgcag aactttcagc 7860
ggtataccgg catacagcat gtgcatcgca taggaatggc ggaacgtatg tggtgtgacc 7920
ggaacagaga acgtcacacc gtcagcagca gcggcggcaa ccgcctcccc aatccaggtc 7980
ctgaccgttc tgtccgtcac ttcccagatc cgcgctttct ctgtccttcc tgtgcgacgg 8040
ttacgccgct ccatgagctt atcgcgaata aatacctgtg acggaagatc acttcgcaga 8100
ataaataaat cctggtgtcc ctgttgatac cgggaagccc tgggccaact tttggcgaaa 8160
atgagacgtt gatcggcacg taagaggttc caactttcac cataatgaaa taagatcact 8220
accgggcgta ttttttgagt tatcgagatt ttcaggagct aaggaagcta aaatggagaa 8280
aaaaatcact ggatatacca ccgttgatat atcccaatgg catcgtaaag aacattttga 8340
ggcatttcag tcagttgctc aatgtaccta taaccagacc gttcagctgg atattacggc 8400
ctttttaaag accgtaaaga aaaataagca caagttttat ccggccttta ttcacattct 8460
tgcccgcctg atgaatgctc atccggagtt ccgtatggca atgaaagacg gtgagctggt 8520
gatatgggat agtgttcacc cttgttacac cgttttccat gagcaaactg aaacgttttc 8580
atcgctctgg agtgaatacc acgacgattt ccggcagttt ctacacatat attcgcaaga 8640
tgtggcgtgt tacggtgaaa acctggccta tttccctaaa gggtttattg agaatatgtt 8700
tttcgtctca gccaatccct gggtgagttt caccagtttt gatttaaacg tggccaatat 8760
ggacaacttc ttcgcccccg ttttcaccat gggcaaatat tatacgcaag gcgacaaggt 8820
gctgatgccg ctggcgattc aggttcatca tgccgtttgt gatggcttcc atgtcggcag 8880
aatgcttaat gaattacaac agtactgcga tgagtggcag ggcggggcgt aattttttta 8940
aggcagttat tggtgccctt aaacgcctgg ttgctacgcc tgaataagtg ataataagcg 9000
gatgaatggc agaaattcga tgataagctg tcaaacatga gaattggtcg acggcgcgcc 9060
aaagcttgca tgcctgcagc cgcgtaacct ggcaaaatcg gttacggttg agtaataaat 9120
ggatgccctg cgtaagcggg gcacatttca ttacctcttt ctccgcaccc gacatagata 9180
ataacttcgt atagtataca ttatacgaag ttatctagta gacttaatcg cgtttaaacc 9240
catcatcaat aatatacctc aaactttttg tgcgcgttaa tatgcaaatg aggcgtttga 9300
atttgggaag ggaggaaggt gattggccga gagaagggcg accgttaggg gcggggcgag 9360
tgacgttttg atgacgtgac cgcgaggagg agccagtttg caagttctcg tgggaaaagt 9420
gacgtcaaac gaggtgtggt ttgaacacgg aaatactcaa ttttcccgcg ctctctgaca 9480
ggaaatgagg tgtttctagg cggatgcaag tgaaaacggg ccattttcgc gcgaaaactg 9540
aatgaggaag tgaaaatctg agtaatttcg cgtttatgac agggaggagt atttgccgag 9600
ggccgagtag actttgaccg attacgtggg ggtttcgatt accgtgtttt tcacctaaat 9660
ttccgcgtac ggtgtcaaag tccggtgttt ttacgtaggt gtcagctgat cgccagggta 9720
tttaaacctg cgctctccag tcaagaggcc actcttgagt gccagcgaga agagttttct 9780
cctccgcgcg cgagtcagat ctacactttg aaaggcgatc gctagcgaca tcgatcacaa 9840
gtttgtacaa aaaagcaggc tccaccatgg gaacccgcgt tttgagattt ctgtcgccga 9900
ctaaattcat gtcgcgcgat agtggtgttt atcgccgata gagatggcga tattggaaaa 9960
atcgatattt gaaaatatgg catattgaaa atgtcgccga tgtgagtttc tgtgtaactg 10020
atatcgccat ttttccaaaa gtgatttttg ggcatacgcg atatctggcg atagcgctta 10080
tatcgtttac gggggatggc gatagacgac tttggtgact tgggcgattc tgtgtgtcgc 10140
aaatatcgca gtttcgatat aggtgacaga cgatatgagg ctatatcgcc gatagaggcg 10200
acatcaagct ggcacatggc caatgcatat cgatctatac attgaatcaa tattggccat 10260
tagccatatt attcattggt tatatagcat aaatcaatat tggctattgg ccattgcata 10320
cgttgtatcc atatcataat atgtacattt atattggctc atgtccaaca ttaccgccat 10380
gttgacattg attattgact agttattaat agtaatcaat tacggggtca ttagttcata 10440
gcccatatat ggagttccgc gttacataac ttacggtaaa tggcccgcct ggctgaccgc 10500
ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt tcccatagta acgccaatag 10560
ggactttcca ttgacgtcaa tgggtggagt atttacggta aactgcccac ttggcagtac 10620
atcaagtgta tcatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg 10680
cctggcatta tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg 10740
tattagtcat cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat 10800
agcggtttga ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt 10860
tttggcacca aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc 10920
aaatgggcgg taggcgtgta cggtgggagg tctatataag cagagctctc cctatcagtg 10980
atagagatct ccctatcagt gatagagatc gtcgacgagc tcgtttagtg aaccgtcaga 11040
tcgcctggag acgccatcca cgctgttttg acctccatag aagacaccgg gaccgatcca 11100
gcctccgcgg ccgggaacgg tgcattggaa cgcggattcc ccgtgccaag agtgacgtaa 11160
gtaccgccta tagagtctat aggcccaccc ccttggcttc ttatgcatgc tatactgttt 11220
ttggcttggg gtctatacac ccccgcttcc tcatgttata ggtgatggta tagcttagcc 11280
tataggtgtg ggttattgac cattattgac cactccccta ttggtgacga tactttccat 11340
tactaatcca taacatggct ctttgccaca actctcttta ttggctatat gccaatacac 11400
tgtccttcag agactgacac ggactctgta tttttacagg atggggtctc atttattatt 11460
tacaaattca catatacaac accaccgtcc ccagtgcccg cagtttttat taaacataac 11520
gtgggatctc cacgcgaatc tcgggtacgt gttccggaca tgggctcttc tccggtagcg 11580
gcggagcttc tacatccgag ccctgctccc atgcctccag cgactcatgg tcgctcggca 11640
gctccttgct cctaacagtg gaggccagac ttaggcacag cacgatgccc accaccacca 11700
gtgtgccgca caaggccgtg gcggtagggt atgtgtctga aaatgagctc ggggagcggg 11760
cttgcaccgc tgacgcattt ggaagactta aggcagcggc agaagaagat gcaggcagct 11820
gagttgttgt gttctgataa gagtcagagg taactcccgt tgcggtgctg ttaacggtgg 11880
agggcagtgt agtctgagca gtactcgttg ctgccgcgcg cgccaccaga cataatagct 11940
gacagactaa cagactgttc ctttccatgg gtcttttctg cagtcaccgt ccttgacacg 12000
aagcttggta cc 12012
<210> 40
<211> 29187
<212> DNA
<213> 人工序列
<220>
<223> 载体
<400> 40
gcggccgctc gagcatgcat ctagagggcc ctattctata gtgtcaccta aatgctagag 60
ctcgctgatc agcctcgact gtgccttcta gttgccagcc atctgttgtt tgcccctccc 120
ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt cctttcctaa taaaatgagg 180
aaattgcatc gcattgtctg agtaggtgtc attctattct ggggggtggg gtggggcagg 240
acagcaaggg ggaggattgg gaagacaata gcaggcatgc tggggatgcg gtgggctcta 300
tggcttctga ggcggaaaga accagctggg gctcgagggg ggatcgatcc cgtcgagata 360
tctagaccca gctttcttgt acaaagtggt gatcgattcg acagatcgcg atcgcagtga 420
gtagtgttct ggggcggggg aggacctgca tgagggccag aatgactgaa atctgtgctt 480
ttctgtgtgt tgcagcatca tgagcggaag cggctccttt gagggagggg tattcagccc 540
ttatctgacg gggcgtctcc cctcctgggc gggagtgcgt cagaatgtga tgggatccac 600
ggtggacggc cggcccgtgc agcccgcgaa ctcttcaacc ctgacctatg caaccctgag 660
ctcttcgtcg gtggacgcag ctgccgccgc agctgctgca tccgccgcca gcgccgtgcg 720
cggaatggcc atgggcgccg gctactacgg cactctggtg gccaactcga gttccaccaa 780
taatcccgcc agcctgaacg aggagaagct gctgctgctg atggcccagc ttgaggcctt 840
gacccagcgc ctgggcgagc tgacccagca ggtggctcag ctgcaggagc agacgcgggc 900
cgcggttgcc acggtgaaat ccaaataaaa aatgaatcaa taaataaacg gagacggttg 960
ttgattttaa cacagagtct gaatctttat ttgatttttc gcgcgcggta ggccctggac 1020
caccggtctc gatcattgag cacccggtgg atcttttcca ggacccggta gaggtgggct 1080
tggatgttga ggtacatggg catgagcccg tcccgggggt ggaggtagct ccattgcagg 1140
gcctcgtgct cgggggtggt gttgtaaatc acccagtcat agcaggggcg cagggcgtgg 1200
tgttgcacaa tatctttgag gaggagactg atggccacgg gcagcccttt ggtgtaggtg 1260
tttacaaatc tgttgagctg ggagggatgc atgcgggggg agatgaggtg catcttggcc 1320
tggatcttga gattggcgat gttaccgccc agatcccgcc tggggttcat gttgtgcagg 1380
accaccagca cggtgtatcc ggtgcacttg gggaatttat catgcaactt ggaagggaag 1440
gcgtgaaaga atttggcgac gcccttgtgt ccgcccaggt tttccatgca ctcatccatg 1500
atgatggcaa tgggcccgtg ggcggcggcc tgggcaaaga cgtttcgggg gtcggacaca 1560
tcatagttgt ggtcctgggt gaggtcatca taggccattt taatgaattt ggggcggagg 1620
gtgccggact gggggacaaa ggtaccctcg atcccggggg cgtagttccc ctcacagatc 1680
tgcatctccc aggctttgag ctcagagggg gggatcatgt ccacctgcgg ggcgataaag 1740
aacacggttt ccggggcggg ggagatgagc tgggccgaaa gcaagttccg gagcagctgg 1800
gacttgccgc agccggtggg gccgtaaatg accccgatga ccggctgcag gtggtagttg 1860
agggagagac agctgccgtc ctcccggagg aggggggcca cctcgttcat catctcgcgc 1920
acgtgcatgt tctcgcgcac cagttccgcc aggaggcgct ctccccccag agataggagc 1980
tcctggagcg aggcgaagtt tttcagcggc ttgagtccgt cggccatggg cattttggag 2040
agggtctgtt gcaagagttc caagcggtcc cagagctcgg tgatgtgctc tacggcatct 2100
cgatccagca gacctcctcg tttcgcgggt tgggacgact gcgggagtag ggcaccagac 2160
gatgggcgtc cagcgcagcc agggtccggt ccttccaggg ccgcagcgtc cgcgtcaggg 2220
tggtctccgt cacggtgaag gggtgcgcgc cgggctgggc gcttgcgagg gtgcgcttca 2280
ggctcatccg gctggtcgaa aaccgctccc gatcggcgcc ctgcgcgtcg gccaggtagc 2340
aattgaccat gagttcgtag ttgagcgcct cggccgcgtg gcctttggcg cggagcttac 2400
ctttggaagt ctgcccgcag gcgggacaga ggagggactt gagggcgtag agcttggggg 2460
cgaggaagac ggaatcgggg gcgtaggcgt ccgcgccgca gtgggcgcag acggtctcgc 2520
actccacgag ccaggtgagg tcgggctggt cggggtcaaa aaccagtttc ccgccgttct 2580
ttttgatgcg tttcttacct ttggtctcca tgagctcgtg tccccgctgg gtgacaaaga 2640
ggctgtccgt gtccccgtag accgacttta tgggccggtc ctcgagcggt gtgccgcggt 2700
cctcctcgta gaggaacccc gcccactccg agacgaaagc ccgggtccag gccagcacga 2760
aggaggccac gtgggacggg tagcggtcgt tgtccaccag cgggtccact ttttccaggg 2820
tatgcaaaca catgtccccc tcgtccacat ccaggaaggt gattggcttg taagtgtagg 2880
ccacgtgacc gggggtcccg gccggggggg tataaaaggg ggcgggcccc tgctcgtcct 2940
cactgtcttc cggatcgctg tccaggagcg ccagctgttg gggtaggtat tccctctcga 3000
aggcgggcat gacctcggca ctcaggttgt cagtttctag aaacgaggag gatttgatat 3060
tgacggtgcc agcggagatg cctttcaaga gcccctcgtc catctggtca gaaaagacga 3120
tttttttgtt gtcgagcttg gtggcgaagg agccgtagag ggcgttggaa aggagcttgg 3180
cgatggagcg catggtctgg tttttttcct tgtcggcgcg ctccttggcc gcgatgttga 3240
gctgcacgta ctcgcgcgcc acgcacttcc attcggggaa gacggtggtc atctcgtcgg 3300
gcacgattct gacctgccaa cctcgattat gcagggtgat gaggtccaca ctggtggcca 3360
cctcgccgcg caggggctcg ttggtccagc agaggcggcc gcccttgcgc gagcagaagg 3420
ggggcagagg gtccagcatg acctcgtcgg gggggtcggc atcgatggtg aagatgccgg 3480
gcaggagatc ggggtcgaag tagctgatgg aagtggccag atcgtccagg gaagcttgcc 3540
attcgcgcac ggccagcgcg cgctcgtagg gactgagggg cgtgccccag ggcatggggt 3600
gggtgagcgc ggaggcgtac atgccgcaga tgtcgtagac gtagaggggc tcctcgagga 3660
tgccgatgta ggtggggtag cagcgccccc cgcggatgct ggcgcgcacg tagtcataca 3720
gctcgtgcga gggcgcgagg agccccgggc ccaggttggt gcgactgggc ttttcggcgc 3780
ggtagacgat ctggcgaaag atggcatgcg agttggagga gatggtgggc ctttggaaga 3840
tgttgaagtg ggcgtggggg aggccgaccg agtcgcggat gaagtgggcg taggagtctt 3900
gcagtttggc gacgagctcg gcggtgacga ggacgtccag agcgcagtag tcgagggtct 3960
cctggatgat gtcatacttg agctggccct tttgtttcca cagctcgcgg ttgagaagga 4020
actcttcgcg gtccttccag tactcttcga gggggaaccc gtcctgatct gcacggtaag 4080
agcctagcat gtagaactgg ttgacggcct tgtaggcgca gcagcccttc tccacgggga 4140
gggcgtaggc ctgggcggcc ttgcgcaggg aggtgtgcgt gagggcgaag gtgtccctga 4200
ccatgacctt gaggaactgg tgcttgaaat cgatatcgtc gcagcccccc tgctcccaga 4260
gctggaagtc cgtgcgcttc ttgtaggcgg ggttgggcaa agcgaaagta acatcgttga 4320
aaaggatctt gcccgcgcgg ggcataaagt tgcgagtgat gcggaaaggc tggggcacct 4380
cggcccggtt gttgatgacc tgggcggcga gcacgatctc gtcgaaaccg ttgatgttgt 4440
ggcccacgat gtagagttcc acgaatcgcg ggcggccctt gacgtggggc agcttcttga 4500
gctcctcgta ggtgagctcg tcggggtcgc tgagaccgtg ctgctcgagc gcccagtcgg 4560
cgagatgggg gttggcgcgg aggaaggaag tccagagatc cacggccagg gcggtttgca 4620
gacggtcccg gtactgacgg aactgctgcc cgacggccat tttttcgggg gtgacgcagt 4680
agaaggtgcg ggggtccccg tgccagcggt cccatttgag ctggagggcg agatcgaggg 4740
cgagctcgac gaggcggtcg tcccctgaga gtttcatgac cagcatgaag gggacgagct 4800
gcttgccgaa ggaccccatc caggtgtagg tttccacatc gtaggtgagg aagagccttt 4860
cggtgcgagg atgcgagccg atggggaaga actggatctc ctgccaccaa ttggaggaat 4920
ggctgttgat gtgatggaag tagaaatgcc gacggcgcgc cgaacactcg tgcttgtgtt 4980
tatacaagcg gccacagtgc tcgcaacgct gcacgggatg cacgtgctgc acgagctgta 5040
cctgagttcc tttgacgagg aatttcagtg ggaagtggag tcgtggcgcc tgcatctcgt 5100
gctgtactac gtcgtggtgg tcggcctggc cctcttctgc ctcgatggtg gtcatgctga 5160
cgagcccgcg cgggaggcag gtccagacct cggcgcgagc gggtcggaga gcgaggacga 5220
gggcgcgcag gccggagctg tccagggtcc tgagacgctg cggagtcagg tcagtgggca 5280
gcggcggcgc gcggttgact tgcaggagtt tttccagggc gcgcgggagg tccagatggt 5340
acttgatctc caccgcgccg ttggtggcga cgtcgatggc ttgcagggtc ccgtgcccct 5400
ggggtgtgac caccgtcccc cgtttcttct tgggcggctg gggcgacggg ggcggtgcct 5460
cttccatggt tagaagcggc ggcgaggacg cgcgccgggc ggcagaggcg gctcggggcc 5520
cggaggcagg ggcggcaggg gcacgtcggc gccgcgcgcg ggtaggttct ggtactgcgc 5580
ccggagaaga ctggcgtgag cgacgacgcg acggttgacg tcctggatct gacgcctctg 5640
ggtgaaggcc acgggacccg tgagtttgaa cctgaaagag agttcgacag aatcaatctc 5700
ggtatcgttg acggcggcct gccgcaggat ctcttgcacg tcgcccgagt tgtcctggta 5760
ggcgatctcg gtcatgaact gctcgatctc ctcctcctga aggtctccgc gaccggcgcg 5820
ctccacggtg gccgcgaggt cgttggagat gcggcccatg agctgcgaga aggcgttcat 5880
gcccgcctcg ttccagacgc ggctgtagac cacgacgccc tcgggatcgc gggcgcgcat 5940
gaccacctgg gcgaggttga gctccacgtg gcgcgtgaag accgcgtagt tgcagaggcg 6000
ctggtagagg tagttgagcg tggtggcgat gtgctcggtg acgaagaaat acatgatcca 6060
gcggcggagc ggcatctcgc tgacgtcgcc cagcgcctcc aagcgttcca tggcctcgta 6120
aaagtccacg gcgaagttga aaaactggga gttgcgcgcc gagacggtca actcctcctc 6180
cagaagacgg atgagctcgg cgatggtggc gcgcacctcg cgctcgaagg cccccgggag 6240
ttcctccact tcctcctctt cttcctcctc cactaacatc tcttctactt cctcctcagg 6300
cggtggtggt ggcgggggag ggggcctgcg tcgccggcgg cgcacgggca gacggtcgat 6360
gaagcgctcg atggtctcgc cgcgccggcg tcgcatggtc tcggtgacgg cgcgcccgtc 6420
ctcgcggggc cgcagcgtga agacgccgcc gcgcatctcc aggtggccgg gggggtcccc 6480
gttgggcagg gagagggcgc tgacgatgca tcttatcaat tgccccgtag ggactccgcg 6540
caaggacctg agcgtctcga gatccacggg atctgaaaac cgttgaacga aggcttcgag 6600
ccagtcgcag tcgcaaggta ggctgagcac ggtttcttct gccgggtcat gttggggagc 6660
ggggcgggcg atgctgctgg tgatgaagtt gaaataggcg gttctgagac ggcggatggt 6720
ggcgaggagc accaggtctt tgggcccggc ttgctggatg cgcagacggt cggccatgcc 6780
ccaggcgtgg tcctgacacc tggccaggtc cttgtagtag tcctgcatga gccgctccac 6840
gggcacctcc tcctcgcccg cgcggccgtg catgcgcgtg agcccgaagc cgcgctgggg 6900
ctggacgagc gccaggtcgg cgacgacgcg ctcggcgagg atggcctgct ggatctgggt 6960
gagggtggtc tggaagtcgt caaagtcgac gaagcggtgg taggctccgg tgttgatggt 7020
gtaggagcag ttggccatga cggaccagtt gacggtctgg tggcccggac gcacgagctc 7080
gtggtacttg aggcgcgagt aggcgcgcgt gtcgaagatg tagtcgttgc aggtgcgcac 7140
caggtactgg tagccgatga ggaagtgcgg cggcggctgg cggtagagcg gccatcgctc 7200
ggtggcgggg gcgccgggcg cgaggtcctc gagcatggtg cggtggtagc cgtagatgta 7260
cctggacatc caggtgatgc cggcggcggt ggtggaggcg cgcgggaact cgcggacgcg 7320
gttccagatg ttgcgcagcg gcaggaagta gttcatggtg ggcacggtct ggcccgtgag 7380
gcgcgcgcag tcgtggatgc tctatacggg caaaaacgaa agcggtcagc ggctcgactc 7440
cgtggcctgg aggctaagcg aacgggttgg gctgcgcgtg taccccggtt cgaatctcga 7500
atcaggctgg agccgcagct aacgtggtac tggcactccc gtctcgaccc aagcctgcac 7560
caaccctcca ggatacggag gcgggtcgtt ttgcaacttt ttttggaggc cggaaatgaa 7620
actagtaagc gcggaaagcg gccgaccgcg atggctcgct gccgtagtct ggagaagaat 7680
cgccagggtt gcgttgcggt gtgccccggt tcgaggccgg ccggattccg cggctaacga 7740
gggcgtggct gccccgtcgt ttccaagacc ccatagccag ccgacttctc cagttacgga 7800
gcgagcccct cttttgtttt gtttgttttt gccagatgca tcccgtactg cggcagatgc 7860
gcccccacca ccctccaccg caacaacagc cccctcctcc acagccggcg cttctgcccc 7920
cgccccagca gcagcagcaa cttccagcca cgaccgccgc ggccgccgtg agcggggctg 7980
gacagacttc tcagtatgat cacctggcct tggaagaggg cgaggggctg gcgcgcctgg 8040
gggcgtcgtc gccggagcgg cacccgcgcg tgcagatgaa aagggacgct cgcgaggcct 8100
acgtgcccaa gcagaacctg ttcagagaca ggagcggcga ggagcccgag gagatgcgcg 8160
cggcccggtt ccacgcgggg cgggagctgc ggcgcggcct ggaccgaaag agggtgctga 8220
gggacgagga tttcgaggcg gacgagctga cggggatcag ccccgcgcgc gcgcacgtgg 8280
ccgcggccaa cctggtcacg gcgtacgagc agaccgtgaa ggaggagagc aacttccaaa 8340
aatccttcaa caaccacgtg cgcaccctga tcgcgcgcga ggaggtgacc ctgggcctga 8400
tgcacctgtg ggacctgctg gaggccatcg tgcagaaccc caccagcaag ccgctgacgg 8460
cgcagctgtt cctggtggtg cagcatagtc gggacaacga ggcgttcagg gaggcgctgc 8520
tgaatatcac cgagcccgag ggccgctggc tcctggacct ggtgaacatt ctgcagagca 8580
tcgtggtgca ggagcgcggg ctgccgctgt ccgagaagct ggcggccatc aacttctcgg 8640
tgctgagtct gggcaagtac tacgctagga agatctacaa gaccccgtac gtgcccatag 8700
acaaggaggt gaagatcgac gggttttaca tgcgcatgac cctgaaagtg ctgaccctga 8760
gcgacgatct gggggtgtac cgcaacgaca ggatgcaccg cgcggtgagc gccagcaggc 8820
ggcgcgagct gagcgaccag gagctgatgc acagcctgca gcgggccctg accggggccg 8880
ggaccgaggg ggagagctac tttgacatgg gcgcggacct gcactggcag cccagccgcc 8940
gggccttgga ggcggcaggc ggtcccccct acatagaaga ggtggacgat gaggtggacg 9000
aggagggcga gtacctggaa gactgatggc gcgaccgtat ttttgctaga tgcaacaaca 9060
gccacctcct gatcccgcga tgcgggcggc gctgcagagc cagccgtccg gcattaactc 9120
ctcggacgat tggacccagg ccatgcaacg catcatggcg ctgacgaccc gcaaccccga 9180
agcctttaga cagcagcccc aggccaaccg gctctcggcc atcctggagg ccgtggtgcc 9240
ctcgcgctcc aaccccacgc acgagaaggt cctggccatc gtgaacgcgc tggtggagaa 9300
caaggccatc cgcggcgacg aggccggcct ggtgtacaac gcgctgctgg agcgcgtggc 9360
ccgctacaac agcaccaacg tgcagaccaa cctggaccgc atggtgaccg acgtgcgcga 9420
ggccgtggcc cagcgcgagc ggttccaccg cgagtccaac ctgggatcca tggtggcgct 9480
gaacgccttc ctcagcaccc agcccgccaa cgtgccccgg ggccaggagg actacaccaa 9540
cttcatcagc gccctgcgcc tgatggtgac cgaggtgccc cagagcgagg tgtaccagtc 9600
cgggccggac tacttcttcc agaccagtcg ccagggcttg cagaccgtga acctgagcca 9660
ggcgttcaag aacttgcagg gcctgtgggg cgtgcaggcc ccggtcgggg accgcgcgac 9720
ggtgtcgagc ctgctgacgc cgaactcgcg cctgctgctg ctgctggtgg cccccttcac 9780
ggacagcggc agcatcaacc gcaactcgta cctgggctac ctgattaacc tgtaccgcga 9840
ggccatcggc caggcgcacg tggacgagca gacctaccag gagatcaccc acgtgagccg 9900
cgccctgggc caggacgacc cgggcaatct ggaagccacc ctgaactttt tgctgaccaa 9960
ccggtcgcag aagatcccgc cccagtacac gctcagcgcc gaggaggagc gcatcctgcg 10020
atacgtgcag cagagcgtgg gcctgttcct gatgcaggag ggggccaccc ccagcgccgc 10080
gctcgacatg accgcgcgca acatggagcc cagcatgtac gccagcaacc gcccgttcat 10140
caataaactg atggactact tgcatcgggc ggccgccatg aactctgact atttcaccaa 10200
cgccatcctg aatccccact ggctcccgcc gccggggttc tacacgggcg agtacgacat 10260
gcccgacccc aatgacgggt tcctgtggga cgatgtggac agcagcgtgt tctccccccg 10320
accgggtgct aacgagcgcc ccttgtggaa gaaggaaggc agcgaccgac gcccgtcctc 10380
ggcgctgtcc ggccgcgagg gtgctgccgc ggcggtgccc gaggccgcca gtcctttccc 10440
gagcttgccc ttctcgctga acagtattcg cagcagcgag ctgggcagga tcacgcgccc 10500
gcgcttgctg ggcgaggagg agtacttgaa tgactcgctg ttgagacccg agcgggagaa 10560
gaacttcccc aataacggga tagagagcct ggtggacaag atgagccgct ggaagacgta 10620
tgcgcaggag cacagggacg atccgtcgca gggggccacg agccggggca gcgccgcccg 10680
taaacgccgg tggcacgaca ggcagcgggg actgatgtgg gacgatgagg attccgccga 10740
cgacagcagc gtgttggact tgggtgggag tggtaacccg ttcgctcacc tgcgcccccg 10800
catcgggcgc atgatgtaag agaaaccgaa aataaatgat actcaccaag gccatggcga 10860
ccagcgtgcg ttcgtttctt ctctgttgtt gtatctagta tgatgaggcg tgcgtacccg 10920
gagggtcctc ctccctcgta cgagagcgtg atgcagcagg cgatggcggc ggcggcggcg 10980
atgcagcccc cgctggaggc tccttacgtg cccccgcggt acctggcgcc tacggagggg 11040
cggaacagca ttcgttactc ggagctggca cccttgtacg ataccacccg gttgtacctg 11100
gtggacaaca agtcggcgga catcgcctcg ctgaactacc agaacgacca cagcaacttc 11160
ctgaccaccg tggtgcagaa caatgacttc acccccacgg aggccagcac ccagaccatc 11220
aactttgacg agcgctcgcg gtggggcggt cagctgaaaa ccatcatgca caccaacatg 11280
cccaacgtga acgagttcat gtacagcaac aagttcaagg cgcgggtgat ggtctcccgc 11340
aagaccccca acggggtgac agtgacagat ggtagtcagg atatcttgga gtatgaatgg 11400
gtggagtttg agctgcccga aggcaacttc tcggtgacca tgaccatcga cctgatgaac 11460
aacgccatca tcgacaatta cttggcggtg gggcggcaga acggggtcct ggagagcgat 11520
atcggcgtga agttcgacac taggaacttc aggctgggct gggaccccgt gaccgagctg 11580
gtcatgcccg gggtgtacac caacgaggcc ttccaccccg atattgtctt gctgcccggc 11640
tgcggggtgg acttcaccga gagccgcctc agcaacctgc tgggcattcg caagaggcag 11700
cccttccagg agggcttcca gatcatgtac gaggatctgg aggggggcaa catccccgcg 11760
ctcctggatg tcgacgccta tgagaaaagc aaggaggaga gcgccgccgc ggcgactgca 11820
gctgtagcca ccgcctctac cgaggtcagg ggcgataatt ttgccagccc tgcagcagtg 11880
gcagcggccg aggcggctga aaccgaaagt aagatagtca ttcagccggt ggagaaggat 11940
agcaaggaca ggagctacaa cgtgctgccg gacaagataa acaccgccta ccgcagctgg 12000
tacctggcct acaactatgg cgaccccgag aagggcgtgc gctcctggac gctgctcacc 12060
acctcggacg tcacctgcgg cgtggagcaa gtctactggt cgctgcccga catgatgcaa 12120
gacccggtca ccttccgctc cacgcgtcaa gttagcaact acccggtggt gggcgccgag 12180
ctcctgcccg tctactccaa gagcttcttc aacgagcagg ccgtctactc gcagcagctg 12240
cgcgccttca cctcgctcac gcacgtcttc aaccgcttcc ccgagaacca gatcctcgtc 12300
cgcccgcccg cgcccaccat taccaccgtc agtgaaaacg ttcctgctct cacagatcac 12360
gggaccctgc cgctgcgcag cagtatccgg ggagtccagc gcgtgaccgt tactgacgcc 12420
agacgccgca cctgccccta cgtctacaag gccctgggca tagtcgcgcc gcgcgtcctc 12480
tcgagccgca ccttctaaaa aatgtccatt ctcatctcgc ccagtaataa caccggttgg 12540
ggcctgcgcg cgcccagcaa gatgtacgga ggcgctcgcc aacgctccac gcaacacccc 12600
gtgcgcgtgc gcgggcactt ccgcgctccc tggggcgccc tcaagggccg cgtgcggtcg 12660
cgcaccaccg tcgacgacgt gatcgaccag gtggtggccg acgcgcgcaa ctacaccccc 12720
gccgccgcgc ccgtctccac cgtggacgcc gtcatcgaca gcgtggtggc cgacgcgcgc 12780
cggtacgccc gcgccaagag ccggcggcgg cgcatcgccc ggcggcaccg gagcaccccc 12840
gccatgcgcg cggcgcgagc cttgctgcgc agggccaggc gcacgggacg cagggccatg 12900
ctcagggcgg ccagacgcgc ggcttcaggc gccagcgccg gcaggacccg gagacgcgcg 12960
gccacggcgg cggcagcggc catcgccagc atgtcccgcc cgcggcgagg gaacgtgtac 13020
tgggtgcgcg acgccgccac cggtgtgcgc gtgcccgtgc gcacccgccc ccctcgcact 13080
tgaagatgtt cacttcgcga tgttgatgtg tcccagcggc gaggaggatg tccaagcgca 13140
aattcaagga agagatgctc caggtcatcg cgcctgagat ctacggcccc gcggtggtga 13200
aggaggaaag aaagccccgc aaaatcaagc gggtcaaaaa ggacaaaaag gaagaagatg 13260
acgatctggt ggagtttgtg cgcgagttcg ccccccggcg gcgcgtgcag tggcgcgggc 13320
ggaaagtgca cccggtgctg agacccggca ccaccgtggt cttcacgccc ggcgagcgct 13380
ccggcagcgc ttccaagcgc tcctacgacg aggtgtacgg ggacgaggac atcctcgagc 13440
aggcggccga gcgcctgggc gagtttgctt acggcaagcg cagccgcccc gccctgaagg 13500
aagaggcggt gtccatcccg ctggaccacg gcaaccccac gccgagcctc aagcccgtga 13560
ccctgcagca ggtgctgccg agcgcagcgc cgcgccgggg gttcaagcgc gagggcgagg 13620
atctgtaccc caccatgcag ctgatggtgc ccaagcgcca gaagctggaa gacgtgctgg 13680
agaccatgaa ggtggacccg gacgtgcagc ccgaggtcaa ggtgcggccc atcaagcagg 13740
tggccccggg cctgggcgtg cagaccgtgg acatcaagat ccccacggag cccatggaaa 13800
cgcagaccga gcccatgatc aagcccagca ccagcaccat ggaggtgcag acggatccct 13860
ggatgccatc ggctcctagc cgaagacccc ggcgcaagta cggcgcggcc agcctgctga 13920
tgcccaacta cgcgctgcat ccttccatca tccccacgcc gggctaccgc ggcacgcgct 13980
tctaccgcgg tcatacaacc agccgccgcc gcaagaccac cacccgccgc cgccgtcgcc 14040
gcacagccgc tgcatctacc cctgccgccc tggtgcggag agtgtaccgc cgcggccgcg 14100
cgcctctgac cctaccgcgc gcgcgctacc acccgagcat cgccatttaa actttcgcct 14160
gctttgcaga tggccctcac atgccgcctc cgcgttccca ttacgggcta ccgaggaaga 14220
aaaccgcgcc gtagaaggct ggcggggaac gggatgcgtc gccaccacca tcggcggcgg 14280
cgcgccatca gcaagcggtt ggggggaggc ttcctgcccg cgctgatccc catcatcgcc 14340
gcggcgatcg gggcgatccc cggcattgct tccgtggcgg tgcaggcctc tcagcgccac 14400
tgagacactt ggaaaacatc ttgtaataaa ccaatggact ctgacgctcc tggtcctgtg 14460
atgtgttttc gtagacagat ggaagacatc aatttttcgt ccctggctcc gcgacacggc 14520
acgcggccgt tcatgggcac ctggagcgac atcggcacca gccaactgaa cgggggcgcc 14580
ttcaattgga gcagtctctg gagcgggctt aagaatttcg ggtccacgct taaaacctat 14640
ggcagcaagg cgtggaacag caccacaggg caggcgctga gggataagct gaaagagcag 14700
aacttccagc agaaggtggt cgatgggctc gcctcgggca tcaacggggt ggtggacctg 14760
gccaaccagg ccgtgcagcg gcagatcaac agccgcctgg acccggtgcc gcccgccggc 14820
tccgtggaga tgccgcaggt ggaggaggag ctgcctcccc tggacaagcg gggcgagaag 14880
cgaccccgcc ccgacgcgga ggagacgctg ctgacgcaca cggacgagcc gcccccgtac 14940
gaggaggcgg tgaaactggg tctgcccacc acgcggccca tcgcgcccct ggccaccggg 15000
gtgctgaaac ccgaaagtaa taagcccgcg accctggact tgcctcctcc cgcttcccgc 15060
ccctctacag tggctaagcc cctgccgccg gtggccgtgg cccgcgcgcg acccgggggc 15120
tccgcccgcc ctcatgcgaa ctggcagagc actctgaaca gcatcgtggg tctgggagtg 15180
cagagtgtga agcgccgccg ctgctattaa acctaccgta gcgcttaact tgcttgtctg 15240
tgtgtgtatg tattatgtcg ccgctgtccg ccagaaggag gagtgaagag gcgcgtcgcc 15300
gagttgcaag atggccaccc catcgatgct gccccagtgg gcgtacatgc acatcgccgg 15360
acaggacgct tcggagtacc tgagtccggg tctggtgcag ttcgcccgcg ccacagacac 15420
ctacttcagt ctggggaaca agtttaggaa ccccacggtg gcgcccacgc acgatgtgac 15480
caccgaccgc agccagcggc tgacgctgcg cttcgtgccc gtggaccgcg aggacaacac 15540
ctactcgtac aaagtgcgct acacgctggc cgtgggcgac aaccgcgtgc tggacatggc 15600
cagcacctac tttgacatcc gcggcgtgct ggatcggggc cctagcttca aaccctactc 15660
cggcaccgcc tacaacagcc tggctcccaa gggagcgccc aattccagcc agtgggagca 15720
aaaaaaggca ggcaatggtg acactatgga aacacacaca tttggtgtgg ccccaatggg 15780
cggtgagaat attacaatcg acggattaca aattggaact gacgctacag ctgatcagga 15840
taaaccaatt tatgctgaca aaacattcca gcctgaacct caagtaggag aagaaaattg 15900
gcaagaaact gaaagctttt atggcggtag ggctcttaaa aaagacacaa gcatgaaacc 15960
ttgctatggc tcctatgcta gacccaccaa tgtaaaggga ggtcaagcta aacttaaagt 16020
tggagctgat ggagttccta ccaaagaatt tgacatagac ctggctttct ttgatactcc 16080
cggtggcaca gtgaatggac aagatgagta taaagcagac attgtcatgt ataccgaaaa 16140
cacgtatctg gaaactccag acacgcatgt ggtatacaaa ccaggcaagg atgatgcaag 16200
ttctgaaatt aacctggttc agcagtccat gcccaataga cccaactata ttgggttcag 16260
agacaacttt attgggctca tgtattacaa cagtactggc aatatggggg tgctggctgg 16320
tcaggcctca cagctgaatg ctgtggtcga cttgcaagac agaaacaccg agctgtcata 16380
ccagctcttg cttgactctt tgggtgacag aacccggtat ttcagtatgt ggaatcaggc 16440
ggtggacagt tatgatcctg atgtgcgcat tattgaaaac catggtgtgg aagacgaact 16500
tcccaactat tgcttccccc tggatgggtc tggcactaat gccgcttacc aaggtgtgaa 16560
agtaaaaaat ggtaacgatg gtgatgttga gagcgaatgg gaaaatgatg atactgtcgc 16620
agctcgaaat caattatgca agggcaacat ttttgccatg gaaattaacc tccaagccaa 16680
cctgtggaga agtttcctct actcgaacgt ggccctgtac ctgcccgact cttacaagta 16740
cacgccagcc aacatcaccc tgcccaccaa caccaacact tatgattaca tgaacgggag 16800
agtggtgcct ccctcgctgg tggacgccta catcaacatc ggggcgcgct ggtcgctgga 16860
ccccatggac aacgtcaatc ccttcaacca ccaccgcaac gcgggcctgc gctaccgctc 16920
catgctcctg ggcaacgggc gctacgtgcc cttccacatc caggtgcccc agaaattttt 16980
cgccatcaag agcctcctgc tcctgcccgg gtcctacacc tacgagtgga acttccgcaa 17040
ggacgtcaac atgatcctgc agagctccct cggcaacgac ctgcgcacgg acggggcctc 17100
catctccttc accagcatca acctctacgc caccttcttc cccatggcgc acaacacggc 17160
ctccacgctc gaggccatgc tgcgcaacga caccaacgac cagtccttca acgactacct 17220
ctcggcggcc aacatgctct accccatccc ggccaacgcc accaacgtgc ccatctccat 17280
cccctcgcgc aactgggccg ccttccgcgg ctggtccttc acgcgcctca agaccaagga 17340
gacgccctcg ctgggctccg ggttcgaccc ctacttcgtc tactcgggct ccatccccta 17400
cctcgacggc accttctacc tcaaccacac cttcaagaag gtctccatca ccttcgactc 17460
ctccgtcagc tggcccggca acgaccggct cctgacgccc aacgagttcg aaatcaagcg 17520
caccgtcgac ggcgagggat acaacgtggc ccagtgcaac atgaccaagg actggttcct 17580
ggtccagatg ctggcccact acaacatcgg ctaccagggc ttctacgtgc ccgagggcta 17640
caaggaccgc atgtactcct tcttccgcaa cttccagccc atgagccgcc aggtggtgga 17700
cgaggtcaac tacaaggact accaggccgt caccctggcc taccagcaca acaactcggg 17760
cttcgtcggc tacctcgcgc ccaccatgcg ccagggccag ccctaccccg ccaactaccc 17820
gtacccgctc atcggcaaga gcgccgtcac cagcgtcacc cagaaaaagt tcctctgcga 17880
cagggtcatg tggcgcatcc ccttctccag caacttcatg tccatgggcg cgctcaccga 17940
cctcggccag aacatgctct atgccaactc cgcccacgcg ctagacatga atttcgaagt 18000
cgaccccatg gatgagtcca cccttctcta tgttgtcttc gaagtcttcg acgtcgtccg 18060
agtgcaccag ccccaccgcg gcgtcatcga ggccgtctac ctgcgcaccc ccttctcggc 18120
cggtaacgcc accacctaaa ttgctacttg catgatggct gagcccacag gctccggcga 18180
gcaggagctc agggccatca tccgcgacct gggctgcggg ccctacttcc tgggcacctt 18240
cgataagcgc ttcccgggat tcatggcccc gcacaagctg gcctgcgcca tcgtcaacac 18300
ggccggccgc gagaccgggg gcgagcactg gctggccttc gcctggaacc cgcgctcgaa 18360
cacctgctac ctcttcgacc ccttcgggtt ctcggacgag cgcctcaagc agatctacca 18420
gttcgagtac gagggcctgc tgcgccgtag cgccctggcc accgaggacc gctgcgtcac 18480
cctggaaaag tccacccaga ccgtgcaggg tccgcgctcg gccgcctgcg ggctcttctg 18540
ctgcatgttc ctgcacgcct tcgtgcactg gcccgaccgc cccatggaca agaaccccac 18600
catgaacttg ctgacggggg tgcccaacgg catgctccag tcgccccagg tggaacccac 18660
cctgcgccgc aaccaggagg cgctctaccg cttcctcaac tcccactccg cctactttcg 18720
ctcccaccgc gcgcgcatcg agaaggccac cgccttcgac cgcatgaaca atcaagacat 18780
gtaaaccgtg tgtgtatgtt taaaatatct tttaataaac agcactttaa tgttacacat 18840
gcatctgaga tgattttatt ttagaaatcg aaagggttct gccgggtctc ggcatggccc 18900
gcgggcaggg acacgttgcg gaactggtac ttggccagcc acttgaactc ggggatcagc 18960
agtttgggca gcggggtgtc ggggaaggag tcggtccaca gcttccgcgt cagctgcagg 19020
gcgcccagca ggtcgggcgc ggagatcttg aaatcgcagt tgggacccgc gttctgcgcg 19080
cgagagttgc ggtacacggg gttgcagcac tggaacacca tcagggccgg gtgcttcacg 19140
ctcgccagca ccgccgcgtc ggtgatgctc tccacgtcga ggtcctcggc gttggccatc 19200
ccgaaggggg tcatcttgca ggtctgcctt cccatggtgg gcacgcaccc gggcttgtgg 19260
ttgcaatcgc agtgcagggg gatcagcatc atctgggcct ggtcggcgtt catccccggg 19320
tacatggcct tcatgaaagc ctccaattgc ctgaacgcct gctgggcctt ggctccctcg 19380
gtgaagaaga ccccgcagga cttgctagag aactggttgg tggcacagcc ggcatcgtgc 19440
acgcagcagc gcgcgtcgtt gttggccagc tgcaccacgc tgcgccccca gcggttctgg 19500
gtgatcttgg cccggtcggg gttctccttc agcgcgcgct gcccgttctc gctcgccaca 19560
tccatctcga tcatgtgctc cttctggatc atggtggtcc cgtgcaggca ccgcagtttg 19620
ccctcggcct cggtgcaccc gtgcagccac agcgcgcacc cggtgcactc ccagttcttg 19680
tgggcgatct gggaatgcgc gtgcacgaac ccttgcagga agcggcccat catggtcgtc 19740
agggtcttgt tgctagtgaa ggtcaacggg atgccgcggt gctcctcgtt gatgtacagg 19800
tggcagatgc ggcggtacac ctcgccctgc tcgggcatca gttggaagtt ggctttcagg 19860
tcggtctcca cgcggtagcg gtccatcagc atagtcatga tttccatgcc cttctcccag 19920
gccgagacga tgggcaggct catagggttc ttcaccatca tcttagcact agcagccgcg 19980
gccagggggt cgctctcatc cagggtctca aagctccgct tgccgtcctt ctcggtgatc 20040
cgcaccgggg ggtagctgaa gcccacggcc gccagctcct cctcggcctg tctttcgtcc 20100
tcgctgtcct ggctgacgtc ctgcatgacc acatgcttgg tcttgcgggg tttcttcttg 20160
ggcggcagtg gcggcggaga tgcttgtggc gagggggagc gcgagttctc gctcaccact 20220
actatctctt cctcttcttg gtccgaggcc acgcggcggt aggtatgtct cttcgggggc 20280
agaggcggag gcgacgggct ctcgccgccg cgacttggcg gatggctggc agagcccctt 20340
ccgcgttcgg gggtgcgctc ccggcggcgc tctgactgac ttcctccgcg gccggccatt 20400
gtgttctcct agggaggaac aacaagcatg gagactcagc catcgccaac ctcgccatct 20460
gcccccaccg ccggcgacga gaagcagcag cagcagaatg aaagcttaac cgccccgccg 20520
cccagccccg cctccgacgc agccgcggtc ccagacatgc aagagatgga ggaatccatc 20580
gagattgacc tgggctatgt gacgcccgcg gagcatgagg aggagctggc agtgcgcttt 20640
caatcgtcaa gccaggaaga taaagaacag ccagagcagg aagcagagaa cgagcagagt 20700
caggctgggc tcgagcatgg cgactacctc cacctgagcg gggaggagga cgcgctcatc 20760
aagcatctgg cccggcaggc caccatcgtc aaggacgcgc tgctcgaccg caccgaggtg 20820
cccctcagcg tggaggagct cagccgcgcc tacgagctca acctcttctc gccgcgcgtg 20880
ccccccaagc gccagcccaa cggcacctgc gagcccaacc cccgcctcaa cttctacccg 20940
gtcttcgcgg tgcccgaggc cctggccacc taccacatct ttttcaagaa ccaaaagatc 21000
cccgtctcct gccgcgccaa ccgcacccgc gccgacgccc tcttcaacct gggtcccggc 21060
gcccgcctac ctgatatcgc ctccttggaa gaggttccca agatcttcga gggtctgggc 21120
agcgacgaga ctcgggccgc gaacgctctg caaggagaag gaggaggaga gcatgagcac 21180
cacagcgccc tggtcgagtt ggaaggcgac aacgcgcggc tggcggtgct caaacgcacg 21240
gtcgagctga cccatttcgc ctacccggct ctgaacctgc ccccgaaagt catgagcgcg 21300
gtcatggacc aggtgctcat caagcgcgcg tcgcccatct ccgaggacga gggcatgcaa 21360
gactccgagg agggcaagcc cgtggtcagc gacgagcagc tggcccggtg gctgggtcct 21420
aatgctaccc ctcaaagttt ggaagagcgg cgcaagctca tgatggccgt ggtcctggtg 21480
accgtggagc tggagtgcct gcgccgcttc ttcgccgacg cggagaccct gcgcaaggtc 21540
gaggagaacc tgcactacct cttcaggcac gggttcgtgc gccaggcctg caagatctcc 21600
aacgtggagc tgaccaacct ggtctcctac atgggcatct tgcacgagaa ccgcctgggg 21660
cagaacgtgc tgcacaccac cctgcgcggg gaggcccgcc gcgactacat ccgcgactgc 21720
gtctacctct acctctgcca cacctggcag acgggcatgg gcgtgtggca gcagtgtctg 21780
gaggagcaga acctgaaaga gctctgcaag ctcctgcaaa agaacctcaa gggtctgtgg 21840
accgggttcg acgagcggac caccgcctcg gacctggccg acctcatctt ccccgagcgc 21900
ctcaggctga cgctgcgcaa cggcctgccc gactttatga gccaaagcat gttgcaaaac 21960
tttcgctctt tcatcctcga acgctccgga atcctgcccg ccacctgctc cgcgctgccc 22020
tcggacttcg tgccgctgac cttccgcgag tgccccccgc cgctgtggag ccactgctac 22080
ctgctgcgcc tggccaacta cctggcctac cactcggacg tgatcgagga cgtcagcggc 22140
gagggcctgc tcgagtgcca ctgccgctgc aacctctgca cgccgcaccg ctccctggcc 22200
tgcaaccccc agctgctgag cgagacccag atcatcggca ccttcgagtt gcaagggccc 22260
agcgagggcg agggagccaa ggggggtctg aaactcaccc cggggctgtg gacctcggcc 22320
tacttgcgca agttcgtgcc cgaggattac catcccttcg agatcaggtt ctacgaggac 22380
caatcccagc cgcccaaggc cgagctgtcg gcctgcgtca tcacccaggg ggcgatcctg 22440
gcccaattgc aagccatcca gaaatcccgc caagaattct tgctgaaaaa gggccgcggg 22500
gtctacctcg acccccagac cggtgaggag ctcaaccccg gcttccccca ggatgccccg 22560
aggaaacaag aagctgaaag tggagctgcc gcccgtggag gatttggagg aagactggga 22620
gaacagcagt caggcagagg agatggagga agactgggac agcactcagg cagaggagga 22680
cagcctgcaa gacagtctgg aggaagacga ggaggaggca gaggaggagg tggaagaagc 22740
agccgccgcc agaccgtcgt cctcggcggg ggagaaagca agcagcacgg ataccatctc 22800
cgctccgggt cggggtcccg ctcggcccca cagtagatgg gacgagaccg ggcgattccc 22860
gaaccccacc acccagaccg gtaagaagga gcggcaggga tacaagtcct ggcgggggca 22920
caaaaacgcc atcgtctcct gcttgcaggc ctgcgggggc aacatctcct tcacccggcg 22980
ctacctgctc ttccaccgcg gggtgaactt cccccgcaac atcttgcatt actaccgtca 23040
cctccacagc ccctactact tccaagaaga ggcagcagca gcagaaaaag accagaaaac 23100
cagctagaaa atccacagcg gcggcagcgg caggtggact gaggatcgcg gcgaacgagc 23160
cggcgcagac ccgggagctg aggaaccgga tctttcccac cctctatgcc atcttccagc 23220
agagtcgggg gcaggagcag gaactgaaag tcaagaaccg ttctctgcgc tcgctcaccc 23280
gcagttgtct gtatcacaag agcgaagacc aacttcagcg cactctcgag gacgccgagg 23340
ctctcttcaa caagtactgc gcgctcactc ttaaagagta gcccgcgccc gcccagtcgc 23400
agaaaaaggc gggaattacg tcacctgtgc ccttcgccct agccgcctcc acccagcacc 23460
gccatgagca aagagattcc cacgccttac atgtggagct accagcccca gatgggcctg 23520
gccgccggcg ccgcccagga ctactccacc cgcatgaatt ggctcagcgc cgggcccgcg 23580
atgatctcac gggtgaatga catccgcgcc caccgaaacc agatactcct agaacagtca 23640
gcgctcaccg ccacgccccg caatcacctc aatccgcgta attggcccgc cgccctggtg 23700
taccaggaaa ttccccagcc cacgaccgta ctacttccgc gagacgccca ggccgaagtc 23760
cagctgacta actcaggtgt ccagctggcg ggcggcgcca ccctgtgtcg tcaccgcccc 23820
gctcagggta taaagcggct ggtgatccgg ggcagaggca cacagctcaa cgacgaggtg 23880
gtgagctctt cgctgggtct gcgacctgac ggagtcttcc aactcgccgg atcggggaga 23940
tcttccttca cgcctcgtca ggcggtcctg actttggaga gttcgtcctc gcagccccgc 24000
tcgggcggca tcggcactct ccagttcgtg gaggagttca ctccctcggt ctacttcaac 24060
cccttctccg gctcccccgg ccactacccg gacgagttca tcccgaactt tgacgccatc 24120
agcgagtcgg tggacggcta cgattgatta attaatcaac taacccctta cccctttacc 24180
ctccagtaaa aataaagatt aaaaatgatt gaattgatca ataaagaatc acttacttga 24240
aatctgaaac caggtctctg tccatgtttt ctgtcagcag cacttcactc ccctcttccc 24300
aactctggta ctgcaggccc cggcgggctg caaacttcct ccacactctg aaggggatgt 24360
caaattcctc ctgtccctca atcttcattt ttatcttcta tcagatgtcc aaaaagcgcg 24420
cgcgggtgga tgatggcttc gaccccgtgt acccctacga tgcagacaac gcaccgactg 24480
tgcccttcat caaccctccc ttcgtctctt cagatggatt ccaagaaaag cccctggggg 24540
tgttgtccct gcgactggcc gaccccgtca ccaccaagaa tggggctgtc accctcaagc 24600
tgggggaggg ggtggacctc gacgactcgg gaaaactcat ctccaaaaat gccaccaagg 24660
ccactgcccc tctcagtatt tccaacggca ccatttccct taacatggct gccccttttt 24720
acaacaacaa tggaacgtta agtctcaatg tttctacacc attagcagta tttcccactt 24780
ttaacacttt aggtatcagt cttggaaacg gtcttcaaac ttctaataag ttgctgactg 24840
tacagttaac tcatcctctt acattcagct caaatagcat cacagtaaaa acagacaaag 24900
gactctatat taattctagt ggaaacagag ggcttgaggc taacataagc ctaaaaagag 24960
gactgatttt tgatggtaat gctattgcaa cataccttgg aagtggttta gactatggat 25020
cctatgatag cgatgggaaa acaagaccca tcatcaccaa aattggagca ggtttgaatt 25080
ttgatgctaa taatgccatg gctgtgaagc taggcacagg tttaagtttt gactctgccg 25140
gtgccttaac agctggaaac aaagaggatg acaagctaac actttggact acacctgacc 25200
caagccctaa ttgtcaatta ctttcagaca gagatgccaa atttacccta tgtcttacaa 25260
aatgcggtag tcaaatacta ggcactgttg cagtagctgc tgttactgta ggttcagcac 25320
taaatccaat taatgacaca gtaaaaagcg ccatagtatt ccttagattt gactctgacg 25380
gtgtgctcat gtcaaactca tcaatggtag gtgattactg gaactttagg gaaggacaga 25440
ccacccaaag tgtggcctat acaaatgctg tgggattcat gcccaatcta ggtgcatatc 25500
ctaaaaccca aagcaaaaca ccaaaaaata gtatagtaag tcaggtatat ttaaatggag 25560
aaactactat gccaatgaca ctgacaataa ctttcaatgg cactgatgaa aaagacacaa 25620
cacctgtgag cacttactcc atgactttta catggcagtg gactggagac tataaggaca 25680
agaatattac ctttgctacc aactccttta ctttctccta catggcccaa gaataaaccc 25740
tgcatgccaa ccccattgtt cccaccacta tggaaaactc tgaagcagaa aaaaataaag 25800
ttcaagtgtt ttattgattc aacagttttc tcacagaacc ctagtattca acctgccacc 25860
tccctcccaa cacacagagt acacagtcct ttctccccgg ctggccttaa aaagcatcat 25920
atcatgggta acagacatat tcttaggtgt tatattccac acggtttcct gtcgagccaa 25980
acgctcatca gtgatattaa taaactcccc gggcagctca cttaagttca tgtcgctgtc 26040
cagctgctga gccacaggct gctgtccaac ttgcggttgc ttaacgggcg gcgaaggaga 26100
agtccacgcc tacatggggg tagagtcata atcgtgcatc aggatagggc ggtggtgctg 26160
cagcagcgcg cgaataaact gctgccgccg ccgctccgtc ctgcaggaat acaacatggc 26220
agtggtctcc tcagcgatga ttcgcaccgc ccgcagcata aggcgccttg tcctccgggc 26280
acagcagcgc accctgatct cacttaaatc agcacagtaa ctgcagcaca gcaccacaat 26340
attgttcaaa atcccacagt gcaaggcgct gtatccaaag ctcatggcgg ggaccacaga 26400
acccacgtgg ccatcatacc acaagcgcag gtagattaag tggcgacccc tcataaacac 26460
gctggacata aacattacct cttttggcat gttgtaattc accacctccc ggtaccatat 26520
aaacctctga ttaaacatgg cgccatccac caccatccta aaccagctgg ccaaaacctg 26580
cccgccggct atacactgca gggaaccggg actggaacaa tgacagtgga gagcccagga 26640
ctcgtaacca tggatcatca tgctcgtcat gatatcaatg ttggcacaac acaggcacac 26700
gtgcatacac ttcctcagga ttacaagctc ctcccgcgtt agaaccatat cccagggaac 26760
aacccattcc tgaatcagcg taaatcccac actgcaggga agacctcgca cgtaactcac 26820
gttgtgcatt gtcaaagtgt tacattcggg cagcagcgga tgatcctcca gtatggtagc 26880
gcgggtttct gtctcaaaag gaggtagacg atccctactg tacggagtgc gccgagacaa 26940
ccgagatcgt gttggtcgta gtgtcatgcc aaatggaacg ccggacgtag tcatatttcc 27000
tgaagcaaaa ccaggtgcgg gcgtgacaaa cagatctgcg tctccggtct cgccgcttag 27060
atcgctctgt gtagtagttg tagtatatcc actctctcaa agcatccagg cgccccctgg 27120
cttcgggttc tatgtaaact ccttcatgcg ccgctgccct gataacatcc accaccgcag 27180
aataagccac acccagccaa cctacacatt cgttctgcga gtcacacacg ggaggagcgg 27240
gaagagctgg aagaaccatg attaacttta ttccaaacgg tctcggagca cttcaaaatg 27300
caggtcccgg aggtggcacc tctcgccccc actgtgttgg tggaaaataa cagccaggtc 27360
aaaggtgaca cggttctcga gatgttccac ggtggcttcc agcaaagcct ccacgcgcac 27420
atccagaaac aagaggacag cgaaagcggg agcgttttct aattcctcaa tcatcatatt 27480
acactcctgc accatcccca gataattttc atttttccag ccttgaatga ttcgtattag 27540
ttcctgaggt aaatccaagc cagccatgat aaaaagctcg cgcagagcgc cctccaccgg 27600
cattcttaag cacaccctca taattccaag agattctgct cctggttcac ctgcagcaga 27660
ttaacaatgg gaatatcaaa atctctgccg cgatccctaa gctcctccct caacaataac 27720
tgtatgtaat ctttcatatc atctccgaaa tttttagcca tagggccgcc aggaataaga 27780
gcagggcaag ccacattaca gataaagcga agtcctcccc agtgwgcatt gccaaatgta 27840
agattgaaat aagcatgctg gctagaccct gtgatatctt ccagataact ggacagaaaa 27900
tcaggcaagc aatttttaag aaaatcaaca aaagaaaagt cgtccaggtg caggtttaga 27960
gcctcaggaa caacgatgga ataagtgcaa ggagtgcgtt ccagcatggt tagtgttttt 28020
ttggtgatct gtagaacaaa aaataaacat gcaatattaa accatgctag cctggcgaac 28080
aggtgggtaa atcactcttt ccagcaccag gcaggctacg gggtctccgg cgcgaccctc 28140
gtagaagctg tcgccatgat tgaaaagcat caccgagaga ccttcccggt ggccggcatg 28200
gatgattcga gaagaagcat acactccggg aacattggca tccgtgagtg aaaaaaagcg 28260
acctataaag cctcggggca ctacaatgct caatctcaat tccagcaaag ccaccccatg 28320
cggatggagc acaaaattgg caggtgcgta aaaaatgtaa ttactcccct cctgcacagg 28380
cagcaaagcc cccgctccct ccagaaacac atacaaagcc tcagcgtcca tagcttaccg 28440
agcacggcag gcgcaagagt cagagaaaag gctgagctct aacctgactg cccgctcctg 28500
tgctcaatat atagccctaa cctacactga cgtaaaggcc aaagtctaaa aatacccgcc 28560
aaaatgacac acacgcccag cacacgccca gaaaccggtg acacactcaa aaaaatacgt 28620
gcgcttcctc aaacgcccaa accggcgtca tttccgggtt cccacgctac gtcaccgctc 28680
agcgactttc aaattccgtc gaccgttaaa aacgtcactc gccccgcccc taacggtcgc 28740
ccttctctcg gccaatcacc ttcctccctt cccaaattca aacgcctcat ttgcatatta 28800
acgcgcacaa aaagtttgag gtatatattt gaatgatggt ttaaacgcgg ccgccaggcc 28860
tacccactag tcaattcggg aggatcgaaa cggcagatcg caaaaaacag tacatacaga 28920
aggagacatg aacatgaaca tcaaaaaaat tgtaaaacaa gccacagttc tgacttttac 28980
gactgcactt ctggcaggag gagcgactca agccttcgcg aaagaaaata accaaaaagc 29040
atacaaagaa acgtacggcg tctctcatat tacacgccat gatatgctgc agatccctaa 29100
acagcagcaa aacgaaaaat accaagtgcc tcaattcgat caatcaacga ttaaaaataa 29160
ttgagtctga caaaaggact tgatgtg 29187
<210> 41
<211> 2661
<212> DNA
<213> 人工序列
<220>
<223> 载体
<400> 41
ttaattaacc atcttcaata atatacctca aactttttgt gcgcgttaat atgcaaatga 60
ggcgtttgaa tttggggagg aagggcggtg attggtcgag ggatgagcga ccgttagggg 120
cggggcgagt gacgttttga tgacgtggtt gcgaggagga gccagtttgc aagttctcgt 180
gggaaaagtg acgtcaaacg aggtgtggtt tgaacacgga aatactcaat tttcccgcgc 240
tctctgacag gaaatgaggt gtttctgggc ggatgcaagt gaaaacgggc cattttcgcg 300
cgaaaactga atgaggaagt gaaaatctga gtaatttcgc gtttatggca gggaggagta 360
tttgccgagg gccgagtaga ctttgaccga ttacgtgggg gtttcgatta ccgtgttttt 420
cacctaaatt tccgcgtacg gtgtcaaagt ccggtgtttt tacgcgatcg ctagcgacat 480
cgatcacaag tttgtacaaa aaagcaggct ccaccatggg aacccgcgtt ttgagatttc 540
tgtcgccgac taaattcatg tcgcgcgata gtggtgttta tcgccgatag agatggcgat 600
attggaaaaa tcgatatttg aaaatatggc atattgaaaa tgtcgccgat gtgagtttct 660
gtgtaactga tatcgccatt tttccaaaag tgatttttgg gcatacgcga tatctggcga 720
tagcgcttat atcgtttacg ggggatggcg atagacgact ttggtgactt gggcgattct 780
gtgtgtcgca aatatcgcag tttcgatata ggtgacagac gatatgaggc tatatcgccg 840
atagaggcga catcaagctg gcacatggcc aatgcatatc gatctataca ttgaatcaat 900
attggccatt agccatatta ttcattggtt atatagcata aatcaatatt ggctattggc 960
cattgcatac gttgtatcca tatcataata tgtacattta tattggctca tgtccaacat 1020
taccgccatg ttgacattga ttattgacta gttattaata gtaatcaatt acggggtcat 1080
tagttcatag cccatatatg gagttccgcg ttacataact tacggtaaat ggcccgcctg 1140
gctgaccgcc caacgacccc cgcccattga cgtcaataat gacgtatgtt cccatagtaa 1200
cgccaatagg gactttccat tgacgtcaat gggtggagta tttacggtaa actgcccact 1260
tggcagtaca tcaagtgtat catatgccaa gtacgccccc tattgacgtc aatgacggta 1320
aatggcccgc ctggcattat gcccagtaca tgaccttatg ggactttcct acttggcagt 1380
acatctacgt attagtcatc gctattacca tggtgatgcg gttttggcag tacatcaatg 1440
ggcgtggata gcggtttgac tcacggggat ttccaagtct ccaccccatt gacgtcaatg 1500
ggagtttgtt ttggcaccaa aatcaacggg actttccaaa atgtcgtaac aactccgccc 1560
cattgacgca aatgggcggt aggcgtgtac ggtgggaggt ctatataagc agagctctcc 1620
ctatcagtga tagagatctc cctatcagtg atagagatcg tcgacgagct cgtttagtga 1680
accgtcagat cgcctggaga cgccatccac gctgttttga cctccataga agacaccggg 1740
accgatccag cctccgcggc cgggaacggt gcattggaac gcggattccc cgtgccaaga 1800
gtgacgtaag taccgcctat agagtctata ggcccacccc cttggcttct tatgcatgct 1860
atactgtttt tggcttgggg tctatacacc cccgcttcct catgttatag gtgatggtat 1920
agcttagcct ataggtgtgg gttattgacc attattgacc actcccctat tggtgacgat 1980
actttccatt actaatccat aacatggctc tttgccacaa ctctctttat tggctatatg 2040
ccaatacact gtccttcaga gactgacacg gactctgtat ttttacagga tggggtctca 2100
tttattattt acaaattcac atatacaaca ccaccgtccc cagtgcccgc agtttttatt 2160
aaacataacg tgggatctcc acgcgaatct cgggtacgtg ttccggacat gggctcttct 2220
ccggtagcgg cggagcttct acatccgagc cctgctccca tgcctccagc gactcatggt 2280
cgctcggcag ctccttgctc ctaacagtgg aggccagact taggcacagc acgatgccca 2340
ccaccaccag tgtgccgcac aaggccgtgg cggtagggta tgtgtctgaa aatgagctcg 2400
gggagcgggc ttgcaccgct gacgcatttg gaagacttaa ggcagcggca gaagaagatg 2460
caggcagctg agttgttgtg ttctgataag agtcagaggt aactcccgtt gcggtgctgt 2520
taacggtgga gggcagtgta gtctgagcag tactcgttgc tgccgcgcgc gccaccagac 2580
ataatagctg acagactaac agactgttcc tttccatggg tcttttctgc agtcaccgtc 2640
cttgacacga agcttggtac c 2661
<210> 42
<211> 37490
<212> DNA
<213> 人工序列
<220>
<223> 载体
<400> 42
gcggccgctc gagcatgcat ctagagggcc ctattctata gtgtcaccta aatgctagag 60
ctcgctgatc agcctcgact gtgccttcta gttgccagcc atctgttgtt tgcccctccc 120
ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt cctttcctaa taaaatgagg 180
aaattgcatc gcattgtctg agtaggtgtc attctattct ggggggtggg gtggggcagg 240
acagcaaggg ggaggattgg gaagacaata gcaggcatgc tggggatgcg gtgggctcta 300
tggcttctga ggcggaaaga accagctggg gctcgagggg ggatcgatcc cgtcgagata 360
tctagaccca gctttcttgt acaaagtggt gatcgattcg acagatcgcg atcgcaagtg 420
agtagtgttc tggggcgggg gaggacctgc atgagggcca gaataactga aatctgtgct 480
tttctgtgtg ttgcagcagc atgagcggaa gcggctcctt tgagggaggg gtattcagcc 540
cttatctgac ggggcgtctc ccctcctggg cgggagtgcg tcagaatgtg atgggatcca 600
cggtggacgg ccggcccgtg cagcccgcga actcttcaac cctgacctat gcaaccctga 660
gctcttcgtc gttggacgca gctgccgccg cagctgctgc atctgccgcc agcgccgtgc 720
gcggaatggc catgggcgcc ggctactacg gcactctggt ggccaactcg agttccacca 780
ataatcccgc cagcctgaac gaggagaagc tgttgctgct gatggcccag ctcgaggcct 840
tgacccagcg cctgggcgag ctgacccagc aggtggctca gctgcaggag cagacgcggg 900
ccgcggttgc cacggtgaaa tccaaataaa aaatgaatca ataaataaac ggagacggtt 960
gttgatttta acacagagtc tgaatcttta tttgattttt cgcgcgcggt aggccctgga 1020
ccaccggtct cgatcattga gcacccggtg gatcttttcc aggacccggt agaggtgggc 1080
ttggatgttg aggtacatgg gcatgagccc gtcccggggg tggaggtagc tccattgcag 1140
ggcctcgtgc tcgggggtgg tgttgtaaat cacccagtca tagcaggggc gcagggcatg 1200
gtgttgcaca atatctttga ggaggagact gatggccacg ggcagccctt tggtgtaggt 1260
gtttacaaat ctgttgagct gggagggatg catgcggggg gagatgaggt gcatcttggc 1320
ctggatcttg agattggcga tgttaccgcc cagatcccgc ctggggttca tgttgtgcag 1380
gaccaccagc acggtgtatc cggtgcactt ggggaattta tcatgcaact tggaagggaa 1440
ggcgtgaaag aatttggcga cgcctttgtg cccgcccagg ttttccatgc actcatccat 1500
gatgatggcg atgggcccgt gggcggcggc ctgggcaaag acgtttcggg ggtcggacac 1560
atcatagttg tggtcctggg tgaggtcatc ataggccatt ttaatgaatt tggggcggag 1620
ggtgccggac tgggggacaa aggtaccctc gatcccgggg gcgtagttcc cctcacagat 1680
ctgcatctcc caggctttga gctcggaggg ggggatcatg tccacctgcg gggcgataaa 1740
gaacacggtt tccggggcgg gggagatgag ctgggccgaa agcaagttcc ggagcagctg 1800
ggacttgccg cagccggtgg ggccgtagat gaccccgatg accggctgca ggtggtagtt 1860
gagggagaga cagctgccgt cctcccggag gaggggggcc acctcgttca tcatctcgcg 1920
cacgtgcatg ttctcgcgca ccagttccgc caggaggcgc tctcccccca gggataggag 1980
ctcctggagc gaggcgaagt ttttcagcgg cttgagtccg tcggccatgg gcattttgga 2040
gagggtttgt tgcaagagtt ccaggcggtc ccagagctcg gtgatgtgct ctacggcatc 2100
tcgatccagc agacctcctc gtttcgcggg ttgggacggc tgcgggagta gggcaccaga 2160
cgatgggcgt ccagcgcagc cagggtccgg tccttccagg gtcgcagcgt ccgcgtcagg 2220
gtggtctccg tcacggtgaa ggggtgcgcg ccgggctggg cgcttgcgag ggtgcgcttc 2280
aggctcatcc ggctggtcga aaaccgctcc cgatcggcgc cctgcgcgtc ggccaggtag 2340
caattgacca tgagttcgta gttgagcgcc tcggccgcgt ggcctttggc gcggagctta 2400
cctttggaag tctgcccgca ggcgggacag aggagggact tgagggcgta gagcttgggg 2460
gcgaggaaga cggactcggg ggcgtaggcg tccgcgccgc agtgggcgca gacggtctcg 2520
cactccacga gccaggtgag gtcgggctgg tcggggtcaa aaaccagttt cccgccgttc 2580
tttttgatgc gtttcttacc tttggtctcc atgagctcgt gtccccgctg ggtgacaaag 2640
aggctgtccg tgtccccgta gaccgacttt atgggccggt cctcgagcgg tgtgccgcgg 2700
tcctcctcgt agaggaaccc cgcccactcc gagacgaaag cccgggtcca ggccagcacg 2760
aaggaggcca cgtgggacgg gtagcggtcg ttgtccacca gcgggtccac cttttccagg 2820
gtatgcaaac acatgtcccc ctcgtccaca tccaggaagg tgattggctt gtaagtgtag 2880
gccacgtgac cgggggtccc ggccgggggg gtataaaagg gtgcgggtcc ctgctcgtcc 2940
tcactgtctt ccggatcgct gtccaggagc gccagctgtt ggggtaggta ttccctctcg 3000
aaggcgggca tgacctcggc actcaggttg tcagtttcta gaaacgagga ggatttgata 3060
ttgacggtgc cggcggagat gcctttcaag agcccctcgt ccatctggtc agaaaagacg 3120
atctttttgt tgtcgagctt ggtggcgaag gagccgtaga gggcgttgga gaggagcttg 3180
gcgatggagc gcatggtctg gtttttttcc ttgtcggcgc gctccttggc ggcgatgttg 3240
agctgcacgt actcgcgcgc cacgcacttc cattcgggga agacggtggt cagctcgtcg 3300
ggcacgattc tgacctgcca gccccgatta tgcagggtga tgaggtccac actggtggcc 3360
acctcgccgc gcaggggctc attagtccag cagaggcgtc cgcccttgcg cgagcagaag 3420
gggggcaggg ggtccagcat gacctcgtcg ggggggtcgg catcgatggt gaagatgccg 3480
ggcaggaggt cggggtcaaa gtagctgatg gaagtggcca gatcgtccag ggcagcttgc 3540
cattcgcgca cggccagcgc gcgctcgtag ggactgaggg gcgtgcccca gggcatggga 3600
tgggtaagcg cggaggcgta catgccgcag atgtcgtaga cgtagagggg ctcctcgagg 3660
atgccgatgt aggtggggta gcagcgcccc ccgcggatgc tggcgcgcac gtagtcatac 3720
agctcgtgcg agggggcgag gagccccggg cccaggttgg tgcgactggg cttttcggcg 3780
cggtagacga tctggcggaa aatggcatgc gagttggagg agatggtggg cctttggaag 3840
atgttgaagt gggcgtgggg cagtccgacc gagtcgcgga tgaagtgggc gtaggagtct 3900
tgcagcttgg cgacgagctc ggcggtgact aggacgtcca gagcgcagta gtcgagggtc 3960
tcctggatga tgtcatactt gagctgtccc ttttgtttcc acagctcgcg gttgagaagg 4020
aactcttcgc ggtccttcca gtactcttcg agggggaacc cgtcctgatc tgcacggtaa 4080
gagcctagca tgtagaactg gttgacggcc ttgtaggcgc agcagccctt ctccacgggg 4140
agggcgtagg cctgggcggc cttgcgcagg gaggtgtgcg tgagggcgaa agtgtccctg 4200
accatgacct tgaggaactg gtgcttgaag tcgatatcgt cgcagccccc ctgctcccag 4260
agctggaagt ccgtgcgctt cttgtaggcg gggttgggca aagcgaaagt aacatcgttg 4320
aagaggatct tgcccgcgcg gggcataaag ttgcgagtga tgcggaaagg ttggggcacc 4380
tcggcccggt tgttgatgac ctgggcggcg agcacgatct cgtcgaagcc gttgatgttg 4440
tggcccacga tgtagagttc cacgaatcgc ggacggccct tgacgtgggg cagtttcttg 4500
agctcctcgt aggtgagctc gtcggggtcg ctgagcccgt gctgctcgag cgcccagtcg 4560
gcgagatggg ggttggcgcg gaggaaggaa gtccagagat ccacggccag ggcggtttgc 4620
agacggtccc ggtactgacg gaactgctgc ccgacggcca ttttttcggg ggtgacgcag 4680
tagaaggtgc gggggtcccc gtgccagcga tcccatttga gctggagggc gagatcgagg 4740
gcgagctcga cgagccggtc gtccccggag agtttcatga ccagcatgaa ggggacgagc 4800
tgcttgccga aggaccccat ccaggtgtag gtttccacat cgtaggtgag gaagagcctt 4860
tcggtgcgag gatgcgagcc gatggggaag aactggatct cctgccacca attggaggaa 4920
tggctgttga tgtgatggaa gtagaaatgc cgacggcgcg ccgaacactc gtgcttgtgt 4980
ttatacaagc ggccacagtg ctcgcaacgc tgcacgggat gcacgtgctg cacgagctgt 5040
acctgagttc ctttgacgag gaatttcagt gggaagtgga gtcgtggcgc ctgcatctcg 5100
tgctgtacta cgtcgtggtg gtcggcctgg ccctcttctg cctcgatggt ggtcatgctg 5160
acgagcccgc gcgggaggca ggtccagacc tcggcgcgag cgggtcggag agcgaggacg 5220
agggcgcgca ggccggagct gtccagggtc ctgagacgct gcggagtcag gtcagtgggc 5280
agcggcggcg cgcggttgac ttgcaggagt ttttccaggg cgcgcgggag gtccagatgg 5340
tacttgatct ccaccgcgcc attggtggcg acgtcgatgg cttgcagggt cccgtgcccc 5400
tggggtgtga ccaccgtccc ccgtttcttc ttgggcggct ggggcgacgg gggcggtgcc 5460
tcttccatgg ttagaagcgg cggcgaggac gcgcgccggg cggcaggggc ggctcggggc 5520
ccggaggcag gggcggcagg ggcacgtcgg cgccgcgcgc gggtaggttc tggtactgcg 5580
cccggagaag actggcgtga gcgacgacgc gacggttgac gtcctggatc tgacgcctct 5640
gggtgaaggc cacgggaccc gtgagtttga acctgaaaga gagttcgaca gaatcaatct 5700
cggtatcgtt gacggcggcc tgccgcagga tctcttgcac gtcgcccgag ttgtcctggt 5760
aggcgatctc ggtcatgaac tgctcgatct cctcctcttg aaggtctccg cggccggcgc 5820
gctccacggt ggccgcgagg tcgttggaga tgcggcccat gagctgcgag aaggcgttca 5880
tgcccgcctc gttccagacg cggctgtaga ccacgacgcc ctcgggatcg ccggcgcgca 5940
tgaccacctg ggcgaggttg agctccacgt ggcgcgtgaa gaccgcgtag ttgcagaggc 6000
gctggtagag gtagttgagc gtggtggcga tgtgctcggt gacgaagaaa tacatgatcc 6060
agcggcggag cggcatctcg ctgacgtcgc ccagcgcctc caaacgttcc atggcctcgt 6120
aaaagtccac ggcgaagttg aaaaactggg agttgcgcgc cgagacggtc aactcctcct 6180
ccagaagacg gatgagctcg gcgatggtgg cgcgcacctc gcgctcgaag gcccccggga 6240
gttcctccac ttcctcttct tcctcctcca ctaacatctc ttctacttcc tcctcaggcg 6300
gcagtggtgg cgggggaggg ggcctgcgtc gccggcggcg cacgggcaga cggtcgatga 6360
agcgctcgat ggtctcgccg cgccggcgtc gcatggtctc ggtgacggcg cgcccgtcct 6420
cgcggggccg cagcgtgaag acgccgccgc gcatctccag gtggccgggg gggtccccgt 6480
tgggcaggga gagggcgctg acgatgcatc ttatcaattg ccccgtaggg actccgcgca 6540
aggacctgag cgtctcgaga tccacgggat ctgaaaaccg ctgaacgaag gcttcgagcc 6600
agtcgcagtc gcaaggtagg ctgagcacgg tttcttctgg cgggtcatgt tggttgggag 6660
cggggcgggc gatgctgctg gtgatgaagt tgaaataggc ggttctgaga cggcggatgg 6720
tggcgaggag caccaggtct ttgggcccgg cttgctggat gcgcagacgg tcggccatgc 6780
cccaggcgtg gtcctgacac ctggccaggt ccttgtagta gtcctgcatg agccgctcca 6840
cgggcacctc ctcctcgccc gcgcggccgt gcatgcgcgt gagcccgaag ccgcgctggg 6900
gctggacgag cgccaggtcg gcgacgacgc gctcggcgag gatggcttgc tggatctggg 6960
tgagggtggt ctggaagtca tcaaagtcga cgaagcggtg gtaggctccg gtgttgatgg 7020
tgtaggagca gttggccatg acggaccagt tgacggtctg gtggcccgga cgcacgagct 7080
cgtggtactt gaggcgcgag taggcgcgcg tgtcgaagat gtagtcgttg caggtgcgca 7140
ccaggtactg gtagccgatg aggaagtgcg gcggcggctg gcggtagagc ggccatcgct 7200
cggtggcggg ggcgccgggc gcgaggtcct cgagcatggt gcggtggtag ccgtagatgt 7260
acctggacat ccaggtgatg ccggcggcgg tggtggaggc gcgcgggaac tcgcggacgc 7320
ggttccagat gttgcgcagc ggcaggaagt agttcatggt gggcacggtc tggcccgtga 7380
ggcgcgcgca gtcgtggatg ctctatacgg gcaaaaacga aagcggtcag cggctcgact 7440
ccgtggcctg gaggctaagc gaacgggttg ggctgcgcgt gtaccccggt tcgaatctcg 7500
aatcaggctg gagccgcagc taacgtggta ttggcactcc cgtctcgacc caagcctgca 7560
ccaaccctcc aggatacgga ggcgggtcgt tttgcaactt ttttttggag gccggatgag 7620
actagtaagc gcggaaagcg gccgaccgcg atggctcgct gccgtagtct ggagaagaat 7680
cgccagggtt gcgttgcggt gtgccccggt tcgaggccgg ccggattccg cggctaacga 7740
gggcgtggct gccccgtcgt ttccaagacc ccatagccag ccgacttctc cagttacgga 7800
gcgagcccct cttttgtttt gtttgttttt gccagatgca tcccgtactg cggcagatgc 7860
gcccccacca ccctccaccg caacaacagc cccctccaca gccggcgctt ctgcccccgc 7920
cccagcagca acttccagcc acgaccgccg cggccgccgt gagcggggct ggacagagtt 7980
atgatcacca gctggccttg gaagagggcg aggggctggc gcgcctgggg gcgtcgtcgc 8040
cggagcggca cccgcgcgtg cagatgaaaa gggacgctcg cgaggcctac gtgcccaagc 8100
agaacctgtt cagagacagg agcggcgagg agcccgagga gatgcgcgcg gcccggttcc 8160
acgcggggcg ggagctgcgg cgcggcctgg accgaaagag ggtgctgagg gacgaggatt 8220
tcgaggcgga cgagctgacg gggatcagcc ccgcgcgcgc gcacgtggcc gcggccaacc 8280
tggtcacggc gtacgagcag accgtgaagg aggagagcaa cttccaaaaa tccttcaaca 8340
accacgtgcg caccctgatc gcgcgcgagg aggtgaccct gggcctgatg cacctgtggg 8400
acctgctgga ggccatcgtg cagaacccca ccagcaagcc gctgacggcg cagctgttcc 8460
tggtggtgca gcatagtcgg gacaacgaag cgttcaggga ggcgctgctg aatatcaccg 8520
agcccgaggg ccgctggctc ctggacctgg tgaacattct gcagagcatc gtggtgcagg 8580
agcgcgggct gccgctgtcc gagaagctgg cggccatcaa cttctcggtg ctgagtttgg 8640
gcaagtacta cgctaggaag atctacaaga ccccgtacgt gcccatagac aaggaggtga 8700
agatcgacgg gttttacatg cgcatgaccc tgaaagtgct gaccctgagc gacgatctgg 8760
gggtgtaccg caacgacagg atgcaccgtg cggtgagcgc cagcaggcgg cgcgagctga 8820
gcgaccagga gctgatgcat agtctgcagc gggccctgac cggggccggg accgaggggg 8880
agagctactt tgacatgggc gcggacctgc actggcagcc cagccgccgg gccttggagg 8940
cggcggcagg accctacgta gaagaggtgg acgatgaggt ggacgaggag ggcgagtacc 9000
tggaagactg atggcgcgac cgtatttttg ctagatgcaa caacaacagc cacctcctga 9060
tcccgcgatg cgggcggcgc tgcagagcca gccgtccggc attaactcct cggacgattg 9120
gacccaggcc atgcaacgca tcatggcgct gacgacccgc aaccccgaag cctttagaca 9180
gcagccccag gccaaccggc tctcggccat cctggaggcc gtggtgccct cgcgctccaa 9240
ccccacgcac gagaaggtcc tggccatcgt gaacgcgctg gtggagaaca aggccatccg 9300
cggcgacgag gccggcctgg tgtacaacgc gctgctggag cgcgtggccc gctacaacag 9360
caccaacgtg cagaccaacc tggaccgcat ggtgaccgac gtgcgcgagg ccgtggccca 9420
gcgcgagcgg ttccaccgcg agtccaacct gggatccatg gtggcgctga acgccttcct 9480
cagcacccag cccgccaacg tgccccgggg ccaggaggac tacaccaact tcatcagcgc 9540
cctgcgcctg atggtgaccg aggtgcccca gagcgaggtg taccagtccg ggccggacta 9600
cttcttccag accagtcgcc agggcttgca gaccgtgaac ctgagccagg ctttcaagaa 9660
cttgcagggc ctgtggggcg tgcaggcccc ggtcggggac cgcgcgacgg tgtcgagcct 9720
gctgacgccg aactcgcgcc tgctgctgct gctggtggcc cccttcacgg acagcggcag 9780
catcaaccgc aactcgtacc tgggctacct gattaacctg taccgcgagg ccatcggcca 9840
ggcgcacgtg gacgagcaga cctaccagga gatcacccac gtgagccgcg ccctgggcca 9900
ggacgacccg ggcaacctgg aagccaccct gaactttttg ctgaccaacc ggtcgcagaa 9960
gatcccgccc cagtacgcgc tcagcaccga ggaggagcgc atcctgcgtt acgtgcagca 10020
gagcgtgggc ctgttcctga tgcaggaggg ggccaccccc agcgccgcgc tcgacatgac 10080
cgcgcgcaac atggagccca gcatgtacgc cagcaaccgc ccgttcatca ataaactgat 10140
ggactacttg catcgggcgg ccgccatgaa ctctgactat ttcaccaacg ccatcctgaa 10200
tccccactgg ctcccgccgc cggggttcta cacgggcgag tacgacatgc ccgaccccaa 10260
tgacgggttc ctgtgggacg atgtggacag cagcgtgttc tccccccgac cgggtgctaa 10320
cgagcgcccc ttgtggaaga aggaaggcag cgaccgacgc ccgtcctcgg cgctgtccgg 10380
ccgcgagggt gctgccgcgg cggtgcccga ggccgccagt cctttcccga gcttgccctt 10440
ctcgctgaac agtatccgca gcagcgagct gggcaggatc acgcgcccgc gcttgctggg 10500
cgaagaggag tacttgaatg actcgctgtt gagacccgag cgggagaaga acttccccaa 10560
taacgggata gaaagcctgg tggacaagat gagccgctgg aagacgtatg cgcaggagca 10620
cagggacgat ccccgggcgt cgcagggggc cacgagccgg ggcagcgccg cccgtaaacg 10680
ccggtggcac gacaggcagc ggggacagat gtgggacgat gaggactccg ccgacgacag 10740
cagcgtgttg gacttgggtg ggagtggtaa cccgttcgct cacctgcgcc cccgtatcgg 10800
gcgcatgatg taagagaaac cgaaaataaa tgatactcac caaggccatg gcgaccagcg 10860
tgcgttcgtt tcttctctgt tgttgttgta tctagtatga tgaggcgtgc gtacccggag 10920
ggtcctcctc cctcgtacga gagcgtgatg cagcaggcga tggcggcggc ggcgatgcag 10980
cccccgctgg aggctcctta cgtgcccccg cggtacctgg cgcctacgga ggggcggaac 11040
agcattcgtt actcggagct ggcacccttg tacgatacca cccggttgta cctggtggac 11100
aacaagtcgg cggacatcgc ctcgctgaac taccagaacg accacagcaa cttcctgacc 11160
accgtggtgc agaacaatga cttcaccccc acggaggcca gcacccagac catcaacttt 11220
gacgagcgct cgcggtgggg cggccagctg aaaaccatca tgcacaccaa catgcccaac 11280
gtgaacgagt tcatgtacag caacaagttc aaggcgcggg tgatggtctc ccgcaagacc 11340
cccaatgggg tgacagtgac agaggattat gatggtagtc aggatgagct gaagtatgaa 11400
tgggtggaat ttgagctgcc cgaaggcaac ttctcggtga ccatgaccat cgacctgatg 11460
aacaacgcca tcatcgacaa ttacttggcg gtggggcggc agaacggggt gctggagagc 11520
gacatcggcg tgaagttcga cactaggaac ttcaggctgg gctgggaccc cgtgaccgag 11580
ctggtcatgc ccggggtgta caccaacgag gctttccatc ccgatattgt cttgctgccc 11640
ggctgcgggg tggacttcac cgagagccgc ctcagcaacc tgctgggcat tcgcaagagg 11700
cagcccttcc aggaaggctt ccagatcatg tacgaggatc tggagggggg caacatcccc 11760
gcgctcctgg atgtcgacgc ctatgagaaa agcaaggagg atgcagcagc tgaagcaact 11820
gcagccgtag ctaccgcctc taccgaggtc aggggcgata attttgcaag cgccgcagca 11880
gtggcagcgg ccgaggcggc tgaaaccgaa agtaagatag tcattcagcc ggtggagaag 11940
gatagcaaga acaggagcta caacgtacta ccggacaaga taaacaccgc ctaccgcagc 12000
tggtacctag cctacaacta tggcgacccc gagaagggcg tgcgctcctg gacgctgctc 12060
accacctcgg acgtcacctg cggcgtggag caagtctact ggtcgctgcc cgacatgatg 12120
caagacccgg tcaccttccg ctccacgcgt caagttagca actacccggt ggtgggcgcc 12180
gagctcctgc ccgtctactc caagagcttc ttcaacgagc aggccgtcta ctcgcagcag 12240
ctgcgcgcct tcacctcgct tacgcacgtc ttcaaccgct tccccgagaa ccagatcctc 12300
gtccgcccgc ccgcgcccac cattaccacc gtcagtgaaa acgttcctgc tctcacagat 12360
cacgggaccc tgccgctgcg cagcagtatc cggggagtcc agcgcgtgac cgttactgac 12420
gccagacgcc gcacctgccc ctacgtctac aaggccctgg gcatagtcgc gccgcgcgtc 12480
ctctcgagcc gcaccttcta aatgtccatt ctcatctcgc ccagtaataa caccggttgg 12540
ggcctgcgcg cgcccagcaa gatgtacgga ggcgctcgcc aacgctccac gcaacacccc 12600
gtgcgcgtgc gcgggcactt ccgcgctccc tggggcgccc tcaagggccg cgtgcggtcg 12660
cgcaccaccg tcgacgacgt gatcgaccag gtggtggccg acgcgcgcaa ctacaccccc 12720
gccgccgcgc ccgtctccac cgtggacgcc gtcatcgaca gcgtggtggc ggacgcgcgc 12780
cggtacgccc gcgccaagag ccggcggcgg cgcatcgccc ggcggcaccg gagcaccccc 12840
gccatgcgcg cggcgcgagc cttgctgcgc agggccaggc gcacgggacg cagggccatg 12900
ctcagggcgg ccagacgcgc ggcttcaggc gccagcgccg gcaggacccg gagacgcgcg 12960
gccacggcgg cggcagcggc catcgccagc atgtcccgcc cgcggcgagg gaacgtgtac 13020
tgggtgcgcg acgccgccac cggtgtgcgc gtgcccgtgc gcacccgccc ccctcgcact 13080
tgaagatgtt cacttcgcga tgttgatgtg tcccagcggc gaggaggatg tccaagcgca 13140
aattcaagga agagatgctc caggtcatcg cgcctgagat ctacggccct gcggtggtga 13200
aggaggaaag aaagccccgc aaaatcaagc gggtcaaaaa ggacaaaaag gaagaagaaa 13260
gtgatgtgga cggattggtg gagtttgtgc gcgagttcgc cccccggcgg cgcgtgcagt 13320
ggcgcgggcg gaaggtgcaa ccggtgctga gacccggcac caccgtggtc ttcacgcccg 13380
gcgagcgctc cggcaccgct tccaagcgct cctacgacga ggtgtacggg gatgatgata 13440
ttctggagca ggcggccgag cgcctgggcg agtttgctta cggcaagcgc agccgttccg 13500
caccgaagga agaggcggtg tccatcccgc tggaccacgg caaccccacg ccgagcctca 13560
agcccgtgac cttgcagcag gtgctgccga ccgcggcgcc gcgccggggg ttcaagcgcg 13620
agggcgagga tctgtacccc accatgcagc tgatggtgcc caagcgccag aagctggaag 13680
acgtgctgga gaccatgaag gtggacccgg acgtgcagcc cgaggtcaag gtgcggccca 13740
tcaagcaggt ggccccgggc ctgggcgtgc agaccgtgga catcaagatt cccacggagc 13800
ccatggaaac gcagaccgag cccatgatca agcccagcac cagcaccatg gaggtgcaga 13860
cggatccctg gatgccatcg gctcctagtc gaagaccccg gcgcaagtac ggcgcggcca 13920
gcctgctgat gcccaactac gcgctgcatc cttccatcat ccccacgccg ggctaccgcg 13980
gcacgcgctt ctaccgcggt cataccagca gccgccgccg caagaccacc actcgccgcc 14040
gccgtcgccg caccgccgct gcaaccaccc ctgccgccct ggtgcggaga gtgtaccgcc 14100
gcggccgcgc acctctgacc ctgccgcgcg cgcgctacca cccgagcatc gccatttaaa 14160
ctttcgccag ctttgcagat caatggccct cacatgccgc cttcgcgttc ccattacggg 14220
ctaccgagga agaaaaccgc gccgtagaag gctggcgggg aacgggatgc gtcgccacca 14280
ccaccggcgg cggcgcgcca tcagcaagcg gttgggggga ggcttcctgc ccgcgctgat 14340
ccccatcatc gccgcggcga tcggggcgat ccccggcatt gcttccgtgg cggtgcaggc 14400
ctctcagcgc cactgagaca cacttggaaa catcttgtaa taaacccatg gactctgacg 14460
ctcctggtcc tgtgatgtgt tttcgtagac agatggaaga catcaatttt tcgtccctgg 14520
ctccgcgaca cggcacgcgg ccgttcatgg gcacctggag cgacatcggc accagccaac 14580
tgaacggggg cgccttcaat tggagcagtc tctggagcgg gcttaagaat ttcgggtcca 14640
cgcttaaaac ctatggcagc aaggcgtgga acagcaccac agggcaggcg ctgagggata 14700
agctgaaaga gcagaacttc cagcagaagg tggtcgatgg gctcgcctcg ggcatcaacg 14760
gggtggtgga cctggccaac caggccgtgc agcggcagat caacagccgc ctggacccgg 14820
tgccgcccgc cggctccgtg gagatgccgc aggtggagga ggagctgcct cccctggaca 14880
agcggggcga gaagcgaccc cgccccgatg cggaggagac gctgctgacg cacacggacg 14940
agccgccccc gtacgaggag gcggtgaaac tgggtctgcc caccacgcgg cccatcgcgc 15000
ccctggccac cggggtgctg aaacccgaaa agcccgcgac cctggacttg cctcctcccc 15060
agccttcccg cccctctaca gtggctaagc ccctgccgcc ggtggccgtg gcccgcgcgc 15120
gacccggggg caccgcccgc cctcatgcga actggcagag cactctgaac agcatcgtgg 15180
gtctgggagt gcagagtgtg aagcgccgcc gctgctatta aacctaccgt agcgcttaac 15240
ttgcttgtct gtgtgtgtat gtattatgtc gccgccgccg ctgtccacca gaaggaggag 15300
tgaagaggcg cgtcgccgag ttgcaagatg gccaccccat cgatgctgcc ccagtgggcg 15360
tacatgcaca tcgccggaca ggacgcttcg gagtacctga gtccgggtct ggtgcagttt 15420
gcccgcgcca cagacaccta cttcagtctg gggaacaagt ttaggaaccc cacggtggcg 15480
cccacgcacg atgtgaccac cgaccgcagc cagcggctga cgctgcgctt cgtgcccgtg 15540
gaccgcgagg acaacaccta ctcgtacaaa gtgcgctaca cgctggccgt gggcgacaac 15600
cgcgtgctgg acatggccag cacctacttt gacatccgcg gcgtgctgga tcggggccct 15660
agcttcaaac cctactccgg caccgcctac aacagtctgg cccccaaggg agcacccaac 15720
acttgtcagt ggacatataa agccgatggt gaaactgcca cagaaaaaac ctatacatat 15780
ggaaatgcac ccgtgcaggg cattaacatc acaaaagatg gtattcaact tggaactgac 15840
accgatgatc agccaatcta cgcagataaa acctatcagc ctgaacctca agtgggtgat 15900
gctgaatggc atgacatcac tggtactgat gaaaagtatg gaggcagagc tcttaagcct 15960
gataccaaaa tgaagccttg ttatggttct tttgccaagc ctactaataa agaaggaggt 16020
caggcaaatg tgaaaacagg aacaggcact actaaagaat atgacataga catggctttc 16080
tttgacaaca gaagtgcggc tgctgctggc ctagctccag aaattgtttt gtatactgaa 16140
aatgtggatt tggaaactcc agatacccat attgtataca aagcaggcac agatgacagc 16200
agctcttcta ttaatttggg tcagcaagcc atgcccaaca gacctaacta cattggtttc 16260
agagacaact ttatcgggct catgtactac aacagcactg gcaatatggg ggtgctggcc 16320
ggtcaggctt ctcagctgaa tgctgtggtt gacttgcaag acagaaacac cgagctgtcc 16380
taccagctct tgcttgactc tctgggtgac agaacccggt atttcagtat gtggaatcag 16440
gcggtggaca gctatgatcc tgatgtgcgc attattgaaa atcatggtgt ggaggatgaa 16500
cttcccaact attgtttccc tctggatgct gttggcagaa cagatactta tcagggaatt 16560
aaggctaatg gaactgatca aaccacatgg accaaagatg acagtgtcaa tgatgctaat 16620
gagataggca agggtaatcc attcgccatg gaaatcaaca tccaagccaa cctgtggagg 16680
aacttcctct acgccaacgt ggccctgtac ctgcccgact cttacaagta cacgccggcc 16740
aatgttaccc tgcccaccaa caccaacacc tacgattaca tgaacggccg ggtggtggcg 16800
ccctcgctgg tggactccta catcaacatc ggggcgcgct ggtcgctgga tcccatggac 16860
aacgtgaacc ccttcaacca ccaccgcaat gcggggctgc gctaccgctc catgctcctg 16920
ggcaacgggc gctacgtgcc cttccacatc caggtgcccc agaaattttt cgccatcaag 16980
agcctcctgc tcctgcccgg gtcctacacc tacgagtgga acttccgcaa ggacgtcaac 17040
atgatcctgc agagctccct cggcaacgac ctgcgcacgg acggggcctc catctccttc 17100
accagcatca acctctacgc caccttcttc cccatggcgc acaacacggc ctccacgctc 17160
gaggccatgc tgcgcaacga caccaacgac cagtccttca acgactacct ctcggcggcc 17220
aacatgctct accccatccc ggccaacgcc accaacgtgc ccatctccat cccctcgcgc 17280
aactgggccg ccttccgcgg ctggtccttc acgcgtctca agaccaagga gacgccctcg 17340
ctgggctccg ggttcgaccc ctacttcgtc tactcgggct ccatccccta cctcgacggc 17400
accttctacc tcaaccacac cttcaagaag gtctccatca ccttcgactc ctccgtcagc 17460
tggcccggca acgaccggct cctgacgccc aacgagttcg aaatcaagcg caccgtcgac 17520
ggcgagggct acaacgtggc ccagtgcaac atgaccaagg actggttcct ggtccagatg 17580
ctggcccact acaacatcgg ctaccagggc ttctacgtgc ccgagggcta caaggaccgc 17640
atgtactcct tcttccgcaa cttccagccc atgagccgcc aggtggtgga cgaggtcaac 17700
tacaaggact accaggccgt caccctggcc taccagcaca acaactcggg cttcgtcggc 17760
tacctcgcgc ccaccatgcg ccagggccag ccctaccccg ccaactaccc ctacccgctc 17820
atcggcaaga gcgccgtcac cagcgtcacc cagaaaaagt tcctctgcga cagggtcatg 17880
tggcgcatcc ccttctccag caacttcatg tccatgggcg cgctcaccga cctcggccag 17940
aacatgctct atgccaactc cgcccacgcg ctagacatga atttcgaagt cgaccccatg 18000
gatgagtcca cccttctcta tgttgtcttc gaagtcttcg acgtcgtccg agtgcaccag 18060
ccccaccgcg gcgtcatcga ggccgtctac ctgcgcaccc ccttctcggc cggtaacgcc 18120
accacctaag ctcttgcttc ttgcaagcca tggccgcggg ctccggcgag caggagctca 18180
gggccatcat ccgcgacctg ggctgcgggc cctacttcct gggcaccttc gataagcgct 18240
tcccgggatt catggccccg cacaagctgg cctgcgccat cgtcaacacg gccggccgcg 18300
agaccggggg cgagcactgg ctggccttcg cctggaaccc gcgctcgaac acctgctacc 18360
tcttcgaccc cttcgggttc tcggacgagc gcctcaagca gatctaccag ttcgagtacg 18420
agggcctgct gcgccgcagc gccctggcca ccgaggaccg ctgcgtcacc ctggaaaagt 18480
ccacccagac cgtgcagggt ccgcgctcgg ccgcctgcgg gctcttctgc tgcatgttcc 18540
tgcacgcctt cgtgcactgg cccgaccgcc ccatggacaa gaaccccacc atgaacttgc 18600
tgacgggggt gcccaacggc atgctccagt cgccccaggt ggaacccacc ctgcgccgca 18660
accaggaggc gctctaccgc ttcctcaact cccactccgc ctactttcgc tcccaccgcg 18720
cgcgcatcga gaaggccacc gccttcgacc gcatgaatca agacatgtaa accgtgtgtg 18780
tatgttaaat gtctttaata aacagcactt tcatgttaca catgcatctg agatgattta 18840
tttagaaatc gaaagggttc tgccgggtct cggcatggcc cgcgggcagg gacacgttgc 18900
ggaactggta cttggccagc cacttgaact cggggatcag cagtttgggc agcggggtgt 18960
cggggaagga gtcggtccac agcttccgcg tcagttgcag ggcgcccagc aggtcgggcg 19020
cggagatctt gaaatcgcag ttgggacccg cgttctgcgc gcgggagttg cggtacacgg 19080
ggttgcagca ctggaacacc atcagggccg ggtgcttcac gctcgccagc accgtcgcgt 19140
cggtgatgct ctccacgtcg aggtcctcgg cgttggccat cccgaagggg gtcatcttgc 19200
aggtctgcct tcccatggtg ggcacgcacc cgggcttgtg gttgcaatcg cagtgcaggg 19260
ggatcagcat catctgggcc tggtcggcgt tcatccccgg gtacatggcc ttcatgaaag 19320
cctccaattg cctgaacgcc tgctgggcct tggctccctc ggtgaagaag accccgcagg 19380
acttgctaga gaactggttg gtggcgcacc cggcgtcgtg cacgcagcag cgcgcgtcgt 19440
tgttggccag ctgcaccacg ctgcgccccc agcggttctg ggtgatcttg gcccggtcgg 19500
ggttctcctt cagcgcgcgc tgcccgttct cgctcgccac atccatctcg atcatgtgct 19560
ccttctggat catggtggtc ccgtgcaggc accgcagctt gccctcggcc tcggtgcacc 19620
cgtgcagcca cagcgcgcac ccggtgcact cccagttctt gtgggcgatc tgggaatgcg 19680
cgtgcacgaa gccctgcagg aagcggccca tcatggtggt cagggtcttg ttgctagtga 19740
aggtcagcgg aatgccgcgg tgctcctcgt tgatgtacag gtggcagatg cggcggtaca 19800
cctcgccctg ctcgggcatc agctggaagt tggctttcag gtcggtctcc acgcggtagc 19860
ggtccatcag catagtcatg atttccatac ccttctccca ggccgagacg atgggcaggc 19920
tcatagggtt cttcaccatc atcttagcgc tagcagccgc ggccaggggg tcgctctcgt 19980
ccagggtctc aaagctccgc ttgccgtcct tctcggtgat ccgcaccggg gggtagctga 20040
agcccacggc cgccagctcc tcctcggcct gtctttcgtc ctcgctgtcc tggctgacgt 20100
cctgcaggac cacatgcttg gtcttgcggg gtttcttctt gggcggcagc ggcggcggag 20160
atgttggaga tggcgagggg gagcgcgagt tctcgctcac cactactatc tcttcctctt 20220
cttggtccga ggccacgcgg cggtaggtat gtctcttcgg gggcagaggc ggaggcgacg 20280
ggctctcgcc gccgcgactt ggcggatggc tggcagagcc ccttccgcgt tcgggggtgc 20340
gctcccggcg gcgctctgac tgacttcctc cgcggccggc cattgtgttc tcctagggag 20400
gaacaacaag catggagact cagccatcgc caacctcgcc atctgccccc accgccgacg 20460
agaagcagca gcagcagaat gaaagcttaa ccgccccgcc gcccagcccc gccacctccg 20520
acgcggccgt cccagacatg caagagatgg aggaatccat cgagattgac ctgggctatg 20580
tgacgcccgc ggagcacgag gaggagctgg cagtgcgctt ttcacaagaa gagatacacc 20640
aagaacagcc agagcaggaa gcagagaatg agcagagtca ggctgggctc gagcatgacg 20700
gcgactacct ccacctgagc gggggggagg acgcgctcat caagcatctg gcccggcagg 20760
ccaccatcgt caaggatgcg ctgctcgacc gcaccgaggt gcccctcagc gtggaggagc 20820
tcagccgcgc ctacgagttg aacctcttct cgccgcgcgt gccccccaag cgccagccca 20880
atggcacctg cgagcccaac ccgcgcctca acttctaccc ggtcttcgcg gtgcccgagg 20940
ccctggccac ctaccacatc tttttcaaga accaaaagat ccccgtctcc tgccgcgcca 21000
accgcacccg cgccgacgcc cttttcaacc tgggtcccgg cgcccgccta cctgatatcg 21060
cctccttgga agaggttccc aagatcttcg agggtctggg cagcgacgag actcgggccg 21120
cgaacgctct gcaaggagaa ggaggagagc atgagcacca cagcgccctg gtcgagttgg 21180
aaggcgacaa cgcgcggctg gcggtgctca aacgcacggt cgagctgacc catttcgcct 21240
acccggctct gaacctgccc cccaaagtca tgagcgcggt catggaccag gtgctcatca 21300
agcgcgcgtc gcccatctcc gaggacgagg gcatgcaaga ctccgaggag ggcaagcccg 21360
tggtcagcga cgagcagctg gcccggtggc tgggtcctaa tgctagtccc cagagtttgg 21420
aagagcggcg caaactcatg atggccgtgg tcctggtgac cgtggagctg gagtgcctgc 21480
gccgcttctt cgccgacgcg gagaccctgc gcaaggtcga ggagaacctg cactacctct 21540
tcaggcacgg gttcgtgcgc caggcctgca agatctccaa cgtggagctg accaacctgg 21600
tctcctacat gggcatcttg cacgagaacc gcctggggca gaacgtgctg cacaccaccc 21660
tgcgcgggga ggcccggcgc gactacatcc gcgactgcgt ctacctctac ctctgccaca 21720
cctggcagac gggcatgggc gtgtggcagc agtgtctgga ggagcagaac ctgaaagagc 21780
tctgcaagct cctgcagaag aacctcaagg gtctgtggac cgggttcgac gagcgcacca 21840
ccgcctcgga cctggccgac ctcattttcc ccgagcgcct caggctgacg ctgcgcaacg 21900
gcctgcccga ctttatgagc caaagcatgt tgcaaaactt tcgctctttc atcctcgaac 21960
gctccggaat cctgcccgcc acctgctccg cgctgccctc ggacttcgtg ccgctgacct 22020
tccgcgagtg ccccccgccg ctgtggagcc actgctacct gctgcgcctg gccaactacc 22080
tggcctacca ctcggacgtg atcgaggacg tcagcggcga gggcctgctc gagtgccact 22140
gccgctgcaa cctctgcacg ccgcaccgct ccctggcctg caacccccag ctgctgagcg 22200
agacccagat catcggcacc ttcgagttgc aagggcccag cgaaggcgag ggttcagccg 22260
ccaagggggg tctgaaactc accccggggc tgtggacctc ggcctacttg cgcaagttcg 22320
tgcccgagga ctaccatccc ttcgagatca ggttctacga ggaccaatcc catccgccca 22380
aggccgagct gtcggcctgc gtcatcaccc agggggcgat cctggcccaa ttgcaagcca 22440
tccagaaatc ccgccaagaa ttcttgctga aaaagggccg cggggtctac ctcgaccccc 22500
agaccggtga ggagctcaac cccggcttcc cccaggatgc cccgaggaaa caagaagctg 22560
aaagtggagc tgccgcccgt ggaggatttg gaggaagact gggagaacag cagtcaggca 22620
gaggaggagg agatggagga agactgggac agcactcagg cagaggagga cagcctgcaa 22680
gacagtctgg aggaagacga ggaggaggca gaggaggagg tggaagaagc agccgccgcc 22740
agaccgtcgt cctcggcggg ggagaaagca agcagcacgg ataccatctc cgctccgggt 22800
cggggtcccg ctcgaccaca cagtagatgg gacgagaccg gacgattccc gaaccccacc 22860
acccagaccg gtaagaagga gcggcaggga tacaagtcct ggcgggggca caaaaacgcc 22920
atcgtctcct gcttgcaggc ctgcgggggc aacatctcct tcacccggcg ctacctgctc 22980
ttccaccgcg gggtgaactt tccccgcaac atcttgcatt actaccgtca cctccacagc 23040
ccctactact tccaagaaga ggcagcagca gcagaaaaag accagcagaa aaccagcagc 23100
tagaaaatcc acagcggcgg cagcaggtgg actgaggatc gcggcgaacg agccggcgca 23160
aacccgggag ctgaggaacc ggatctttcc caccctctat gccatcttcc agcagagtcg 23220
ggggcaggag caggaactga aagtcaagaa ccgttctctg cgctcgctca cccgcagttg 23280
tctgtatcac aagagcgaag accaacttca gcgcactctc gaggacgccg aggctctctt 23340
caacaagtac tgcgcgctca ctcttaaaga gtagcccgcg cccgcccagt cgcagaaaaa 23400
ggcgggaatt acgtcacctg tgcccttcgc cctagccgcc tccacccatc atcatgagca 23460
aagagattcc cacgccttac atgtggagct accagcccca gatgggcctg gccgccggtg 23520
ccgcccagga ctactccacc cgcatgaatt ggctcagcgc cgggcccgcg atgatctcac 23580
gggtgaatga catccgcgcc caccgaaacc agatactcct agaacagtca gcgctcaccg 23640
ccacgccccg caatcacctc aatccgcgta attggcccgc cgccctggtg taccaggaaa 23700
ttccccagcc cacgaccgta ctacttccgc gagacgccca ggccgaagtc cagctgacta 23760
actcaggtgt ccagctggcg ggcggcgcca ccctgtgtcg tcaccgcccc gctcagggta 23820
taaagcggct ggtgatccgg ggcagaggca cacagctcaa cgacgaggtg gtgagctctt 23880
cgctgggtct gcgacctgac ggagtcttcc aactcgccgg atcggggaga tcttccttca 23940
cgcctcgtca ggccgtcctg actttggaga gttcgtcctc gcagccccgc tcgggtggca 24000
tcggcactct ccagttcgtg gaggagttca ctccctcggt ctacttcaac cccttctccg 24060
gctcccccgg ccactacccg gacgagttca tcccgaactt cgacgccatc agcgagtcgg 24120
tggacggcta cgattgagtt taaactcacc cccttatcca gtgaaataaa gatcatattg 24180
atgatgattt tacagaaata aaaaataatc atttgatttg aaataaagat acaatcatat 24240
tgatgatttg agtttaacaa aaaaataaag aatcacttac ttgaaatctg ataccaggtc 24300
tctgtccatg ttttctgcca acaccacttc actcccctct tcccagctct ggtactgcag 24360
gccccggcgg gctgcaaact tcctccacac gctgaagggg atgtcaaatt cctcctgtcc 24420
ctcaatcttc attttatctt ctatcagatg tccaaaaagc gcgtccgggt ggatgatgac 24480
ttcgaccccg tctaccccta cgatgcagac aacgcaccga ccgtgccctt catcaacccc 24540
cccttcgtct cttcagatgg attccaagag aagcccctgg gggtgttgtc cctgcgactg 24600
gccgaccccg tcaccaccaa gaacggggaa atcaccctca agctgggaga gggggtggac 24660
ctcgattcct cgggaaaact catctccaac acggccacca aggccgccgc ccctctcagt 24720
ttttccaaca acaccatttc ccttaacatg gatcacccct tttacactaa agatggaaaa 24780
ttatccttac aagtttctcc accattaaat atactgagaa caagcattct aaacacacta 24840
gctttaggtt ttggatcagg tttaggactc cgtggctctg ccttggcagt acagttagtc 24900
tctccactta catttgatac tgatggaaac ataaagctta ccttagacag aggtttgcat 24960
gttacaacag gagatgcaat tgaaagcaac ataagctggg ctaaaggttt aaaatttgaa 25020
gatggagcca tagcaaccaa cattggaaat gggttagagt ttggaagcag tagtacagaa 25080
acaggtgttg atgatgctta cccaatccaa gttaaacttg gatctggcct tagctttgac 25140
agtacaggag ccataatggc tggtaacaaa gaagacgata aactcacttt gtggacaaca 25200
cctgatccat caccaaactg tcaaatactc gcagaaaatg atgcaaaact aacactttgc 25260
ttgactaaat gtggtagtca aatactggcc actgtgtcag tcttagttgt aggaagtgga 25320
aacctaaacc ccattactgg caccgtaagc agtgctcagg tgtttctacg ttttgatgca 25380
aacggtgttc ttttaacaga acattctaca ctaaaaaaat actgggggta taggcaggga 25440
gatagcatag atggcactcc atataccaat gctgtaggat tcatgcccaa tttaaaagct 25500
tatccaaagt cacaaagttc tactactaaa aataatatag tagggcaagt atacatgaat 25560
ggagatgttt caaaacctat gcttctcact ataaccctca atggtactga tgacagcaac 25620
agtacatatt caatgtcatt ttcatacacc tggactaatg gaagctatgt tggagcaaca 25680
tttggggcta actcttatac cttctcatac atcgcccaag aatgaacact gtatcccacc 25740
ctgcatgcca acccttccca ccccactctg tggaacaaac tctgaaacac aaaataaaat 25800
aaagttcaag tgttttattg attcaacagt ttcacagaac cctagtattc aacctgccac 25860
ctccctccca acacacagag tacacagtcc tttctccccg gctggcctta aaaagcatca 25920
tatcatgggt aacagacata ttcttaggtg ttatattcca cacggtttcc tgtcgagcca 25980
aacgctcatc agtgatatta ataaactccc cgggcagctc acttaagttc atgtcgctgt 26040
ccagctgctg agccacaggc tgctgtccaa cttgcggttg cttaacgggc ggcgaaggag 26100
aagtccacgc ctacatgggg gtagagtcat aatcgtgcat caggataggg cggtggtgct 26160
gcagcagcgc gcgaataaac tgctgccgcc gccgctccgt cctgcaggaa tacaacatgg 26220
cagtggtctc ctcagcgatg attcgcaccg cccgcagcat aaggcgcctt gtcctccggg 26280
cacagcagcg caccctgatc tcacttaaat cagcacagta actgcagcac agcaccacaa 26340
tattgttcaa aatcccacag tgcaaggcgc tgtatccaaa gctcatggcg gggaccacag 26400
aacccacgtg gccatcatac cacaagcgca ggtagattaa gtggcgaccc ctcataaaca 26460
cgctggacat aaacattacc tcttttggca tgttgtaatt caccacctcc cggtaccata 26520
taaacctctg attaaacatg gcgccatcca ccaccatcct aaaccagctg gccaaaacct 26580
gcccgccggc tatacactgc agggaaccgg gactggaaca atgacagtgg agagcccagg 26640
actcgtaacc atggatcatc atgctcgtca tgatatcaat gttggcacaa cacaggcaca 26700
cgtgcataca cttcctcagg attacaagct cctcccgcgt tagaaccata tcccagggaa 26760
caacccattc ctgaatcagc gtaaatccca cactgcaggg aagacctcgc acgtaactca 26820
cgttgtgcat tgtcaaagtg ttacattcgg gcagcagcgg atgatcctcc agtatggtag 26880
cgcgggtttc tgtctcaaaa ggaggtagac gatccctact gtacggagtg cgccgagaca 26940
accgagatcg tgttggtcgt agtgtcatgc caaatggaac gccggacgta gtcatatttc 27000
ctgaagcaaa accaggtgcg ggcgtgacaa acagatctgc gtctccggtc tcgccgctta 27060
gatcgctctg tgtagtagtt gtagtatatc cactctctca aagcatccag gcgccccctg 27120
gcttcgggtt ctatgtaaac tccttcatgc gccgctgccc tgataacatc caccaccgca 27180
gaataagcca cacccagcca acctacacat tcgttctgcg agtcacacac gggaggagcg 27240
ggaagagctg gaagaaccat gattaacttt attccaaacg gtctcggagc acttcaaaat 27300
gcaggtcccg gaggtggcac ctctcgcccc cactgtgttg gtggaaaata acagccaggt 27360
caaaggtgac acggttctcg agatgttcca cggtggcttc cagcaaagcc tccacgcgca 27420
catccagaaa caagaggaca gcgaaagcgg gagcgttttc taattcctca atcatcatat 27480
tacactcctg caccatcccc agataatttt catttttcca gccttgaatg attcgtatta 27540
gttcctgagg taaatccaag ccagccatga taaaaagctc gcgcagagcg ccctccaccg 27600
gcattcttaa gcacaccctc ataattccaa gagattctgc tcctggttca cctgcagcag 27660
attaacaatg ggaatatcaa aatctctgcc gcgatcccta agctcctccc tcaacaataa 27720
ctgtatgtaa tctttcatat catctccgaa atttttagcc atagggccgc caggaataag 27780
agcagggcaa gccacattac agataaagcg aagtcctccc cagtgwgcat tgccaaatgt 27840
aagattgaaa taagcatgct ggctagaccc tgtgatatct tccagataac tggacagaaa 27900
atcaggcaag caatttttaa gaaaatcaac aaaagaaaag tcgtccaggt gcaggtttag 27960
agcctcagga acaacgatgg aataagtgca aggagtgcgt tccagcatgg ttagtgtttt 28020
tttggtgatc tgtagaacaa aaaataaaca tgcaatatta aaccatgcta gcctggcgaa 28080
caggtgggta aatcactctt tccagcacca ggcaggctac ggggtctccg gcgcgaccct 28140
cgtagaagct gtcgccatga ttgaaaagca tcaccgagag accttcccgg tggccggcat 28200
ggatgattcg agaagaagca tacactccgg gaacattggc atccgtgagt gaaaaaaagc 28260
gacctataaa gcctcggggc actacaatgc tcaatctcaa ttccagcaaa gccaccccat 28320
gcggatggag cacaaaattg gcaggtgcgt aaaaaatgta attactcccc tcctgcacag 28380
gcagcaaagc ccccgctccc tccagaaaca catacaaagc ctcagcgtcc atagcttacc 28440
gagcacggca ggcgcaagag tcagagaaaa ggctgagctc taacctgact gcccgctcct 28500
gtgctcaata tatagcccta acctacactg acgtaaaggc caaagtctaa aaatacccgc 28560
caaataatca cacacgccca gcacacgccc agaaaccggt gacacactca aaaaaatacg 28620
cgcacttcct caaacgccca aaactgccgt catttccggg ttcccacgct acgtcatcaa 28680
aacacgactt tcaaattccg tcgaccgtta aaaacgtcac ccgccccgcc cctaacggtc 28740
gcccgtctct cagccaatca gcgccccgca tccccaaatt caaacacctc atttgcatat 28800
taacgcgcac aaaaagtttg aggtatatta ttgatgatgg ttaattaagg atccttctat 28860
agtgtcacct aaatgtcgac ggccaggcgg ccgccaggcc tacccactag tcaattcggg 28920
aggatcgaaa cggcagatcg caaaaaacag tacatacaga aggagacatg aacatgaaca 28980
tcaaaaaaat tgtaaaacaa gccacagttc tgacttttac gactgcactt ctggcaggag 29040
gagcgactca agccttcgcg aaagaaaata accaaaaagc atacaaagaa acgtacggcg 29100
tctctcatat tacacgccat gatatgctgc agatccctaa acagcagcaa aacgaaaaat 29160
accaagtgcc tcaattcgat caatcaacga ttaaaaatat tgagtctgca aaaggacttg 29220
atgtgtggga cagctggccg ctgcaaaacg ctgacggaac agtagctgaa tacaacggct 29280
atcacgttgt gtttgctctt gcgggaagcc cgaaagacgc tgatgacaca tcaatctaca 29340
tgttttatca aaaggtcggc gacaactcaa tcgacagctg gaaaaacgcg ggccgtgtct 29400
ttaaagacag cgataagttc gacgccaacg atccgatcct gaaagatcag acgcaagaat 29460
ggtccggttc tgcaaccttt acatctgacg gaaaaatccg tttattctac actgactatt 29520
ccggtaaaca ttacggcaaa caaagcctga caacagcgca ggtaaatgtg tcaaaatctg 29580
atgacacact caaaatcaac ggagtggaag atcacaaaac gatttttgac ggagacggaa 29640
aaacatatca gaacgttcag cagtttatcg atgaaggcaa ttatacatcc ggcgacaacc 29700
atacgctgag agaccctcac tacgttgaag acaaaggcca taaatacctt gtattcgaag 29760
ccaacacggg aacagaaaac ggataccaag gcgaagaatc tttatttaac aaagcgtact 29820
acggcggcgg cacgaacttc ttccgtaaag aaagccagaa gcttcagcag agcgctaaaa 29880
aacgcgatgc tgagttagcg aacggcgccc tcggtatcat agagttaaat aatgattaca 29940
cattgaaaaa agtaatgaag ccgctgatca cttcaaacac ggtaactgat gaaatcgagc 30000
gcgcgaatgt tttcaaaatg aacggcaaat ggtacttgtt cactgattca cgcggttcaa 30060
aaatgacgat cgatggtatt aactcaaacg atatttacat gcttggttat gtatcaaact 30120
ctttaaccgg cccttacaag ccgctgaaca aaacagggct tgtgctgcaa atgggtcttg 30180
atccaaacga tgtgacattc acttactctc acttcgcagt gccgcaagcc aaaggcaaca 30240
atgtggttat cacaagctac atgacaaaca gaggcttctt cgaggataaa aaggcaacat 30300
ttgcgccaag cttcttaatg aacatcaaag gcaataaaac atccgttgtc aaaaacagca 30360
tcctggagca aggacagctg acagtcaact aataacagca aaaagaaaat gccgatactt 30420
cattggcatt ttcttttatt tctcaacaag atggtgaatt gactagtggg tagatccaca 30480
ggacgggtgt ggtcgccatg atcgcgtagt cgatagtggc tccaagtagc gaagcgagca 30540
ggactgggcg gcggccaaag cggtcggaca gtgctccgag aacgggtgcg catagaaatt 30600
gcatcaacgc atatagcgct agcagcacgc catagtgact ggcgatgctg tcggaatgga 30660
cgatatcccg caagaggccc ggcagtaccg gcataaccaa gcctatgcct acagcatcca 30720
gggtgacggt gccgaggatg acgatgagcg cattgttaga tttcatacac ggtgcctgac 30780
tgcgttagca atttaactgt gataaactac cgcattaaag cttatcgatg ataagctgtc 30840
aaacatgaga attgatccgg aacccttaat ataacttcgt ataatgtatg ctatacgaag 30900
ttattaggtc cctcgactat agggtcaccg tcgacagcga cacacttgca tcggatgcag 30960
cccggttaac gtgccggcac ggcctgggta accaggtatt ttgtccacat aaccgtgcgc 31020
aaaatgttgt ggataagcag gacacagcag caatccacag caggcataca accgcacacc 31080
gaggttactc cgttctacag gttacgacga catgtcaata cttgcccttg acaggcattg 31140
atggaatcgt agtctcacgc tgatagtctg atcgacaata caagtgggac cgtggtccca 31200
gaccgataat cagaccgaca acacgagtgg gatcgtggtc ccagactaat aatcagaccg 31260
acgatacgag tgggaccgtg gtcccagact aataatcaga ccgacgatac gagtgggacc 31320
gtggttccag actaataatc agaccgacga tacgagtggg accgtggtcc cagactaata 31380
atcagaccga cgatacgagt gggaccatgg tcccagacta ataatcagac cgacgatacg 31440
agtgggaccg tggtcccagt ctgattatca gaccgacgat acgagtggga ccgtggtccc 31500
agactaataa tcagaccgac gatacgagtg ggaccgtggt cccagactaa taatcagacc 31560
gacgatacga gtgggaccgt ggtcccagtc tgattatcag accgacgata caagtggaac 31620
agtgggccca gagagaatat tcaggccagt tatgctttct ggcctgtaac aaaggacatt 31680
aagtaaagac agataaacgt agactaaaac gtggtcgcat cagggtgctg gcttttcaag 31740
ttccttaaga atggcctcaa ttttctctat acactcagtt ggaacacgag acctgtccag 31800
gttaagcacc attttatcgc ccttatacaa tactgtcgct ccaggagcaa actgatgtcg 31860
tgagcttaaa ctagttcttg atgcagatga cgttttaagc acagaagtta aaagagtgat 31920
aacttcttca gcttcaaata tcaccccagc ttttttctgc tcatgaaggt tagatgcctg 31980
ctgcttaagt aattcctctt tatctgtaaa ggctttttga agtgcatcac ctgaccgggc 32040
agatagttca ccggggtgag aaaaaagagc aacaactgat ttaggcaatt tggcggtgtt 32100
gatacagcgg gtaataatct tacgtgaaat attttccgca tcagccagcg cagaaatatt 32160
tccagcaaat tcattctgca atcggcttgc ataacgctga ccacgttcat aagcacttgt 32220
tgggcgataa tcgttaccca atctggataa tgcagccatc tgctcatcat ccagctcgcc 32280
aaccagaaca cgataatcac tttcggtaag tgcagcagct ttacgacggc gactcccatc 32340
ggcaatttct atgacaccag atactcttcg accgaacgcc ggtgtctgtt gaccagtcag 32400
tagaaaagaa gggatgagat catccagtgc gtcctcagta agcagctcct ggtcacgttc 32460
attacctgac catacccgag aggtcttctc aacactatca ccccggagca cttcaagagt 32520
aaacttcaca tcccgaccac atacaggcaa agtaatggca ttaccgcgag ccattactcc 32580
tacgcgcgca attaacgaat ccaccatcgg ggcagctggt gtcgataacg aagtatcttc 32640
aaccggttga gtattgagcg tatgttttgg aataacaggc gcacgcttca ttatctaatc 32700
tcccagcgtg gtttaatcag acgatcgaaa atttcattgc agacaggttc ccaaatagaa 32760
agagcatttc tccaggcacc agttgaagag cgttgatcaa tggcctgttc aaaaacagtt 32820
ctcatccgga tctgaccttt accaacttca tccgtttcac gtacaacatt ttttagaacc 32880
atgcttcccc aggcatcccg aatttgctcc tccatccacg gggactgaga gccattacta 32940
ttgctgtatt tggtaagcaa aatacgtaca tcaggctcga accctttaag atcaacgttc 33000
ttgagcagat cacgaagcat atcgaaaaac tgcagtgcgg aggtgtagtc aaacaactca 33060
gcaggcgtgg gaacaatcag cacatcagca gcacatacga cattaatcgt gccgataccc 33120
aggttaggcg cgctgtcaat aactatgaca tcatagtcat gagcaacagt ttcaatggcc 33180
agtcggagca tcaggtgtgg atcggtgggc agtttacctt catcaaattt gcccattaac 33240
tcagtttcaa tacggtgcag agccagacag gaaggaataa tgtcaagccc cggccagcaa 33300
gtgggcttta ttgcataagt gacatcgtcc ttttccccaa gatagaaagg caggagagtg 33360
tcttctgcat gaatatgaag atctggtacc catccgtgat acattgaggc tgttccctgg 33420
gggtcgttac cttccacgag caaaacacgt agccccttca gagccagatc ctgagcaaga 33480
tgaacagaaa ctgaggtttt gtaaacgcca cctttatggg cagcaacccc gatcaccggt 33540
ggaaatacgt cttcagcacg tcgcaatcgc gtaccaaaca catcacgcat atgattaatt 33600
tgttcaattg tataaccaac acgttgctca acccgtcctc gaatttccat atccgggtgc 33660
ggtagtcgcc ctgctttctc ggcatctctg atagcctgag aagaaacccc aactaaatcc 33720
gctgcttcac ctattctcca gcgccgggtt attttcctcg cttccgggct gtcatcatta 33780
aactgtgcaa tggcgatagc cttcgtcatt tcatgaccag cgtttatgca ctggttaagt 33840
gtttccatga gtttcattct gaacatcctt taatcattgc tttgcgtttt tttattaaat 33900
cttgcaattt actgcaaagc aacaacaaaa tcgcaaagtc atcaaaaaac cgcaaagttg 33960
tttaaaataa gagcaacact acaaaaggag ataagaagag cacatacctc agtcacttat 34020
tatcactagc gctcgccgca gccgtgtaac cgagcatagc gagcgaactg gcgaggaagc 34080
aaagaagaac tgttctgtca gatagctctt acgctcagcg caagaagaaa tatccaccgt 34140
gggaaaaact ccaggtagag gtacacacgc ggatagccaa ttcagagtaa taaactgtga 34200
taatcaaccc tcatcaatga tgacgaacta acccccgata tcaggtcaca tgacgaaggg 34260
aaagagaagg aaatcaactg tgacaaactg ccctcaaatt tggcttcctt aaaaattaca 34320
gttcaaaaag tatgagaaaa tccatgcagg ctgaaggaaa cagcaaaact gtgacaaatt 34380
accctcagta ggtcagaaca aatgtgacga accaccctca aatctgtgac agataaccct 34440
cagactatcc tgtcgtcatg gaagtgatat cgcggaagga aaatacgata tgagtcgtct 34500
ggcggccttt ctttttctca atgtatgaga ggcgcattgg agttctgctg ttgatctcat 34560
taacacagac ctgcaggaag cggcggcgga agtcaggcat acgctggtaa ctttgaggca 34620
gctggtaacg ctctatgatc cagtcgattt tcagagagac gatgcctgag ccatccggct 34680
tacgatactg acacagggat tcgtataaac gcatggcata cggattggtg atttcttttg 34740
tttcactaag ccgaaactgc gtaaaccggt tctgtaaccc gataaagaag ggaatgagat 34800
atgggttgat atgtacactg taaagccctc tggatggact gtgcgcacgt ttgataaacc 34860
aaggaaaaga ttcatagcct ttttcatcgc cggcatcctc ttcagggcga taaaaaacca 34920
cttccttccc cgcgaaactc ttcaatgcct gccgtatatc cttactggct tccgcagagg 34980
tcaatccgaa tatttcagca tatttagcaa catggatctc gcagataccg tcatgttcct 35040
gtagggtgcc atcagatttt ctgatctggt caacgaacag atacagcata cgtttttgat 35100
cccgggagag actatatgcc gcctcagtga ggtcgtttga ctggacgatt cgcgggctat 35160
ttttacgttt cttgtgattg ataaccgctg tttccgccat gacagatcca tgtgaagtgt 35220
gacaagtttt tagattgtca cactaaataa aaaagagtca ataagcaggg ataactttgt 35280
gaaaaaacag cttcttctga gggcaatttg tcacagggtt aagggcaatt tgtcacagac 35340
aggactgtca tttgagggtg atttgtcaca ctgaaagggc aatttgtcac aacaccttct 35400
ctagaaccag catggataaa ggcctacaag gcgctctaaa aaagaagatc taaaaactat 35460
aaaaaaaata attataaaaa tatccccgtg gataagtgga taaccccaag ggaagttttt 35520
tcaggcatcg tgtgtaagca gaatatataa gtgctgttcc ctggtgcttc ctcgctcact 35580
cgagggcttc gccctgtcgc tcaactgcgg cgagcactac tggctgtaaa aggacagacc 35640
acatcatggt tctgtgttca ttaggttgtt ctgtccattg ctgacataat ccgctccact 35700
tcaacgtaac accgcacgaa gatttctatt gttcctgaag gcatattcaa atcgttttcg 35760
ttaccgcttg caggcatcat gacagaacac tacttcctat aaacgctaca caggctcctg 35820
agattaataa tgcggatctc tacgataatg ggagattttc ccgactgttt cgttcgcttc 35880
tcagtggata acagccagct tctctgttta acagacaaaa acagcatatc cactcagttc 35940
cacatttcca tataaaggcc aaggcattta ttctcaggat aattgtttca gcatcgcaac 36000
cgcatcagac tccggcatcg caaactgcac ccggtgccgg gcagccacat ccagcgcaaa 36060
aaccttcgtg tagacttccg ttgaactgat ggacttatgt cccatcaggc tttgcagaac 36120
tttcagcggt ataccggcat acagcatgtg catcgcatag gaatggcgga acgtatgtgg 36180
tgtgaccgga acagagaacg tcacaccgtc agcagcagcg gcggcaaccg cctccccaat 36240
ccaggtcctg accgttctgt ccgtcacttc ccagatccgc gctttctctg tccttcctgt 36300
gcgacggtta cgccgctcca tgagcttatc gcgaataaat acctgtgacg gaagatcact 36360
tcgcagaata aataaatcct ggtgtccctg ttgataccgg gaagccctgg gccaactttt 36420
ggcgaaaatg agacgttgat cggcacgtaa gaggttccaa ctttcaccat aatgaaataa 36480
gatcactacc gggcgtattt tttgagttat cgagattttc aggagctaag gaagctaaaa 36540
tggagaaaaa aatcactgga tataccaccg ttgatatatc ccaatggcat cgtaaagaac 36600
attttgaggc atttcagtca gttgctcaat gtacctataa ccagaccgtt cagctggata 36660
ttacggcctt tttaaagacc gtaaagaaaa ataagcacaa gttttatccg gcctttattc 36720
acattcttgc ccgcctgatg aatgctcatc cggagttccg tatggcaatg aaagacggtg 36780
agctggtgat atgggatagt gttcaccctt gttacaccgt tttccatgag caaactgaaa 36840
cgttttcatc gctctggagt gaataccacg acgatttccg gcagtttcta cacatatatt 36900
cgcaagatgt ggcgtgttac ggtgaaaacc tggcctattt ccctaaaggg tttattgaga 36960
atatgttttt cgtctcagcc aatccctggg tgagtttcac cagttttgat ttaaacgtgg 37020
ccaatatgga caacttcttc gcccccgttt tcaccatggg caaatattat acgcaaggcg 37080
acaaggtgct gatgccgctg gcgattcagg ttcatcatgc cgtttgtgat ggcttccatg 37140
tcggcagaat gcttaatgaa ttacaacagt actgcgatga gtggcagggc ggggcgtaat 37200
ttttttaagg cagttattgg tgcccttaaa cgcctggttg ctacgcctga ataagtgata 37260
ataagcggat gaatggcaga aattcgatga taagctgtca aacatgagaa ttggtcgacg 37320
gcgcgccaaa gcttgcatgc ctgcagccgc gtaacctggc aaaatcggtt acggttgagt 37380
aataaatgga tgccctgcgt aagcggggca catttcatta cctctttctc cgcacccgac 37440
atagataata acttcgtata gtatacatta tacgaagtta tctagtagac 37490
<210> 43
<211> 24
<212> PRT
<213> 口蹄疫病毒
<400> 43
Ala Pro Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly
1 5 10 15
Asp Val Glu Ser Asn Pro Gly Pro
20
<210> 44
<211> 143055
<212> DNA
<213> 人工序列
<220>
<223> 载体
<400> 44
tatttattta gtgtctagaa aaaaatgtgt gaccaacgac cgtaggaaac tctagagggt 60
aagaaaaatc aatcgcttta tagagaccat cagaaagagg tttaatattt ttgtgagacc 120
atcgaaggag aaagagataa aactttttta cgactccatc agaaagaggt ttaatatttt 180
tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc agaaagaggt 240
ttaatatttt tgtgagacca tcgaagagag aaagagataa aactttttta cgactccatc 300
agaaagaggt ttaatatttt tgtgagacca tcgaaggaga aagagataaa acttttttac 360
gactccatca gaaagaggtt taatattttt gtgagaccat cgaaggagaa agagataaaa 420
cttttttacg actccatcag aaagaggttt aatatttttg tgagaccatc gaaggagaaa 480
gagataaaac ttttttacga ctccatcaga aagaggttta atatttttgt gagaccatcg 540
aagagagaaa gagataaaac ttttttacga ctccatcaga aagaggttta atatttttgt 600
gagaccatcg aaggagaaag agataaaact tttttacgac tccatcagaa agaggtttaa 660
tatttttgtg agaccatcga agagagaaag agaataaaaa tattttagtg acaccatcag 720
aaagaggttt aatatttttg tgagaccatc gaagagagaa agagataaaa cttttttacg 780
actccatcag aaagaggttt aatatttttg tgagaccatc gaaggagaaa gagataaaac 840
ttttttacga ctccatcaga aagaggttta atatttttgt gagaccatcg aagagagaaa 900
gagataaaac ttttttacga ctccatcaga aagaggttta atatttttgt gagaccatcg 960
aagagagaaa gagataaaac ttttttacga ctccatcaga aagaccatcg aagagagaaa 1020
gagaaagaga tagttagtct agatattttt cttagtacaa aagtcaatgt tttaaaatat 1080
atggacaaga atttgtctgt ataaaaactt gtgtgaaatt ttgtaccaaa gaaaaaatgt 1140
gagcagtatc ccctacatgg attttactag atcatttata taccaaaaaa tattatacga 1200
tctacgtttt attatatgat tttaacgtgt aaattataaa cattatttta tgatatacaa 1260
ttgtctggta acctagatgg gcatagggga tgagtatatg ttgttggacg ttattgttta 1320
agaaatagtt gatgcatcag aaagaggttt aatatttttg tgagaccatc gaagagagaa 1380
agagataaaa cttttttacg actccatcag aaagaggttt aatatttttg tgagaccatc 1440
gaagagagaa agagataaaa cttttttatg actccattga agagagaatg agaataaaaa 1500
tattttagtg acaccatcag aaagaggttt aatatttttt atgagaccat caaagagaga 1560
aagagaataa aaatatttta tgactccatt gaagagagaa agagaaaatg agaataaaaa 1620
tattttagtg acaccatcag aaagaggttt aatatttttt atgagaccat caaagagaga 1680
aagagaataa aaatattttt gtaaaacttt ttttatgaga ccatcaaaga gagaaagaga 1740
ataaaaatat ttttgtaaaa ctttttttat gagaccatca aagagagaaa gagaataaaa 1800
atatttttgt aaaacttttt ttatgagacc atcaaagaga gaaagagaat aaaaatattt 1860
ttgtaaaact ttttttatga gaccatcaaa gagagaaaga gaataaaaat atttttgtaa 1920
aacttttttt atgagaccat caaagagaga aagagaataa aaatattttt gtaaaacttt 1980
ttttatgaga ccatcaaaga gagaaagaga ataaaaatat ttttgtaaaa ctttttttat 2040
gagaccatca aagagagaaa gagaataaaa atattttatg actccattga agagagaaag 2100
agaataaaaa tattttagtg acaccatcag aaagaggttt aatatttttg tgagaccatc 2160
gaagagagaa agagaataaa aatattttat gactccattg aagagagaaa gagaataaaa 2220
atattttagt gacaccatca gaaagaggtt taatattttt tatgagacca tcaaagagag 2280
aaagagaata aaaatatttt tgtaaaactt tttttatgag accatcaaag agagaaagag 2340
aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa agagaataaa 2400
aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa taaaaatatt 2460
tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa tatttttgta 2520
aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt atgactccat 2580
tgaagagaga atgagaataa aaatatttta gtgacaccat cagaaagagg tttaatattt 2640
ttgtgagacc atcgaagaga gaaagagaat aaaaatattt tatgactcca ttgaagagag 2700
aaagagaata aaaatatttt agtgacacca tcagaaagag gtttaatatt ttttatgaga 2760
ccatcaaaga gagaaagaga ataaaaatat ttttgtaaaa ctttttttat gagaccatca 2820
aagagagaaa gagaataaaa atatttttgt aaaacttttt ttatgagacc atcaaagaga 2880
gaaagagaat aaaaatattt ttgtaaaact ttttttatga gaccatcaaa gagagaaaga 2940
gaataaaaat atttttgtaa aacttttttt atgagaccat caaagagaga aagagaataa 3000
aaatattttt gtaaaacttt ttttatgaga ccatcaaaga gagaaagaga ataaaaatat 3060
ttttgtaaaa ctttttttat gagaccatca aagagagaaa gagaataaaa atatttttgt 3120
aaaacttttt ttatgagacc atcaaagaga gaaagagaat aaaaatattt tatgactcca 3180
ttgaagagag aatgagaata aaaatatttt agtgacacca tcagaaagag gtttaatatt 3240
tttgtgagac catcgaagag agaaagagaa taaaaatatt ttatgactcc attgaagaga 3300
gaatgagaat aaaaatattt tagtgacacc atcagaaaga ggtttaatat tttttatgag 3360
accatcaaag agagaaagag aataaaaata tttttgtaaa acttttttta tgagaccatc 3420
aaagagagaa agagaataaa aatatttttg taaaaattat aaacattatt ttatgatata 3480
caattgtctg gtaacctaga tgggcatagg ggatgttgat aagctcgacg agtatatgtt 3540
gttggacgtt attgtttaag aaatagttga tgcatcagaa agagaataaa aaatatttta 3600
gtgagaccat cgaagagaga aagagataaa acttttttac gactccatca gaaagaggtt 3660
taatattttt gtgagaccat cgaagagaga aagagataaa acttttttac gactccatca 3720
gaaagaggtt taatattttt gtgagaccat cgaaggagaa agagataaaa cttttttacg 3780
actccatcag aaagaggttt aatatttttg tgagaccatc aaagagagaa agagaataaa 3840
aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa taaaaatatt 3900
tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa tatttttgta 3960
aaactttttt tatgagacca tcaaagagag aaagagaata aaaatatttt tgtaaaactt 4020
tttttatgag accatcaaag agagaaagag aataaaaata ttttatgact ccattgaaga 4080
gagaatgaga ataaaaatat tttagtgaca ccatcagaaa gaggtttaat atttttgtga 4140
gaccatcgaa gagagaaaga gaataaaaat attttatgac tccattgaag agagaatgag 4200
aataaaaata ttttagtgac accatcagaa agaggtttaa tattttttat gagaccatca 4260
aagagagaaa gagaataaaa atatttttgt aaaacttttt ttatgagacc atcaaagaga 4320
gaaagagaat aaaaatattt ttgtaaaact ttttttatga gaccatcaaa gagagaaaga 4380
gaataaaaat atttttgtaa aacttttttt atgagaccat caaagagaga aagagaataa 4440
aaatattttt gtaaaacttt ttttatgaga ccatcaaaga gagaaagaga ataaaaatat 4500
tttatgactc cattgaagag agaatgagaa taaaaatatt ttagtgacac catcagaaag 4560
aggtttaata tttttgtgag accatcgaag agagaaagag aataaaaata ttttatgact 4620
ccattgaaga gagaaagaga ataaaaatat tttagtgaca ccatcagaaa gaggtttaat 4680
attttttatg agaccatcaa agagagaaag agaataaaaa tatttttgta aaactttttt 4740
tatgagacca tcaaagagag aaagagaata aaaatatttt atgactccat tgaagagaga 4800
atgagaataa aaatatttta gtgacaccat cagaaagagg tttaatattt ttgtgagacc 4860
atcgaagaga gaaagagaat aaaaatattt tatgactcca ttgaagagag aatgagaata 4920
aaaatatttt agtgacacca tcagaaagag gtttaatatt tttgtgagac catcgaagag 4980
agaaagagaa taaaaatatt ttatgactcc attgaagaga gaatgagaat aaaaatattt 5040
tagtgacacc atcagaaaga ggtttaatat tttttatgag accatcaaag agagaaagag 5100
aataaaaata tttttgtaaa acttttttta tgagaccatc aaagagagaa agagaataaa 5160
aatatttttg taaaactttt tttatgagac catcaaagag agaaagagaa taaaaatatt 5220
tttgtaaaac tttttttatg agaccatcaa agagagaaag agaataaaaa tatttttgtg 5280
agaccatcaa agagagaaag agaataaaaa tatttttgtg agaccatcaa agagagaaag 5340
agaataaaaa tatttttgtg agaccatcaa agagagaaag agaataaaaa tattttatga 5400
ctccattgaa gagagaaaga gaataaaaat attttagtga caccatcaga aagaggttta 5460
atatttttgt gagaccatcg aagagagaaa gagaataaaa atattttatg actccattga 5520
agagagaaag agaataaaaa tattttagtg acaccatcag aaagaggttt aatatttttt 5580
atgagaccat caaagagaga aagagaataa aaatattttt tatgagacca tcaaagagag 5640
aaagagaata aaaatatttt atgagaccat caaagagaga aagagaataa aaatattttt 5700
tatgagacca tcaaagagag aaagagaata aaaatatttt atgagaccat caaagagaga 5760
aagagaataa aaatattttt tatgagacca tcaaagagag aaagagaata aaaatatttt 5820
tgtatgagac catcagaaag aggtttaata tttttgtgat accctgaaag gaaataggaa 5880
tagtgtcata atcgtatcac actattgaga cagaaaaaga agaagtcgcg agaggtaact 5940
ttttgttttg caaaccggaa tatagtgtcc ggtacacttt tttaattcgt ggtgtgcctg 6000
aatcgttcga ttaaccctac tcatccaatt tcagatgaat agagttatcg attcagacac 6060
acgctttgag ttttgttgaa tcgatgagtg aagtatcatc ggttgcacct tcagatgccg 6120
atccgtcgac atacttgacc tcaagttcag atgattcctt gcacatgtct ccgatacgaa 6180
cgctaaactc tagattcttg acacattttg tatcgacgat cgttgaaccg atgatatctt 6240
cgtaactcac tttcttatga gagatgttag acccgagtac tggatgggtc ttgatgtcgc 6300
tgtctttctc ttcttcgcta catctgatgt cgatagacac ctcacagtct ttccatcagc 6360
ggattctgag atggatttaa tctgaggaca tttggtgaat ccaaagttca ttctcagacc 6420
tccaccgatg atggagtaat aagtggtagg aggatctaca tcctcgactg attccacctc 6480
gggatctgga tctgactcgg actctgtaat ttccgttacg gattggcaaa tcttatcatc 6540
ggtcggtgtt tggtcttgct ttgtgacttt gataataaca tcgattccca tatgatgttt 6600
gttttcttct tccgtacacg atgaggatga ttgctgaaga ctggcaggca catgcatgcc 6660
agtacgatat attgtttcat gattgctatt gattgagtac tgttctttat gattctactt 6720
ccttaccgtg caataaatta gaatatattt tctactttta cgagaaatta attattgtat 6780
ttatgggtga aaaacttact ataaaaagcg ggtgggtttg gaattagtga tcagtttatg 6840
tatatcgcaa ctaccgggca tatggctaca ttacccacat gataagagat tgtatcagtt 6900
tcgtagtctt gagtattggt attactatat agtatataga tgtcgacgct agagttactg 6960
tctccgaatg cggcatgata gtatcattct ttgctttcgt taactgtttg gaggaagaat 7020
ctttgttatt gcatttaatc tcgaaattca gagtgcacac ctttctcctg taaagaaacc 7080
tgaagtcgct accttattaa gaagacggga tcgcagtctt tatgattcat agtaatagtt 7140
agttccgacg ttgagatgga ttcgctgaga ccggtagtgg tcgtccgagt acacgatgtg 7200
tcgttaactg gatacaggtt aatttccaca tcgatatagt taaaggtatt tctgggtacg 7260
ggttcgcatt tatctgcgga agagacggtg tgagaatatg ttccgagacc acacggagaa 7320
cagatgacgt ctccggatac tccgtatcct attccacatt ttgtttggga aacacatgcc 7380
ttgcatccat gatcgggaga gcattcacag attctattgt gagtcgtgtt acacgatcgc 7440
gtcgacattg ttgacagaaa cgtgaccttc attcttaccg tcgtccataa atacgttagg 7500
tatgtaccac atactgtcgc gaacgatgcg tccatctcat aatgatttac tttttcataa 7560
ttaaagatgt gaaagaaaac cgaacaatat atttttttag taatgtttat gcgagacata 7620
taaaataaac tccgtgttta tgatgccggt aaatgttttt atcatcttgg acggaatcga 7680
ttttgtaata tgccatggaa acaggacatt atcactccat gataaattat ttaatggagt 7740
cgatcctctc attgttcttt gcgtatctca atctgtggcg tttgcttcgt ttaaataata 7800
tatcaaacat ggagacgcct gatatgtagg cattcttcat tctattaatg tctgctctat 7860
agcgctttag ttccttatga cgaccggcga tatcatactt actttagaag gaaaatcatc 7920
atctaggatt aaggcgtatc tgatacaggc gaataatggt tcaggatata gatagcgtat 7980
atctctatta aatgcgtcaa tcatagtctc tagagtggga tggtaactca gtaataaatc 8040
aactagcttc tctttggtaa ctgcttttct ggatggccgt attgattatc gagcgtgaca 8100
ctcgctccat attccaataa ccgctttgca aattgtatat tattgacatc gaccgcgtaa 8160
tatagtagag ttatcgatca tatctatatc atccatgtac ttgcttagta tatcaaatac 8220
atcttcataa cagtgatacc cgcaattatt aaatctcgat aatatcagac cgtacataca 8280
tagacggcca ttgttagata tgtgatttac agccgcgtgt ccatattttc cacgataaac 8340
cttacgacgt ttacatcgac gagattatta ttaacaaagt tgttgtccgt cgtcttatcc 8400
aacatgcatt gaatgatagg tatacttacc atatcgccgt aatgtaagta gtttatcagt 8460
atggcttgta cgatggattc atcctgttgt ctaaatctct ttagaatgtt atcgatgatg 8520
tagtggttat attctctgga atcgtacgaa gtaatactac gcattacgtc gacaagagta 8580
tgacgtctct caataagaag attaacgatt tccatgtcta cattatatgg ggttactcta 8640
aatcgcttgt ttagataata cgcctctaat atagggctga cgtcgtatac tctacacgtg 8700
tccacatcct ttattaataa tctctatatc tatggttgag caagaccagt agtattggat 8760
ggaaacattg ttatcgatca aacatttaat tacatccttg gatagagatt ctctatgaga 8820
cgatatatag taatgaagag agttcttaca catatcactg ttgtacatac aggtacgaaa 8880
tacgtaaccg gtgctgtaac attctgattt aagaagccat agcaatactt ctggtctcgg 8940
attaggcgtc gttacgtata tatccaccaa tccgagacca ttgattgcat aattcgtatt 9000
cttggacgga cgtatccgtt tatccacaat taggtatttt agcagacgta agtcgaaatc 9060
atttatattc gacttgagtt cgttagagga attcgaatag ctggatatca gtagatgcac 9120
aatctgagat tttacgtatc tatgcttact gtatgctcct agcggagtta atccttcgtt 9180
gtttctacaa agtctctcga ctccgcgaga gagtaacagt cgaacaatct taatgtctgt 9240
atcgcattta ttggagacgt aacaatgtag cgcattgttt cctcgtctat ctatatgttt 9300
tgataagttg tgacacgttt caatttctag ttttattttt ttgtacgtca catcttcatc 9360
cagtagacga catagaatac atgtgcaatc catagctatt ctggtgctaa ttattcctca 9420
taagatgata aaaagtgtag tgagagagca tgaaggagat ttagtattta gcagtgcgga 9480
tatgatccaa gagggtgaga tagtcgttct cgttcagaat ctttcgcagc ataagtagta 9540
tgtcgatata cttatcgttg aagactcttc cagagacgat agctgattga gtacaaagtc 9600
caatgattgc acgaagttct tcggcggttt tcatggagtc atttaatgat ctccacggaa 9660
gtgaatcctt caactcacca ccaaagagct ccgttgcatc agttctgaaa gagatgagaa 9720
gcctgtagag agaccctgcg ctttctctat gggtccatct atgagaaacc cacaggatgt 9780
attcagtcag acaatgtctg acgtcggcca cggtattcag ggagtcctta gtagcgtggc 9840
aatgacaggg tctgaactgg gcacaaggaa aggccattgt aaaggtagac ctgtagccgt 9900
ttatgctaat agagggcttt aatttccatt ttttaatggg ttgtggatga ggaatgagag 9960
tgatatcata ttgagatacg tagttatgta gaggtgtatt tcctatatta tttactttcg 10020
gtttcatatt ttaccaactc tttaataaat ttcttttcac gatgcatctt attaaatgac 10080
gttttctcat aagtggacat atagatgcag aagtattacc tctatcatct acataattag 10140
ggtctgctcc taacttatac agtacgtagt agtagtttat cggttttaaa tcaagtctag 10200
aatatatagt ggattaatat atttttatat tagctaaagc atatcattct caacttcatc 10260
atgagttaaa tatttgtgtc tactagtttg tttatatcac agcattctac aaacagtcta 10320
aacaatagag aagacggaca gactttaacg tataaatgac acatgttatc gatattcgtt 10380
gataaatgat tctaacgaca tctctcgcta gagataaaat ctagtatcgt atcatactcg 10440
catagcatag tttttcataa ttaatacaat atttaaaaga cttattcgga aagtatttta 10500
atacatgtat catcgatgga gatccatatg aggagtcact tgtagttctt cagtagtgct 10560
atcatcgata gtataattat atgttgttgt aattggagta actgttggta gttcttccgt 10620
ggaatcaata attatactaa cagcaatagt ataattatat aaatatgttc cgttgatatc 10680
acatatttta atgaactcat ttctaaagcc gtacatccac atctattagg atctgatatt 10740
ttacacaact gtttaataga gtctacattt atatgttctc tatcggtgag atacaaatac 10800
ctagatagtc gcgttatagc acaaatacga tataaataat aataataatt attcagtaat 10860
gtatataaaa atgcattgtg tatttactcc aatactactg tagttgtaag ggttttttca 10920
aaataatagt tgtgtccacg acatttatat gtattaccta tatattcttc agtaacattt 10980
tcaaagtaca aggtcgcctc ggtgataccg cctctactag ttaaaacaga gtatacatca 11040
aaatcgaatc ctataagcca tccggatgga ttttcccatt caatcagtac atcgtcaatc 11100
aataatgacg ttgacacagc agtgcatgtt atattggcag gttctcctat cgttacgttg 11160
atttttggat ctagtattag tttaaacctg tggtcttgcg acggtataac cgtaagtatt 11220
ttacatcttg attctaacgt cgtcgtaatg aacgtaacag ttgtatcttc cactatcttc 11280
taactctgga ttatgaataa ttaatttctt tcccgtttgt gaatacttaa tatcgtcgat 11340
attaatttcc ttattatctt tataccaagt tatattatta taatgttttg cgtaaagaat 11400
tccacagtat aagtctatgc catacttatc atgagtacct agttcatatg tttttggaat 11460
gcatgaagga ggttttttaa tatgagatct aactataccc tgaacacagt caccattctt 11520
tgtagttacg gtacacaaat acctacggtt actgaattta gatgtatagt tggctatcca 11580
taaatcacca tgtttaacac gtttattaga aacctgtcgc cgtctatttt tttctagcct 11640
ctcccattta accacatagt ctttatatct gtgcgataaa agactgtctt caataggagg 11700
acactttgcg ctgaatggct ctcctagagc ggctatatca ttcattgtgc ctccgaacat 11760
acatgctgga ttcaaccatt tagagtcttt agctggtaga gtatctctca ttttattgaa 11820
gaattctgtg atttcatttt cgatgtctat ggcgtaactg tggaatagca ataacaataa 11880
tgatacgaaa tatatatgta ccatcatttt catcgtcatc ttcattatac ggcactaaaa 11940
tatttatata atatcagttt ttttacacac atcgcatgag aaaaatacaa ctatactttg 12000
gtaggtggat acgatatatt ataaagatcg ttaattgtca gcatgtataa tatttcgtat 12060
ataatttctg aaggtagtaa tgttagtaga caatttttat ctgtgaaaac aggaaatagt 12120
ttatcatata cctttgacac gtacatatct ttataatata cattaaggta tctctcattc 12180
ataatattag aatatatttt aaaggactta tcgttattat atttttttaa ctcgttgagg 12240
tatcttctta actttttcga attatggcat cttaaaactg catatagtgt agtgtctaga 12300
acagtggata gtttgagcaa tattgtttct ttatgacatt tagttattat accatcgtat 12360
ttatcaaacg acatgtattt tgaaaatgcg tatcgatacg ttttagaatt gcgattccta 12420
acgtgtctat tgtaaaatgt gtcatctaaa agtatacagt aggatatgaa tttctcaaat 12480
gattttatat cgaagatagg tagagatgga agttgatcca ccaacgatct tatcacattc 12540
ttatctacaa tatatctaag tatatacagt aaacaattaa tggtatatgg ggaattttct 12600
ttgttatcta taatgagttg tgtagcgtgt ttgttattgt cggttaacgc atttatatct 12660
ccgttgatac gtataagata atctattacg tgtgtattat tatattcaca tgctacgtgt 12720
aataatgtct ttccttcata gcgggtataa atatctatat ttttaaacct attcatcaaa 12780
taagttatcg aatctgccgg acgtgtagaa tatgttttga taaactcgaa tacgattata 12840
cgacgctcat ctatcggcat ttctccaaca tttgtttcat agtgatgtat taacataaca 12900
agaatatcgt gttgtatgta gtcggaagtt atataacata gtataggcgt taatccatga 12960
ttattacata ttttgaaatt cggattaaaa gtcaacagca ttttagtcat atgaatatta 13020
ttacacattt caatactaag atacaaatgg aatggtgtat taccacaatt atctaacgcg 13080
tttagattag ctccatgttg tataaacaaa gaaataattc gcttggcctt ttttatcgtt 13140
atcggttttc tacactcacc tggtttataa acgtgtgcga gacacaaata ataataatgt 13200
aacgctgtat atccgtcttg tttaaagtta ggatcgattc ccttatctaa taaagtggat 13260
actatgttct catcgatatc ctcttccttc aataacatgt aacgagattt tatatactct 13320
agtagtaggt tggaatagtc tctatgcgat aagtggtttt tatctttgtc tatcatatct 13380
atcactacat catgtgaaat attacaacat ctagtaagca atatataaac aggcatacgt 13440
ccgctactgg ttttcatcgt tacatccact ccatgattta ataatatctt cagtacatcg 13500
tttgtaaagt aattattata caaatagcag tgtagtgcag tatacccagt tacaggttgt 13560
cgtctgttta gatcatagtt tttaactaca aaatcaagtt ctgtagaagt atggtctata 13620
ttgcaatgac taaaatatgt atatatttca ttctcttgta ttttatgagt tgattcgcgg 13680
ttgatattta aaacataaat cagacgacga ctcattttta tgatgctttg tggtaaaagt 13740
cctcatataa ttgtttaata ttcattatta tagacgattc ccattaacta atctaacatc 13800
tttgatatac ccgtaaatat gtaaatatga tcctaaaata acacggattg taagatgtct 13860
agaaagttta tgcaggtgta tgaatatgac agagagcaat atctcgatga gttcattgaa 13920
gacagatata acgatagttt tatcactagt ccagaatact atagtgcgga aaaatacatg 13980
tgtagatata ctacactaaa tcacaattgt ataaacgtac gacgatgcgc gttagactcc 14040
aagttattac atgatatcat aaccaattgt aaaatatata acaatataga attagttagg 14100
gcgacaaaat ttgtttatta tctggatctg ataaaatgta attgggtatc taaggtaggt 14160
gattcagttc tatatcccgt tatatttata acacatacaa gcactagaaa tttagataaa 14220
gtctctgtaa aaacatacaa gggcgttaaa gtaaaaaaac ttaatagatg cgcggatcat 14280
gctattgtaa ttaatccatt cgtcaagttt aaactaacgt tgccgaacaa aacaagtcat 14340
gcaaaggtat tggttacatt ttgtaagtta agaacggata taacgcagat agaggcaccg 14400
ctttcgggca atgttttagt ttatacattt cctgacatta ataaaagaat tcctggatat 14460
atacatgtca acatagaagg atgtatcgat ggaatgattt atataaattc ttcaaagttc 14520
gcgtgtgttt taaaactaca tagatcaatg tatcgcattc caccctttcc tatagatatc 14580
tgctcttgtt gttcacaata tattaacgat gacatagaaa ttcccattca tgatttaata 14640
aaggatgtgg caatttttaa aaataaggag acggtatatt atctaaaatt aaataataaa 14700
actatagcta gatttacgta ctttaataat atagataccg caattacaca agaacatgag 14760
tatgtcaaaa tagcactagg tatagtctgc aagttaatga ttaataatat gcatagtatc 14820
gtgggagtta atcatagcaa tacgttcgtc aattgtttgt tggaagataa tgtataaaaa 14880
ttcttataaa ctcaattgac atggaaatgt aacaacatac attcacgtta tactaacagt 14940
aactgttttg ctgatgctag gaatagtaaa cgccatacac gtaaacgttg tagcatcttc 15000
ttccttgaca ggattaatgt ttaaccggga tgtaataaca cgtctcttat cggtcatata 15060
gattttattt gctacactta ttctaccgtc tccgtcccca tcatcttctt cgtaatacat 15120
accattactt atccaaaaga cgtctgcatc cgttgtggga ggtctcaacg atactctaca 15180
cgcaatagtc aaattactac ctattgaagt tacaacacct tctggtaatt gcatagtaga 15240
aggtattatt ttatcccgta cctctaattt tacaattctg gttacgttat atgttttgcc 15300
accgtatata tattctaaaa cacatgtata ataaccagca tcattttttc taacatcttc 15360
tatggtaata attccaggtg tccgttgttt aagtctctta tttctaaggc gtcgatgccc 15420
gctccatata atatctgcgt ttacgttact agcaataaat gcattaatat tgggacatac 15480
catttcgcca gtagatctct catttactat ttgtggatac gagataagat ctatatttga 15540
ttctgagaca gacacgattg tcaaatttaa cgacatcatg tcacagtagg tttcgttcgt 15600
ggtaatgcat atataaatac cagagtctga ttgtgtcggg ttcagaatta gcatattgct 15660
accattatct atcggtataa ttctatcatt atccgctcct cgtttttccc ataaaatatc 15720
taatatatta tatccggatg atagcgtatt tatttgagga catggtaaga ttactggctc 15780
gttttctaac tccatgaatg atgcaaaata ttgccctttg tcgatacatt caggcgcgtt 15840
aaaagtctga acgaatgaag aataaaaaaa tatagaaaga aatataacag gtagtatact 15900
cattttattt tatagtgggt aaaaaaagtt tgtttctggg aaagggagaa gagaagaaag 15960
aagaaaatgt caagatgtac aactcatcaa ttcatacgcc ggaatatgat gttataatcc 16020
acgtaattta gcatctcaag catcacaaac aatgcgttca gactgttact agtgggatgg 16080
tcttcacctc cccagtaagt agcagcatat gcacaaagtc cgatgatggt tttttgctca 16140
tccggtatat aacaacggat gatttctaca caatctttga catcatccca cggcatattt 16200
tttaccagct cgcgaatgtc gatgaacact aattccgcat catctctaaa agagaggagt 16260
gtggaataca attgtccagc gcattgcctg ttgcggtatg cataggacga ccaataaata 16320
tattcagtca aacattgttt gacgtcatca atactggtca gtctgtcaca tccacagtgc 16380
tgtggtgaaa agacgtgggt actaaagttg gccgtcatct taccaattgc aattggaaga 16440
ataacgacct gcactaatac cacatgtttt ttctattttt ttaaaaaaaa tggttaacaa 16500
ttagttgtcg gagagcaata tctaccaacg aaaaaaattt ttccatcaac atgcctaatc 16560
acatagatga acggatgatc tacacagaac tcatttgtaa ttgttgatgc acagtctgac 16620
accagtgcac aagttgctgc agctgcttct gtatactctt cattgacatc tatatacgtt 16680
ttgtggatca tagcgtcgac actcacatct aaattacaca tattgctata atctccagtt 16740
gaaccgaaca cctctgtcag tcctgacttt actagagtat ccaccagatt atacgagcct 16800
gttaccttaa acttgggaat gtgaacatcg ataaacgtag cttccagaga gttacaccat 16860
ttcttaaaat ttgtatctgt tagattttgt tctatggatt ctaatccatc aatcttgtct 16920
ggaagaatga ccatcatact agtatctcca acatatggca gttctatgat tgaaaagtta 16980
ccgaatgatt cttttacaga tgcgtgatta aatagctcgc cgtacataga catcatactt 17040
acgtctacca tttccgttgg tgatacgtaa aagggataat cactggtaaa ttccttttcg 17100
aatggcgtca accattttgc tttaaagtat acggcactaa ttgctaggag acaattgttc 17160
atccaatagt ggattgattt tcccctcagt aaagatatct acacacttgt tgattgcatc 17220
tatagtgcga caatcagtga agtcaacagt ttgaaactta tcgccaattt ttctcaaaaa 17280
ggaatcttta aacacggcag aatatcgccc atatacttta ttcatggatt tgaatgagat 17340
attctgagcg ctaaccttat ccgtgttctc ctccttttct acatattttg atagctgttc 17400
agcagtggat ccattagctc cataatacag tattgtcaat actgacgaga ttgacgctgg 17460
agaaatgaat acattctctc ctttcataga agatatccat agtaatcgat attggtcgtg 17520
tagcgcgata gagatagtct aatattaata ttagatatcc gtaacactac cacactctat 17580
aaaaaaagaa tatttcaatc ttgtataaac agtctacgta gtctgtcata attaggagtt 17640
tgagaataat ctaacgtgta tactaattct atatatctaa ctaattccag aggttcattt 17700
ccttcaggaa aacagtcctc aaagaaagta gctataaatt ttttatattc ttttttttgt 17760
tttattactt ttatactact ttcgtttttc catggaagtt tgccaccgaa ccattctatc 17820
atgcaatatc ccaacatttc taaatctcct cgttttgaaa ctgttgctcc aagatgattg 17880
tctacacaca tataattgat atttcctgaa gttatcatgt cctcgttgta atctatatgt 17940
gagtttccac tcttgtatag tttgttagtt ctagaatagt caattagtga aagacgttta 18000
tttctaatca gtatattcct cggttctatt tttccatggg taaatcctcg agagtgtata 18060
aactctaacg tgtttatcat agtgacgcat gcttcgaaga ctgattcagt atcctttggg 18120
gcgaatactc ttcccaaatt ctttataacg aagaacatat aatcatcggt ttctccaatt 18180
ccatacagat ctggaatagc caaatacttt ataccacgtt cccgtgtcca gttgtcgata 18240
gtcaaaggat ccaatacaga tatatagaat cgtatttcag acaacaatgg cttgtgtgat 18300
ttgtgatcta tcttcattac gtaattgtag aacgaactag tgaaattttt tctgacctta 18360
tagagtattg aattaccaga atataaagta tttccgataa tccatttctt gccatcgtta 18420
tcaaaacaat acttgaagga ttccatgcct gctatgtaat aacgagttgt tttttatgtt 18480
ttgtattgat tataaaaatt agtagatatg atctatattc ctacatcgtg actgatacat 18540
tctataactt ctttatcaat ggaatcacta ttactacttg tattaataac gagtgcttct 18600
ctaatatatt cattgggatg attcttgtta atgtttttat tattttcaat ttctacattt 18660
tttagtattt cttctttctc tctatctatt tcattcatga tatcttctac atttgtaaca 18720
tctgtatctg tatccatgtt agtagtaagc aataaaacta tagggtaata ctgctataca 18780
taaaaactat ttatattttc attttcaatc aataaggaga agttgataat gcctttatag 18840
cggggagacc atcatacttt tccacatatc caatgtcctt actaaataca tagaagacgt 18900
tatttagttt acacaatgat gatatggata tcttataaat agtatatgaa atatcaaacc 18960
acttattcgt tctaggattg taacaagata tctcgttgtt tttctctaaa ttaccatatt 19020
gttcggtaac ggatagacct ccggcaaaat ataacattcc aaatgtcgag tcgatgccgt 19080
gatataccct agccataggc atttctataa tcgaccattg tttgtcttta taaatgtcaa 19140
gtttttccat attgttaacc acgatcgtgc tattagagtt atttatgaat aatccgccag 19200
ttacgaaaat agtattatta acggaaacag cggacacatt gcttttttta taatttatcg 19260
gtgtttcgta tatccctgaa tccattgcct tcacttgcag ttgggagatg aacactgcaa 19320
tcagttcttt cgggatagaa atctttggca attatacaca accctatttt caatccccat 19380
gtttcctctt cagtcttctc acatcgtcta atagacatgg agtagatgat agaggggaac 19440
agaaggacta taatcaggga cctcatcttg aaaatggtta gagcctataa gggcgttaac 19500
cagtgtataa tatgcagttt tatttcgttt ttgtatcatt aataaaaatt agttatgaat 19560
atttagtcaa gttaagcatg ctaagaaaag tggtaacatc atttgatgtg ctaccgagaa 19620
atttagttaa attttctctt gataactctg gccattttgt ccttgaaatt gggaacatct 19680
tctttggatc taattgcgca tgtatataca ctctttttag gtgtcagaca tactttcgaa 19740
ctccatggag taattttttc gagaaaccct tctgtggctc cctgtgctgt cacgcacact 19800
ttttctgttg tgacaaagtc tatgctgcaa cctgtagacg tgcaatcgta gtcatcgata 19860
tcatatggta ctggttcttt agaatctccg aatgtgaagt tagccgtata caacaagtag 19920
atatcacaca tgtcaccgcg tttgtaaata ggaatctttt tgctacctct agtagcatac 19980
ggatggtcgt cgtattcagt taatgttaca gtcggtggtc ccgtacaata ctcttccact 20040
ttataatcgc cttgttcaaa tttaacccag aaagatacga aatcattctt tggaaatgcg 20100
gatatgtcgt atgttccttc tggtacattt gtatacattg tttgccacgt cttgatgcca 20160
taatttttaa gggatatatt gtatagacca tccccagtcc attcaatttt ggaatcaaaa 20220
ttgacggatt caaacttata actagttatt ttagcgtgta tactattaat gaacaaaact 20280
gcgagaatta taatatatct catggtgttg tttgttattt gactactgtc actgaagtga 20340
taatatattt taaattttta aaaatcatat tttgaataat atgtattact atgtccatga 20400
cgatcaaata tataagtaga tccaatttta agagtatgtt ttctcaatag agtatcatcg 20460
ttgatcatac ttatttcata ttttattcct ttatagcatt ttccctctgc agtaatagaa 20520
tattgtcgct catcaccatc atatttgtga atataagggt acttatcata atggcatgat 20580
aatttggtag atattctaca cgtgtgacct ctgcgttgaa tagtagacat atcaataatt 20640
ttatagtcgt ttataacatc tatatctatg gaatcaaatc cgacgtcgca tgactctgta 20700
ataatagaaa ttgtgtactc tttaaaattt aacaccaatt cattattatc atcagtatat 20760
gaattttcta tattatctac tccatctata tagagtttta cactcagttt attaaacgga 20820
gtgtactcat tattcgaata ggatgctaat gcacctatta caaataaaaa cgttattagt 20880
tttttataca tttaaaatct taaaatttta actagtatat tgaaataatt atttatacaa 20940
actaactaga tgcatcaaca gataataaca aacacctcca gcgatcgtgc caatagtagt 21000
tagagatgcg tatccgtaca acttgttaat catatttcta cggatgtata taccatcgtc 21060
gttaaaagcg cttctatatc tctcattagc tagaattata gatacgctat taattatatc 21120
atacattagt tgattgttga tactattttt attgtaatcg aaaaacattt ccatgaatag 21180
tattccggtg ccaacgctta cagaaacatc gcgttcattc atcattatac cattaagtgt 21240
atccatcacc cattgtttaa cacgtgattc atttggcata gtacgtacta tatcatcgaa 21300
cggtataacg gcgcatcttg taaatagcct gtatatatta tgtaatatgg cgttacttct 21360
tccatacaca ataaatctct tgttataata gtgcctgagt aaaaatgctc taacggcatc 21420
gtagatatca acatccactg aagaagacat ctcaattgat tctagctata agtctttaat 21480
cttttgatac ttgtttgtta ttaaattatt aattattaat tattcattat tttaacggat 21540
ttatattcac ggtagcaatt tatggaactt atattggtca ttatttttgt cacaggaaca 21600
aactaatact ataacggaga ttaaaaatat gacgcccata attgttaacg ccactatgat 21660
tatatgataa gttgcttcta acgattctat ttcttgttca tattgtacaa cgtctttcga 21720
gagtttgctc aaatctgtct catcgtcggg accatcatcc actggatcaa atttttcgtt 21780
agatcgtaca catgttggga gtatgggatt ccatttaccg tcgatacatg tggatgatgg 21840
agatcccgtt agtataaaac cacttttaca actaagatgt ataacgccac cgatagaaaa 21900
tgtagatccg gaaattaatc cattagatag agacggtata tcacattttt gttgacatga 21960
tggaataaca ttccaagaat tagctgtaca acttatgtac gaagcaccaa taacctcata 22020
tccaacatca cagttgatag ttatatattc cccaaatgag tatttttctt taactggttg 22080
acacgatccg tgttctaatt gaagaggttg acattccgca ttaggacacg taacagtatc 22140
attccaagaa gtatttccat ttttttcttc gcaacgaaaa tattttgttt cgccgttgca 22200
acttagtgtc atggtggaat tcacttcgta tagcggttta ttatatagtt cagagatgta 22260
atcagaaact gtgcacattt ttttgcatgg attttcgtat ttccatttat ctgtttcgca 22320
gacagcattt ggatccgaag aatgatatcc ctgatcacat gtaaacgtaa ctttctggtt 22380
attattaaac gatgtttcgg tagacgttaa tttagcgtta ttcatagtgg gtacagtaca 22440
tgttgaataa acaacagcag gtagtacgca taacaacgta acaacggaaa tcgttttcat 22500
ttttatttat gagcgttaaa aatagtatac actgtcgagc actaaaagga aacaatgatg 22560
tagtgtgatt ttatatttta atagtgttta taagattttt agatatgtgg acagttcgtt 22620
atcgttatat tttatttcgt taggaaaaca cgaccattta tctccaggat ccagcttctt 22680
ggataataga ctaattaatc tctgacgata tctaatagat gctatgatat tacgtacacg 22740
acttccgtat acgtcgagac tagtgcactt cacgaaagaa ggatgtttac cgtatctcat 22800
taaagtatta atgtctttga tacaaaaaac taattggaat acagttttat tttttatata 22860
acatctcttc atgatatcta tttcatcgaa acatcttaaa atataccatt tatattgctg 22920
tagtgattgt acatctataa gagtatcata atcggtcata cacgcagtat attttataca 22980
cattttcaat aaatctgcat tatgctgttt atgtttagta attgctatca tagactgtat 23040
cataattttc aaagatggtc gtttagacaa tagtacttcc attattattt tgttgttgtt 23100
tgcgactgct tccgaaatac atgtacatcc actagtagta atcgtctcaa aatcaccatt 23160
tctgtttaat agatagacca acgtattata cgcattataa ctgacagcgt cgtaaatagt 23220
acgatagtta atatcaataa ctcctctgga taatagataa tctaaagatt caacagcatc 23280
aaaaattatt aaatgacgaa ctatatgttc attatctatt tctaactctg tgtctgattc 23340
caaatatagt tttataagcg agataccgtg tataattcca caataaaatg gagtagttcc 23400
gaatttatta cgcgcattaa catttgctcc tttagaaatt aataacttta caaaatcata 23460
tttattacga catgagacat aatgaagagg tgtatatcta ttaaagtcta cagagtctat 23520
attagcattc tctaaacata tctcaaacaa ttccacgttg ttgatatcgt gtttacataa 23580
taggataaaa ggtgtgtttc cgtacgtatc ttttttatct acatctgatc cattatttaa 23640
caatatctta attaattcat tgtatgattc tgattctgat tctgatttct tatagtgata 23700
tatacatcta tgtaataatg tacaaccgta actgtcttcg gcatctatat aaaatacata 23760
tatagatatt aactgtatct gatatatagg acaaaaaatg tcttgttcta cgtccatttt 23820
caagcattag tcttatccta ttatctggat gatcattatt aactaattga tatacatatt 23880
cttttatatt aatggatgat gataacctga gattgtgtat aaatgacccg ttcttattaa 23940
tatttaatac tctatctaga aaaaaaatta taatattcgt attagcatca tccatagaat 24000
aaatatgtag aatattttcc ccatattcta aaatatggaa taaatttggc aacctagata 24060
aaaaatcaac tattgtttta tccactttct cgtatgttcg aacgagatta taatcctgta 24120
ttatatggga tgtggaaaaa ttggaaaaca cgcgtgctat ataatgaaga gataaatata 24180
cactccagtc aagtatttcc tttttaaaaa aaatccatat ataatttata ttctgtaaca 24240
tgttatccct tttcaattaa caatgttggt ttataaaaaa ttaaagaagc gaatcaatga 24300
ttaatagatg ttaagaacta taattacgat gtattaatag gtatagttag ttagttaaaa 24360
agagataaca gttactaatt aattgttagt tattgtctat atgatattac aacctattat 24420
ttgttctcta tagttacatt aattaaaatt ttatatgtga cacctattca tctggagaat 24480
acttcttgat accatgattc tggccaatct gcaaacacag cacaacagca tctttccact 24540
ttgatagcgc acacgtatgt cgaggtagcc tcatccccag gtttatatac cttgatgaat 24600
cgacacgtgt acttgatgtc ctctttcttc tcacagaaat acacaacaca aagtcttttg 24660
atatgctttt ctatatcatt ctctatcagt ctgaggtagt cgtaacccac cgtgaatcca 24720
aatactttgt gtgtattatt atcaactcca atgaacaaat atccaccctc tgtgttggca 24780
aaagatgaga gtatacgtgt tcttagttgc ttagctgaaa cagatgtatg tttaacatta 24840
atagatttac cagcctgaag ttctgatcta ttgaagaact cctctaccaa tctctcaatt 24900
gattcagtgt cttccactcc atctggatat tcaaattcct gcatttctgg tctgggactc 24960
catccacctg attccttcag ttcgctaaga tactcatttg aatgcatgat cccatagtct 25020
tcatgtacaa atttgttttt acagtactcg gtataagatt ttgattagac aaatgcgtat 25080
gcacataaca gcattcttta ccattcacaa tatcaaaatg atcatataca acagaccaca 25140
tatggcgtat agattccaaa cgtttcatga gtacatgatt cacactgtct tccagagagg 25200
tggttacctc gatggtgccg ccgatatagt agaagaaaga ttttctgtat cattctcccc 25260
aagtttaact tttaccagat ttgggatcgg aagcaccgca ccctttttga atctcattct 25320
cataatttcc tttccatgta cgtccacagc agtaacttga cagatacaat ctcctatcca 25380
gacgtggtaa tcgatgatag gtcctgaact gagtgcattc atttctttgg ccttctcttt 25440
gatagtagaa taatcatgtt gaacttttcc atatacagcg ttttctgttt caagtacgtg 25500
atgatgaatc cctactcctt ccaaacacaa gtctagactc tcgtacccga ttccgcttag 25560
agcatagtag tttttgtggc gatatgtgat ttccttcttg atcatggatc ggatctccaa 25620
tttgtagata ttcattgcac tcaaacatag gcagcagtgc tccaatatat ctcttgttca 25680
cctgactgta acaccacata tatttgtctt ttacaatgtc atacttgtta ttataaactg 25740
acatcattgg caacagtcga tgatattcca ggaaaggcat gaagattctc gtcgtaccca 25800
ccgagagcgt gtgcgtaaaa catcgccatg atttcggttg tacacacgag atcaataata 25860
aattaagtta ttttttaatt tttatcgaca aaaattttac atcaaccaaa caccacactt 25920
aataatatac accctgcatt aatatgtgcc gaaacttgtc gtaattgggt tcctcaaaat 25980
atgtcaaaga gtttaccatg gtaatatatt gcagcaattc tctaggtgca tattgcaaac 26040
tggtcattaa caaagtcgca gtattgttaa catatttctg ttttgtggca cttactaatg 26100
cacaattctt tgtttcagat atcttagtcc atggcaagat acctcccaac catctaatca 26160
tacaatatcc aagtgtttct agatctccac gtctagatac aacgtatcct ttatgcgaat 26220
ctataggtgt aaattctaga gtaccgttat ccattttatt tggatttctt ataaatggaa 26280
catgttcgcc attagacatg aatttagaaa ccaatccgta atccactaga tataatttat 26340
tcttatctat ttgatccaag actatattac tcgctttaat atctccgtga gaatatcctt 26400
gctcgtgcat aaattgtatg gtatttaaga tttcgattcc gatcaacatc accgaccttt 26460
ttggtaatct attattattg gctctgatca ccgcatctag atctgcacct aatctattaa 26520
ttaccaagaa tcgatattcc acattaatgg atttgtatag accaaatgcc ttgcacgtga 26580
taagacctac gtgctttata ttgtgagatt ttttccattc ttcgataacg gatggtttaa 26640
gtactctagt ataaaatgcc tgttcggtaa ataatgatcc gttagctttg ggctctattt 26700
ttactacata attattgtca ttagtagtat aaatactacc aaatccacct tttcctatta 26760
atggtccaac gacccattga tttttgcaat tgtcagttaa cacaagtcct tgaaagttca 26820
taatgtgtga tctatctgtc aatgaaatat cattttaaat tttaagtttt acgtggtaag 26880
ttttaatatt taactaatac attagacgtt gaaatagcca catataaaaa cgagttatat 26940
tattaattat caagttttaa gtcttaagtc tctaattagt gttaaaatac attctaatac 27000
ggtcctgtag tatctgaatt aacttactat atgctaaatt cacatcatct tcaatgataa 27060
tagtgtcgaa tagaccggct tcacctgcct catccatgtc agtttttgcc aacatcacac 27120
gacgatgaat ctcatcatcc gcttcagtgt ttctacaacg aagcttggtc tcaaccattt 27180
taagagaggt aggtcttata tacaccgagt aaggcattag gtaagtattt ttaaaacttc 27240
taacaccgtc gatgtttaga tccatcacac aaatacgatt attaatagcc gctgtattca 27300
cagcagtttt agaagttccg taaatatttc ctaaaaactc agtatgttcc ggcggctatt 27360
cccttccaga tggcctctct gttaacgtaa tggtaatcga caccttctcg ttccatagga 27420
cgaggaaatc tagtggtatg ggacaccaca aatccaaata tattcccata gtcttttggc 27480
tatggctgtc tttcctaaac cagatggccc gctcaatatg atagatttta ctatcccaga 27540
catttatgta agtcaaaaat ctagactttg ttctctgttt tgtatttacg tgaacgttta 27600
ttatatatat aatatgtaat acagaatatt gccacggccg acaatataat taatgcggta 27660
ataccaaata tttctacaaa gtccttggtt ttataattgc taatagaggt tgtactaccg 27720
cctacagtag ttgatggtac tgtatcatta tcattgtacg tatcataaag atccgcatca 27780
tcggtggttg atttagtagt gacaattcca gatgatgtac ttactgtagt gtatgagaca 27840
gtgtctgtaa ctgtatgatc ttcttcttta tcagtaattg gttccggagt ctcgtctgtt 27900
gtggattctc cagatgatgc acttactgta ttaatgctat cactagtgta tgtgacggtg 27960
tctgtatgat cttctacatt atcagtaatt ggttccggag tcgcgatttc gaataccgac 28020
gagcaattag aattatctat ataatcaggt ttctcagaac tagtttccgg tgaatgtgta 28080
gatccagata gtattatgtc tatagtcgat tcactatctg tatttacaat caactctgtg 28140
gagtattctt cataatctac tttatcagtg tcatttgtag gcgatgtcat aaagaatgca 28200
catacataag taccggcatc tctagcagtc aatgatttaa ttgtgatagt tgtaactaga 28260
tcatcgtatg gagagtcgta agatatttta tccttggtat aattatcaaa atacaagacg 28320
tcgcttttag cagctaaaag aataatggaa ttgggctcct tataccaagc actcataaca 28380
acgtagtcat ttgtattatt tcgattacat gataaagttg catcatcacc tattttttta 28440
gatgtctgag gaaaaggtgt agcgtatact aatgatatta gtaacaaaag tattggtaat 28500
cgtgtcatat tagtataaaa agtgatttat ttttacaaaa ttatgtattt tgttctatca 28560
actacctata aaactttcca aataccagcc accgaaagag caatcttaat catgtcaggt 28620
tcatatttcc ccaacatact agatccaaat tcgcctacat caggtaaatt catcataata 28680
caatgtctgt tcatatcaca cgatgatcca ttgagcatct catctctatc aagaatccta 28740
atctgtggtt caaaataaca gcatctacac tcatcgttaa ttgtagtatt gtctaatata 28800
tttttgctaa tatttgcgta agttctatta tcagctattg catgcatcac agatccatca 28860
acaaccatat ataatataga acaatagtcg gactttatac ttatgtaaaa cttgaaccaa 28920
ttggaactcg gaagctcgtc atgtagacgc tggtgtctag atataataac attattatcg 28980
gttacacttc ttaagagagg tgccgcatcg atagagaaat caaacaggag aataatcaat 29040
gatgcatttc ctttggtaaa aaaggaaaca tccatgggaa gaatggctac tttatatgaa 29100
tttaactcta tacacgcaca cgctttatca gatgagatta atagttcaca aacatctcta 29160
tcctttccta tggatataat aacaggaatg gcatctttag gtttaaaata attatataca 29220
ccagtaggag tcttgtcatc gtcatctatc tttatcaaat tagcaaatct ggatattctt 29280
gatacattct ttttatacag tgaattgcat acatcggata ccgcattatc catatatggc 29340
aaatctgcaa tcactgtatt gtttttagat tgtccgccaa tgtgaacgtt cttgactttt 29400
tcacaacatg gtttaatcat gaaatcattt tttatatgat ttatttcctc gccatgtttt 29460
actaacgcgt ttagacagta tacaataaca ccatccatgg cgaccaccaa ctaaatagtg 29520
ttattttaat ttgtatgtaa ctattaagat ttagtcaagt ttactaaatc gtttagatga 29580
gtagattctt tccacgtttt atcctctctt atcctagtaa atctaggaaa tctaatggat 29640
attccatttg cggtatggga cttggaagat gtaaactctg ctcctgaaat ttcccatatc 29700
tgagattgtt ttggatcctc tactacaaaa tcgggaatat agattttatt aactactaac 29760
cactctggaa tttttttggg atccttgtta attttaatca tctttaattg gtcttgcaac 29820
tcccttaacg tattatcatc gtgtcctgaa cacttggtaa ccgtcttcca tttaccggat 29880
tcatcgtcgt aacaacccat tagaaagact gccatgatac caccctttgc tcctttacca 29940
tagtaagcac ctagtactac taaatcggca gaatctgcca tggaaccctc gttcaaatag 30000
tctcgcttta tttttaacca tcttctcttt cccggttcgt atactccatt aatatctttt 30060
aagaccaatc cttctaattt tctcgttagt gcatcatcca atacgtcagt taactgagac 30120
tcgttactaa tattcgtcaa ctctgagaat actattctat tgggtatttc aaccataaca 30180
tctttgagaa aagatcttcg ttcgtacaat ggaatgtccg tcatatcgaa tccatcaaag 30240
tacaaacagt caaacacgaa caaacacatg ttagagtttt tatattcttt ctttttgtgt 30300
atacctaaac ttccaaacgg gagcggtaca ttatgttcgt ctacaagaac aatttcagaa 30360
tccaatacga tagacgtagc ttttttaaat gctttcggta tgtattcttt gagataatcc 30420
actttatgag agagtactgg tttcatgttt ctactaaaga aggcaaactc gttattattt 30480
ttatgaactt gtactctttc accatcgtat ttgacttccg caaacattcc tgatggaaat 30540
tttttaaacg ccttattgac agaatcacac gattccgcta acatgggatt aattggagtc 30600
ataacagaaa tagatataga gtctagattt tgtttagatg cattttctat tatctctttc 30660
aagttattag attttctaaa cacatcatag gcatgaggac taatagcgtt aagtacgtac 30720
cgagggcccg ctttaatttt tagatcttta tcaataagca tgactacaca ttttaaatca 30780
ttacatgtac aaacggatgc gatatcagtc aataatttta tttgatgcga ttctttagtt 30840
acggatgata acgtagttaa aaaactatcc acttcttcta aagttaaaat gcttttatct 30900
cgtggacgga tttctgtgtt ctctttgaag aaagtcctaa tagtgtctcc tatatatccg 30960
tatcctaaat cttgtagcat atcttcctga gattgtttaa atattatact atataatttt 31020
ataatttgtt tatcgttcat gttataaatt ctatcgtcta atccgggaag caatagctta 31080
atgatcaaat atttatcatc cctatctgtt ataaagtctc taattaattt agatttttct 31140
ttatatcctg atgcgtgata tatatcacag cataattttc taaattcgcg aagcgacgtc 31200
atttaataaa aaaagtattt ttttttaata ttttcacaaa tatcgttcgc ggatattatt 31260
agacaattgt agtatattct cacgtatcac ttgtttaata tctatatccg ctattctgga 31320
accgagtact tcggcatacg tagttttaaa atctggatta ttcattatat attttagagt 31380
aatgatagca tctactatat tttctaggtt atccttataa aagctcataa acttgttaac 31440
tatacaatcg ataatttcat tgtcgtctaa tgaattaatc aattcggtct gatagatctc 31500
ttgatctata atagtatata cagtatctag gaaagagata aatggattat ccaagtttga 31560
tctacacatg ataaaattta caatgtcctt gtttaatata tcattatcta tagtttctat 31620
cttggcaata actaattgag atattgatgc gagttcggta tgcatatcgg acacgtatcc 31680
gagtactgat tccaagttgc cagagtaata tgcttcatcc atttataaaa aatgtaattt 31740
cactattaca tccacagttg ccccactggt ccagtaaccg tgtgtatagc ctctataact 31800
atattcttaa tcaactcctt ctttacatct tcctcgaatt cagaagaaat aatttgccaa 31860
tgaatatctc cttcttcaat cattttttta tattcttgta ataccttttg ttggaatgta 31920
acatcttcat aaatttcctc gccgacgttt ctattaattt ctttgctacc agattccaag 31980
aatataacta agtcgggttt aggcaatcca gattcataac tcttactgag agtcattgac 32040
gcgcctttag cggcggcata cgctactcca gagaatgcgt atctatcaac tattaaagta 32100
attccctgtt ctagttgttc ttgtataaaa gatgcaaact cccatctatt tgcacaaaat 32160
aatagattaa ctatatgatc attataggtt tttttacgag ttagatagtc atctatcatc 32220
tttccagtga cagtggatct ctgaggaaag ttaagatatt ttatcgtgtt tgccggtata 32280
gattccatga tgttcataca ttgtgttgtt tttccagatt tgtccaatcc ttcaaaaacg 32340
attaatgccc cacgagacat ttttgtaaac ctaacatatt ttttacaatt tatgcgtata 32400
ataaaactga aaataaatat atggtcatcc gagacgatta ggtctacctt tatagatcat 32460
gggtaacaaa aatattaaac catctaagga aaatagactg tccatcttgt ccaaggataa 32520
gatggattca tttaagagag gatcctttag agaaaagtcg cgtgcaacca tccaaagatt 32580
ttcatctctt agacgagaac atattaaagt agaccatcct gacaagttcc tggagttaaa 32640
gagagggata tatgaaataa ttcagaaatc gtcgtctata gatgtggaca aacggactaa 32700
gctcatgtcc aacataaaaa cgatgatgat aaatccattc atgatcgagg gtttaatgac 32760
atctttagaa aacttggatc ccgataacaa gatgagctac tcatcggtga tgatattggg 32820
agaattcgac atcatcaata taagcgacaa tgaggcggca ttcgagttca taaacagtct 32880
gttgaaatct cttctcttgg aatactccat tagtaatgac ttgttgtatg cccacataaa 32940
tgcgttggag tatatcataa aaaatacatt taatgttcca gaacggcaac tgattctgag 33000
aggtcaatac ctaactccaa ttttcagtga tttgttaaag tatgcgggtc taaccataaa 33060
gtcaaacata cttatgtgga ataaacagtt tatcaaacca gtatctgacc tctatacatc 33120
tataagactc cttcattgtg ttacagaatc atataaggtg attggaatgg gataaataca 33180
acaattatat tttttatcat atccttcacg ctataaaaaa aattatacat ccgtttccct 33240
gtcggttacg gcagaacatg tagacgaatc atcgtcttca aaataatcaa attcatcctc 33300
tatgctctca gtgtgcccgc gtagatactt acatagattg tatcgtagtc tagatagctc 33360
agatattgga atactatcag atatatgttc ggctaatgcc atacacctat attttttatt 33420
tgtcaattcc caatgtttag atactagact agatagagct actactattc tagaatcaca 33480
acatatcata tcctttacaa agttgacaaa gtcaaatagt cccgaatcgg agtctacttt 33540
aagtttctca ttaaataata gatcaatgtc tccatactgt ttaatagcca aatcatctag 33600
tgtcatcaat gccgaataaa tattgccgga tatagtattt ctgtgtctta tatattctgc 33660
taaaatcagt ttaaaactat acttattata caagtaagtc atactaaccg gcgtattaac 33720
cgcgcaacca atattagttt cctctggaag cacccctctt atctctatgg agtcattatg 33780
tctattatat gaaataaacg tgtcaactac tttgtcccta tcaaattcga cagtgtagtg 33840
tgtatcatta acttcattac gtatgactaa tttattttgc tgagtagaaa agtaaactaa 33900
tgcatttatt gttttagacg cattaactga tatatcaaac gccattctcg ttaattgtaa 33960
gaaaatgtat tatcttttca tttatgtaag aaataccaat aactccacac gctaatctct 34020
gatcattttt tgaaatagat aacgcctttc caataattgt agatatattt acatctgtat 34080
ctaaataaac atatgctaca ccatatctgt ttacaaagat gttaccgata aatatttctg 34140
gactgcctat ggaatcacat ccttgactaa tatctccgta acgatgaatt atcaaactat 34200
acgttccgga ttttaatcca ataactttat cttttccatg gactggttca aagtaaataa 34260
ctcctctgat attatcgtgg tctattatac aaacagccat tatttagtaa aatagaataa 34320
gtagtctgat attatgagtg gcagcaatgg ccgtgtacgc ggttactggt ggtgccggat 34380
ttctaggcag gtatatagta aaactgttaa ttagtgcaga tgatgttcaa gaaatcagag 34440
tcatagatat tgtagaagat ccacaaccaa taacctcgaa agttaaggtt ataaactata 34500
tacaatgtga tataaacgac tttgataagg taagagaagc gctagatggg gtaaatctga 34560
ttattcatac agctgctcta gtggatgtat ttggaaaata caccgataat gaaatcatga 34620
aagtaaacta ttatggaaca cagactatat tggcagcttg tgtggaccta ggaatcaagt 34680
atttgatcta tactagtagc atggaagcaa taggacccaa taaacacggt gatccattca 34740
tcggccatga gcataccctt tatgatatat caccaggaca tgtatacgca aaaagtaaac 34800
gtatggccga gcaactggtt atgaaagcca ataattccgt aatcatgaat ggagcaaaat 34860
tgtatacttg ttgcctaaga cccactggaa tttacggaga aggagacaaa ttgatgaaag 34920
tcttttacga gcaatgtaag caacacggta acattatgta tcgtacagtc gatgataacg 34980
cggtacatag ccgggtatat gtaggaaatg ctgcatggat gcacgtgttg gctgcaaaat 35040
atatccagta tccgggatct gagattaaag gaaatgctta cttttgctac gattactctc 35100
catcgtgttc gtacgatatg tttaatcttc tattgatgaa accattggga atagaacaag 35160
gatctaggat tccaagatgg atgctaaaaa tgtacgcgtg caagaatgat atgaagagaa 35220
ttctatttag aaaaccatca ctactcaaca actatacgtt gaagatatcc aacactacat 35280
ttgaggtgcg taccaacaat gcagaactag atttcaacta ctcccctatc tttaacgtcg 35340
atgtggcatt cgaacgaaca cggaaatggc tagaagaatc agaataagta ttttttttta 35400
aaaaaataat cgagtagggt atcaccacta cacagtaaga gtacagtaaa taaaaagtat 35460
ttatatactt atttttatag atcgtattat gcgctttcta catccatatc atcgtcatct 35520
tcaatatcga taatattttt ttcttctacc ttgacatctt ttgcctcttc gacagcaact 35580
gattgcgcta ataatacatc cttttctttt ttctttttag gtgtgacatc aatagttatc 35640
ttttccaagt tatacgatat ggtaacaaca ttaccaattt ttgaatcaac cgtaattttg 35700
attttatcca tttctaatag catagcataa ttaagagttc atttttattt ttttaaacac 35760
gtatatggtc actatcaatg tagacgctat tagcatacat attgcagtaa aatcatagat 35820
gtcatttata tctttatacc atataataga atcgtatcct attatagtaa tacacgtgga 35880
ccgatgtaga gaataagtct tatgtttaga tgttaatata gtagatgtac tcgttgccaa 35940
atttttaatg agacacgata catttactga gcattgtata tcattatatt ttaagtttcc 36000
tgataatgag acaatcaaac taggattaag tgaaccatat ttgtgtttta aaaaataacc 36060
atgtgtaaaa aagacattat cgtctagttc atctacggtt aacgtgcgat taataaaatt 36120
atatctatat ggaatatgcg gattatattt tatatttact acattataga tcctatcaaa 36180
atacaaatgc ccataacata attccacatc ctctgaatga aatctaaaaa tcgatgaact 36240
gtatgccaat accggcatta ttgacatcgt caatatggat attatccatt tcatcatcat 36300
catttaaaat tgacactaca tatgaatatt actttttatt ttaattacca gttgcacgta 36360
cacgggtagc gtgatctcta cacgttctat acacgtcacg tctggatgtt gttggcttac 36420
ccatcaaaaa tataagtgcg gtatgagttc tcgctataac gatcggagat acaggggcgt 36480
acccagtaag caactccata gcatacgtgt tctcatccat tagagagtta gtatatacaa 36540
tacaatattt ctgaccaata agaggtttta gaatattacg attagtgatg agaggattaa 36600
tcttggcaaa tgttctgtta ggaatagcag ctagaacatt ctttgtagtc ttgtaatcaa 36660
cgatggcggc atcctcgaac ttattatttt ttgagatatc ctcgataatt ttatgccatt 36720
cagccattgt tatttattat atatgttttt taataagaca tctattggaa taaacttgac 36780
attagcattc tattcttact acaaaatata aaatataaaa taaaatatac aatccaatac 36840
tcacataatc caactcactc gaacactatt tttccaatta cgataacaat attgcagaat 36900
gtactcgtta ttatttatta ttttgatgtg tataccattt agttttcaaa cagtgtatga 36960
tgataaatcg gtatgcgatt ctgacaataa agaatatatg ggaatcgaag tttacgtaga 37020
agcaacacta gacgaacacc tcagacaaac aacgtgtgaa tccgaaatcc ataaatatgg 37080
cgcatctgta tcaaacggag gattaaatat ttctgttgat ttattaaact gttttcttaa 37140
ttttcataca gttggtgtat acactaatcg cgataccgta tacgcgaagt ttgctagttt 37200
ggatccatgg actacggaac ctataaattc tatgacccat gacgatctag taaaattaac 37260
agaagaatgt atagtggaca tttatttaaa atgtgaagtg gataaaacaa aggatttcat 37320
gaaaactaat ggcaatagat taaaaccaag agactttaaa actgttcctc cttctgatgt 37380
aggaagcatg atagaactac agtctgacta ttgcgtaaac gatgtgactg catacgtcaa 37440
aatatacgat gagtgcggaa acattaaaca gcattccatt ccaacactaa gagattattt 37500
taccaccaag aatggtcaac cacgtaaaat attaaagaaa aaatttgata attgttaatt 37560
gttattttta taaaaacaag aacggtacgg cgatatttat ttttttctaa aacatctaac 37620
cgaagtagtg gtatgataaa aatgtagttt gggagtattc gttgtactac aaatatattt 37680
ccgtttttta gttccattct tcgtggcatt tttagctata aaattatatg gggttgtctg 37740
gtttaatatt tcggattctc ctacccaata tccgcgtcta atgcttctta aaaaacttaa 37800
ctcgtttgga gtctctatct taattagatc cgaatttgga tttagagctt tgcatgcatt 37860
acgtccttcc tcccaggttt ttcgatcagt agataaatgg atacatttat tattatagct 37920
tatccagtca gtaggacaat cttctctaat atatgcatct tttatcgttt tatctattga 37980
tggtgtatga actaatttac gttctacaac ttttaatagt gtcgctgtaa aaataattcc 38040
aacaattaga ccgcatatta cgcagcaagc ataaccagca taatctgtct tatgtttgtt 38100
cattgtcgtg cggtgtactc gattaagatt acattttaag tatttttttc atttgtggca 38160
ttcctactcc tatccctata tctgctataa ataacggttt cgaagttacc attactgaaa 38220
atagtcgcgc atcgacttgc gagctacgag tttgtttaga ttttgtatcg aacgaatata 38280
tagaattttc ttttatgaag tatattctat attcccgatg ttcattttcc ttctccttta 38340
tatcgaacca tttaacacca gacggtcctt cgaagatagg ttggttagat aaaggcttta 38400
taatatcatc tagtacatta tatttttcta tgacttcaaa cgtggtatgt ggaacaactt 38460
ttccagctgg taaacatata ccaggagctg gagacggcaa ttgctttgta tatccttcca 38520
attttgacgt agaaaaagat tgtttaatgg tattcataga ataggtacat aatgcggact 38580
tggaataagg actatcgaag aatacatata gtatcgtatc attatctgtt tttatagttc 38640
tagaatgaat aatttgtcta taacttcttc cgtcgatatc acattctaat tcgactttga 38700
gaaacgtcga ccatctatga ctagacaatg atgatggacc accttcgtcg tttaggcaca 38760
tttgtgctat atacggaatt ttgacaattc tctttgagcc gatagtatca gtgaaaagaa 38820
tgtaaacttt gtcataagta ccatctttat cgacgaatgc tcctcgtaaa ccatcttttg 38880
gaattacgtt atccgccgtg tataaatcat aaccacatgg tccgtcaaat cttctccatc 38940
gtttaattcc ttcttttgat atgtttatgt cagatagtac acatccgttg tgactgatta 39000
tcgttacttt gctattttga taaggagcgt atcctctacc tctatgtttt gggtcgtctg 39060
aaccgtctat tttccaacat ttgggatttc cgttattggt tccgcatcct ctacttttat 39120
agatgttgtt atataattat tattagttaa accagttttg tttagtttat tatttgaaaa 39180
tgtgtatacc gccccattaa cacccgtgta taatacgtcg tctaataagt aagtagaaat 39240
tatttcttca ctcgtttcaa acttatgcca ttcaataccg ttagcaaaat agaataaaat 39300
aaataacaaa ggtatcattt taaataaata aaaaatgtca agagttagaa tatcgttgat 39360
atacctctat acgttggttg ttataacaac tacaaagacc atagagtata cagcatgtaa 39420
tgataccatc attattccgt gtactataga taatccgaca aagtatatta gatggaaatt 39480
ggataaccat gatattttaa cttataataa aacttccaag acgacaatat taagtaaatg 39540
gcatactagt gctagacttc attcgttatc agatagtgat gtctcattga ttatggaata 39600
taaagatatc ttaccaggta cttatacatg cggggataat actggaataa aatctactgt 39660
gaaattagtt caacttcata ctaattggtt taatgattac caaacaatgt tgatgtttat 39720
ctttacgggc attactttat tcttattatt tctcgagatc acttatacat cgatatccgt 39780
tgtattttct actaatttag gaatcttaca agtatttggt tgtgttattg ccatgataga 39840
gttatgcgga gcatttttgt tttatccgtc aatgtttact ctccggcata ttattggatt 39900
gttgatgatg acgttaccat ctatatttct tataattact aaagtatttt cattttggtt 39960
actgtgtaaa tcatcatgcg ctgtacacct cattatctac tatcaattgg ccggatacat 40020
tttaacggtt ttgggtttgg gattgagttt aaaggaatgt gttgatggta ctctgttatt 40080
atctgggttg ggaactatta tggtgtctga acattttagc ctgttatttc tagtctgctt 40140
tccgtcaacg caaagagact attactaggc atgtgtataa taccacgagc tagtagacgt 40200
ggaagaggaa ccaggaacta ttgttatttt ataataatcc ttgatcttat tcttattctt 40260
tttatcagat tttttgcttc cagttttatc agtagatata caacagagtt tcataaaaag 40320
agaagagaat gaatccattc cgtacagtat ttgataatag cttttttttc gttttatgag 40380
gtatttagag attagagatg attaatgatc cccatactag aaatctatta atccacagaa 40440
atactaatgc tcatatttat attatcaatt ctaccgtaca atatttgttc cttgataggt 40500
acagaattgt acgactgcat ttttttgtat actaagtcga atggatgctc gaggttacaa 40560
acatgtatta aagtatcttg ctcgatgcta gaatttatgt acttggcaga ggacatacct 40620
atacagtttg atggaatagg aaactgctta ttgtcgatgg ttataatgga ataccactta 40680
ttattcgcaa atatctgatc gcatatgtgt ctatccaaat agtcggtaac tcgtctaata 40740
atgaatacag acaacggcga ataattaatc agtgatagat tgtttacata cagtatgtcg 40800
tttgtaaacg atgttaccaa tcgtttgcta ggtatatccg ctttaacaac caatatggtt 40860
gtaggaccct tgctaactac gacacattta ctcagtgggg atatgattac agcatgatca 40920
atgggaaagg ttagaatatt tttgccattg acgtcattat ctatagagat aacacatcct 40980
ccgacagaac taatacagag tataatcgtc gataatctat gaggaataag atggtacatc 41040
tcattgtcat ttacaacttc tacgcttaag atgttggtaa gaagtaccgt ttcatccatc 41100
tgtctattga tctcatcaga tataattttt tgatgttctg tatctatata atatctacag 41160
tcattattag caataaaatt gctaatttta gaaatgccga atacagggaa tatctccatt 41220
tgtacaacgt gacggcagca ataatactaa atattacttc aattttataa aaaggaaact 41280
aatcacacca atgattctat atcatcgtgt tcatgatctt gttcttgctt attaagataa 41340
tcatcgctat gtgctcgtct aaacggatta ttctcactaa atttattgtt gagttctgta 41400
atgaacggat ttgacttgct acaaatactg gttttattat aatttacgaa aggattggat 41460
gaatagttag gattctgttt ggtatcttca ttaagtacta ctgtagtgtt ctgataaata 41520
gtctgttcat tacgatcatt atttattagc agcgtgcttc cagcaacact atcgtaaatg 41580
tgttctgtgc taggcgccat aacattggat tcgttatccc atattaaact accagcgaag 41640
ctatcatcgt ccaatatctc attcctagaa atattatcta cgtcattgtt ttgttccata 41700
gcactacagt gatcctccca gtctgattcg ctatcagttg atttactaga tttgctggaa 41760
ttagaactct ttatcttttt taattttgtc atgataattt tattgtcatt atagacagta 41820
cgtatctttt tcctacaaat atataatata taacatacta atattgttcc cgcaactacg 41880
gtcaccgtga taagaggtac cagcatcatt tctgattgct caatatacgt actactagtt 41940
caatatttat tgttttatta tttactttac aacttttatg ataaaaaatt actattgcat 42000
ttcccatcaa ttatgatcca tccattgccg tctgatatgc agaatgaaga attaaacgac 42060
aatttcattt tcagattatc tgaaggattg atgattagat gataatctcc agctgtatac 42120
aggttatacg cttctatgat tgtagcgtta aaaacatcaa tagatgggaa tagataaaat 42180
ggctgatgtt tatcttctat atctaacatg atatcatagt cgcatgctat gatgatggta 42240
ttttttgatc tgtatgcggc acaaatgcta taaatgttga atctagccaa atcattagaa 42300
tcctgaggaa ctattttacc cttatagcta aagtagcatt tttgcatgtc ggaatatttt 42360
atatcccgta catctatttg gacagttttt atgttaccta taatgtatgg tcctataaag 42420
tccatgattg agatatcgag atcatcatac aatgtatctg ttatagtcaa cacacccatt 42480
ggagtaataa caaacgcggc gtccatggcg gcgtacgtta acgacttatt attaattcat 42540
tttttgttgt cacttgtaga attttttaac acatagtaca gattgagtac ttttacatac 42600
tgttttaacc agttttccag acttgtatat ataacacgct tcagcatccg tcgtactgtt 42660
tagttgttta aaatttgtta atttactaat atctatatct ttatcattat taatatctaa 42720
ccatttatca ttggtctttt ttaaacttac ccaataatct ttataaaaaa tactaaacaa 42780
tactctcaga tgtctagtat ccggtctagg caatctggct cgtaatttac gacactgata 42840
aaccgcatta tctgtagaca ttttaatgtt agtatctaaa taacaatgtt tatcgtattg 42900
tatccatcca ttggcgcaag cactaggcat cagttcttct ttgtaatgca gaaatgttcc 42960
tatgccacta ataatggttg agagtatcat cattatagcg accggcaccg acaacttctt 43020
aaacctactt acagtttgtc tattaagcga tttcatttat taatgtacaa aaataaatat 43080
tagttcattg ttttaacaca aaaatacttt ctaacttctt gtgatacatc agaatcttga 43140
taatcggatg tagtttttgt aattggatta ccatcagatc cccatgtatc cttaacataa 43200
tcaatgagcc aggtagtcaa gacatcggat ttattgggta gtgttgatga ttccgcagtg 43260
caatttgctt tagcatccga gaataactgg tagtctgaat gtaatatata acaagaaccc 43320
tggtaatata aaccattaca gctttctttg tgatcatatt gcgtagtgct agacgcaacc 43380
tttctatgag tagatgatgc agcagcaacg gcaacagcgg cgtcagtaat agcagcctcg 43440
ttagcagaca tgcattgatt taggcgcact atgagaaacg cggacatggt aatcatagat 43500
agtagtgaaa taaccataga tattctaata catagaccaa tcacgcgttt gcgtttattc 43560
tttccctgaa ttttgtctct gtaaacagta gcggagaaca cagatgtctg ctcttcgtcg 43620
ttttctggtg tcatcatgat aataaatgtt atttatgtca cgatgtgcct tctttgttct 43680
cctccctact aacgacctta gttttccata ttttgattta ttatcaaatt aatttagtaa 43740
ctgtaaatat aattatgaat tgtttccaag aaaaacaatt ttcaagagaa aatttattaa 43800
aaatgccgtt tagaatggtt ttaacgggag gatctggatc tggaaaaact atctatttac 43860
tatctctgtt ttctacacta gttaaaaaat ataaacatgt attcttgttt acacccgttt 43920
ataatccaga ttatgatgga tacatttggc caaatcatat taatttcgtt agtagtcagg 43980
aatctctaga atataatctg atacgaacta aaagtaacat agaaaaatgt attgctgtcg 44040
cacaaaatca taaaaaatca gcacactttt tacttatttt tgatgatgta ggcgataaac 44100
tatcaaaatg caatactcta atagaattct taaactttgg aaggcattta aacacgtcta 44160
ttattctact atgccaaact tatagacacg taccaatatt aggacgggct aacattacgc 44220
atttttgtag ttttaacatt tccatctcag acgcggaaaa tatgctacga tcgatgcctg 44280
taaaggggaa acgaaaggat atattaaaca tgttgaatat gatacagaca gctagatcca 44340
ataatcgatt ggctattatt atcgaagact ccgtattttg tgaaggtgaa ttacgtatat 44400
gtaccgatac cgccgataag gacgttatag aacaaaagtt aaacatagat attttagtaa 44460
atcaatattc gcacatgaaa aagaatctaa acgctatatt agaaagtaaa aaaacaaaat 44520
tgtgcaatag cgatcaatca tcatcgtcaa aaaatgtatc ataattataa ttattaactt 44580
ttgtaacaat agtcctattt agagaaagtc tatcgataga cgatcccaat ttgtaaattg 44640
ttccactact tgtcactcca tgatatgata aatccatgta aaatagcatc atctttagat 44700
cattaattgt taccttcccc aatacaacca aatcatcatg atatatacct cctccagaca 44760
agtatttaac aacggtagaa tgctttggct tataaaatac aaatgacatt cccttatgtt 44820
taatcttaat cttttcttta gttattgaat cgttacaatt ataaaatgat gttttttcca 44880
aaaacctaag tgtatttaaa atagatgcca tgttaaaaat gtccgccgtc gactttttgg 44940
aacgattgat aaaagctggt gtttatattt atgttttacg gacaaagtgt gtaattgcag 45000
ctttactagt aaaaaactat tccataaaag acgaataaga tacaaacaca aatgtttata 45060
taatatttaa atggaagacc ttaacgaggc aaacttctca catttattga taaatttatc 45120
taataataaa gatatcgatg cgcaatacgc gtctacatta tccgtggtac atgaattgct 45180
atccgctata aattttaaaa tatttaatat aaacaaaaag tcgaaaaaga attccaaatc 45240
aatcgaacaa catcccgtcg ttcatcatgc agcatccgcg ggaagagaat tcaatcgtcg 45300
ttgaactcga accctcattg gctacattta tcaaacaagg atttaataat ctcgtaaaat 45360
ggcccttgtt aaacattgga atagttttgt ctaatacatc taccgctgtc aatgaggaat 45420
ggctaactgc ggtagagcat attcccacca tgaagatatt ttacaaacat atacataaga 45480
tacttactag agaaatgggg tttttagtct atttgaaaag atcccaatct gaacgcgata 45540
attatataac tttatacgat tttgattatt atattataga taaggataca aattctgtaa 45600
ctatggtaga taaaccgacc gagttaaagg aaactttgtt acatgtattt caagaatatc 45660
gtttaaagag ttctcaaaca atagagctta tagcgtttag ttcaggtacg gtaataaacg 45720
aagacatagt ttcaaaatta acatttttag atgtggaggt atttaataga gaatataata 45780
atgttaaaac tatcatagat ccggattttg tatttagatc tccatttata gttatttctc 45840
ctatgggtaa actaactttc ttcgtagaag tatattcgtg gtttgatttt aaatcgtgtt 45900
tcaaagatat tatagatttc ttagaaggtg ctctaatagc caatattcat aatcacatga 45960
ttaaggtagg taattgtgac gaaacagtat cgtcttataa tccagagtct ggaatgttgt 46020
ttgttaatga cttaatgact atgaacatag tcaacttttt cggatgtaat tctaggttag 46080
aatcatacca tcggttcgat atgacaaaag tagatgttga actatttatt aaagcattgt 46140
ctgatgcgtg taaaaaaatt ttgtcagctt ctaatagatt ataaatgaac tctctatcaa 46200
ttttttttat tgtggtagct acggctgcgg tgtgtttact ttttatccag ggttactcaa 46260
tatatgaaaa ttatggcaat attaaggaat ttaatgctac tcatgcagca ttcgaatatt 46320
caaaatctat aggtggaaca ccggcattag ataggagagt tcaagatgtc aacgacacaa 46380
tttctgatgt aaagcaaaag tggagatgtg tggtttatcc aggaaacggt tttgtatccg 46440
cttccatatt tggatttcag gcagaagttg gacccaataa tactagatcc attagaaaat 46500
ttaacacgat gcaacaatgt atagacttta cattttctga tgttattaac atcaatattt 46560
ataatccatg tgttgtacca aatataaata acgcagagtg tcagtttcta aaatctgtac 46620
tttaaatgga cggaactctt ttccccggag atgacgatct tgcaattcca gcaactgaat 46680
ttttttctac aacggctgct aaaaagccag aggctaaacg cgaagcaatt gttaaagccg 46740
atgaagacga caatgaggaa actctcaaac aacggctaac taatttggaa aaaaagatta 46800
ctaatgtaac aacaaagttt gaacaaatag aaaagtgttg taaacgcaac gatgaagttc 46860
tatttaggtt ggaaaatcac gctgaaactc taagagcggc tatgatatct ctggctaaaa 46920
agattgatgt tcagactgga cggcgtccat atgagtaact taactctttt gttaattaaa 46980
agtatattca aaaaatgagt tatataaatg gcgaacatta taaatttatg gaacggaatt 47040
gtaccaacgg ttcaagatgt taatgttgcg agcattactg cgtttaaatc tatgatagat 47100
gaaacatggg ataaaaaaat cgaagcaaat acatgcatca gtagaaaaca tagaaacatt 47160
attcacgaag ttattaggga ctttatgaaa gcctatccta aaatggatga gaataaaaaa 47220
tctccattag gagccccaat gcaatggcta acacaatatt atattttaaa gaatgaatat 47280
cataagacca tgctagcgta tgataatgga tcattgaata caaaatttaa aacgttaaac 47340
atttacatga ttactaacgt gggtcaatat attttatata tagtattttg tataatatct 47400
ggtaagaatc acgatggtac tccttatata tacgattctg aaataacgag caatgataaa 47460
aatcttatta atgatcgtat caagtatgca tgtaagcaaa tattacacgg tcaattaact 47520
atagctctga gaattagaaa taaattcatg tttataggat cacccatgta tttatggttt 47580
aacgtaaacg gatcacaggt atatcacgac atatatgatc gtaatgccgg ttttcataat 47640
aaagagatag gtagactact atacgcattt atgtactatc tatctatcta taagtggtag 47700
atttttgaat gatttcgcac tattaaagtt tacgtattta ggagaatcct ggacatttag 47760
tttgagtgtt cctgaatata tattatatgg tttaggatat tctgttttcg atactattga 47820
aaaatttagc aatgatgcta tactcgttta tattagaaca aacaatagaa atggatatga 47880
ttatgtagag tttaataaaa aaggaattgc taaggtgaca gaagctaaac ccgataacga 47940
taagcgaatt catgctataa gacgcatgaa ggctgaacgt gaaatcgctc gtaaaaactg 48000
cggaggtaac ccatgcgaac gtgaagaggt tggaatatca actagatgcg gagaaagaaa 48060
aagttaagtt ctacaaaaga gaactagaac gtgatcggta tctttctagt agatatctta 48120
cctcttcttc agatccacat gagaaaccat taccaaatta tacatttcct cgcattgaag 48180
tagctccgtt gatgactgag gataaagaac cagaacctgt agaagtggtg cctccatcgt 48240
ccacagacgt taccgaaccg attagtgatg tgacaccatc ggtggatgtc gaaccagaac 48300
atcccccagc tttctgaata tcagacttca gtatcccaag tagcagttac acctccacca 48360
aaacctaaaa ctccacagat tttcgaatat cagacgtccg attctatagt taacaatcca 48420
cgcccatttt ataattcgga tctcgaattt gatgatattg atatgtatct actaccaaac 48480
tagaatatta caccagaaaa gacggtttga gatcaacttt atctaatggt ttataaaacg 48540
aaggaggcct tcgttcgaaa tctaatttaa cttttacgcc tctggcgttc atttgagtaa 48600
gaaatacttt agatacgtgc gtggtatcaa tttttgttaa gagaggagag agattaagtt 48660
ttgaacatct aagacatgta ttaataccct tgatttgtgc tgctatgtct ccacaatttt 48720
cacaaacata cacatcttga taatcttctt ccgaatcttt caaaacttct gtaatagtat 48780
tggctgcacc atgcgctatt aaacagtctc tctccatttc tccgaacttg atacctcctc 48840
cacgttttcg tccctcattc gcctgtctaa tgagcttcgt ctttttacct ctacatctaa 48900
cggttgcctt gtcctgagtt aaatgcctca gacgcaagta ataaattggt ccaaaaaata 48960
ctttggatgc ataaggctta tccgtttcag gatcatagag aatcttttca caaaagattt 49020
tatccgataa ttcttcatca gacaatttcg gatttgaatg ctcataacat tgtttagcga 49080
attgcatata tgtatcgatg gatgtttcgt tactactagg aaaacagaca ggtcggtttt 49140
ctcccttatt gttgtacggc ttagcagaat atgcggctgt taaaataacc tctatcaaca 49200
tagatatagt ttttctagag aagatggatg tagaattaat aatgacatct ggtgtgatac 49260
cattttcatc gtatggaagt tccgtttcat ccgcgatata cgcgactgtt cccttttgac 49320
tcgttctagt ggtaaatttg tctcctagaa tgggtcttct ttctttcatg gttaatactc 49380
gtaccttaac tttgtcagta agttctactt gtactcgttc aacgcgagat ttgtacatat 49440
cggtatattt ttcggaaaca tcaaagctaa tctgattatc tctagcaaaa tcatcttcaa 49500
gagttcttga tgagatattt cgtgctatag cgtctccgga ttccaagaaa gcattcagtc 49560
taactaatcc attactttct aattttgaat aggcgttaga cctatctctt tctttgttat 49620
taaagttttc caacggaatt tctacttgat gtttcttggc tgtaacaata tcgagaccgc 49680
ctctctgaat aaattgtttt ttgatgataa ttccatcctc ttgattgata cctttgtacg 49740
acattaatgc tatagtaaca tgttggccga agcaattagc cgcaatcttt gaagtttcta 49800
aagccttact aatcacgatt ggcctctctg gatacatcaa atgaattcca ttgtctattt 49860
tatttcgtat atccgagctc agacaagaga tagcttgttt agcttgagca catccaagaa 49920
tagctctggg tccagaattg tgattgattc ccactagtga agatgctaca tatccatctc 49980
taaattcggc aggaaagtca cataaatcgt attgctttct ttcatccttt gacatcattc 50040
taaatttttg aaccgattca catacgttac taaaagtaaa ttgttctata tctaccattt 50100
cgatgacatg cggaaactct ttctgaatgt cagagaatgt catgtcgtct aatctgcttt 50160
ctaactccgg acacacatcc atcatgagct ctccgttatc cacaaccaag aatggtctga 50220
ctaatcttcc cgctccaata ttaatgcgaa tttcattcat gtgatcccta actaaagtaa 50280
tacctacctc caagttaccg aagaatccca tccgttttct acgtctaaag tcagttacaa 50340
aatcacatat catatttgga ttaagagatg cgactagagc attttctata gtgattggaa 50400
atcctgtttc aaagtaactt atatcatctt tataatatga tctgatatac tcacaaattt 50460
tcttttccaa atccaaatac tcagacgtta gtatatttgt aatggaactc aagacagaca 50520
attgagatac taaacctacc tgaggacctc tttccggaac gtccgatgaa caaaagtaaa 50580
gatattgact tggatggtat tttctgacag aaaacatctt tgaaatcttt acttgatccg 50640
gataaaatcc aacactccta ggaatagaaa tattctgcat ccatgaatag tgaggatgtg 50700
ttcgataact accgtctgac tttttgaact ttccactcaa tagactagaa aatgcatgat 50760
taagtccagg agttgttagt acatgaatgt ttaccgcgta agtgcctctg ttcttgtgat 50820
tgttcatgat atcgtttcgg atgttgccta tgtaattctc taattcatca tgtgccaacg 50880
tctcaaaata tttgccgtac gttaggatgc gatgacaaac catcgaatct ctatctggat 50940
atctagaagt gtggtagata cagtagagaa actttcttag taaagatatc atataaaatc 51000
cctttagttg atcgggtgta tagttcatat gaggtaaaaa gttatgcagc atttcatatt 51060
tgaactcgtt gatcgttaac tgagattttt gtttaatgtg ttcagcttcc accaggtcat 51120
taatgtatgt atcaatatta aagtcagtaa tagattcagt aattcgttta gcactatcta 51180
ttatcgcgtt tactagatag acaacttctg gaggcatatc gtatgataaa ctacgtctaa 51240
tgaattctag actcactcta gataaatatt gagacagcaa aacaatattg accgttataa 51300
atgtctttgt cgatgatata ttcaacgctt ccaattgtga tatatccaga gatatcttgt 51360
aatggcgata tcttgtcggt aatacattag gaggggatac ggaggaaaac gagaaagtga 51420
atgagtttgg cttaacaacc ctaaattttg gccatgttgt aatcttttct actagattaa 51480
ttcctacttt ttcgacagat tgtttattga taaagactcc acctatgaca ttaggaacaa 51540
gatacttggc tgtatcaagt ggatttttat tcccgtatcc tattagtagc ggaattttta 51600
tcaaatgaga atcttttccc tcataactac ttattttagt gatggatata ccctctttgg 51660
tcattacctc tttaaagata tttacagtga acgtggctaa tgcgtcataa ctcttacctt 51720
taatactcgc gattataggt gagtaatctg gaggagtcac tttaacattg ctaatttcta 51780
tcataattcg ttctgtatta ttcttaaacg ataagagtgg ccgcttgacg gtcaagattt 51840
catgcaatcg atgcaatata aaattagaat acgatacata ttggaaatgt aacggtctat 51900
aaaaaactcc ggctttagga tcaggcacca aaaacttata tccgagtcgt tgatccattt 51960
ctgaattagt gttttttttt cattttagaa gcaattcttt tagacgatct accgattccg 52020
tttctatatc tatgctattt aaaatagtcg atctttcctt catcatttct atcatattct 52080
cggatttagt cacgtaattt atacaatcct ccagagatcg taatgctaca atattgagct 52140
ttttcccctt aaaaaacttt attttgctat cctcatctaa cagagagggg aaaacggtat 52200
gatccaacga cttaataaat gtcaggttaa acatccctat tttgaaattg ctaactccat 52260
aaacatcgtg ttcagccatt ttcttaatta ggaataattt ctcatctaat gccgtagccg 52320
tgagtacgtg gtttacaaca ttagctactt ctttaaagta ctcgttttgg atgatatcct 52380
cgaacaacag aaataaatta taatagacat agaataattt gtcaatcatg tgtatacacc 52440
ccttttcatc cttgtccttg gatagaataa tgtgcatagt agaatccttg aatattttca 52500
cacatgttct attagtaaaa ataatttcta tagtttgtaa tatagagctt tttccacgcg 52560
ttactataga gtgattaatg atatctactc tcattctctt agaaatggtt ttgatccaag 52620
gttgattaat gttggacctg actgtagtgc tcagatactc atcagacttt ttaccggaaa 52680
agtaatttgc attagtgcct ccatgtacag ttttctttat ttccccataa ttgacctttc 52740
tcttcttatt ggtagtttta atatatgata caagagatga cttttccctc tcaaatatct 52800
ctactgtacg agagctaata ttgctattat ctgagtttat atcgaaataa tgacaacatt 52860
tcacttgtga agaatcgtta aataccggat acgtattctg attaataatg tgtttagtaa 52920
gttggatgtc gcaatacact agtttcttaa tggcatgatg tatatcttta ttatacacta 52980
tattatcaaa catatcctct gaggaaatgc gttctttcat aagaccatat atatctccta 53040
tttcatcgca acttattaga tgaaagttaa aaatagttct ggcatatcta tcttctattt 53100
catgtagaaa ggtaaataga ttatccataa tggcgttact aacgttatta catttttttt 53160
atgtaatttc tagatttaca cctattataa ggtgtataat tagtattcca tttatctaat 53220
acgtatctca tagccaaatt gaaactatcc gctacatcgt ctaatttgcg tctatccgga 53280
acggagtctc gcaatccgaa tgtgtccatc caatcaagaa atgcttcgac cgatctcttt 53340
tttcgatctc tatatgaatt accagacatg acaggcgaga cgcaaataac tttggcagcc 53400
gatgtatgat ataaaaagcc tttaataaaa tagataaatt tgacgtacgg cgaccttcta 53460
ggctgacgtt ctagaagaac tgtagtgtat tcatattgtg acaaatcttt agctatgtgc 53520
ctttcccaat cagaactcca gtctaatttt gatatatcca ataccctaac ggagttatcc 53580
ttgacttcta aaacagttct ggcaggattt tttgcaccta tatcaaaggc gcatattatt 53640
tcactcgaat aatctttttt tgacatcggt gacgatatta aagattgaga cgaactggtt 53700
aaagtttcca tatatagtct caatactcgg gttatttaaa caattagtat tttcaatatt 53760
gaaatttaca accttacaat tttctatttt gaaccgcatg ttattaacta acgttataaa 53820
atccgcttct ggatatccca aacattctct gcttaaatca aatgctgatt ggttttttat 53880
ttttcgtttt acagttccgg atttattaat ctcatcaact aactcatcga cagttgcgca 53940
ctcattaata tctaatttat tagtcaattg ctttaagcct gcactaccaa ccttagagaa 54000
atactttccg ttaacataat agtctcgtcc tatagtgtct ataattcgtt ttattacttc 54060
tcctctagtt tctgttccgt ttccatcata gtcgtataaa atggaaaatg tgtttttctt 54120
ttttactttt acaaatgtat gttctctaac cttggatcgt attaaatggt ctacatcttt 54180
tactaatatc ttttttcctg attttgttat aacgctagga ataaaaatat tatctcctat 54240
acgatctacc ttgatggact caatatacat gaatgagaat ttgaaaaagt ctacaacttg 54300
ccgcctaagt tctcccaact taatatacga tatggatatt tttggaaatt tatcatcgaa 54360
agagcgttct ataatagagt ataactcgtc gtcaaataat gtgtcttcct ctatttcaat 54420
ttctaaatat ttgggtatgt ttaatccgta ctcactagct agtttaaata tattaactgg 54480
agactgatat tttgatatag catcttccat tatccatcta ttgtttaaca aaacaaatct 54540
cagaaagtct attccgttat cgctgtctaa tactttgtta cacgcacttc gcatatcatc 54600
tggtatttga aaagagtttc cagatccaag ttctaccata tttttaccct tcgaataaat 54660
aaagacgctc ccaaaatata ccggtaagaa aatgtaatag cccggatcaa tattaaacgg 54720
tttatttttt acctcatcat aataatcaga tattgacgtc tcgacattag ctaccttttg 54780
cacgcctatt ttccagtaag tagatgttcc ccattctacc aaagaattat acttttctat 54840
agccgcagaa tctgaaaatt tcaaactttt gtacagacta agtaattctt ttaagttagt 54900
taaatcagcg ctagaagtca tgataacttt atttttaatc ctatgttatt tcattcttat 54960
ttttaatatt atagtacctg caatatctga aaaaatgaga cgcgaacgag ccgcatacgt 55020
aaactacaaa cgtctaaaca agaatttcat ttgtgtcgat gatagactgt ttagttataa 55080
ttttacaaca tctggaatta aggcaaaggt ggccgttgat aacaaaaatg ttcccattcc 55140
atgttccaag ataaacgagg tcaataataa taaagatgtc gatacactat attgtgataa 55200
agatagagac gatataccag gttttgcacg atcgtgctat agggcatatt ctgacttatt 55260
ttttactacc taaatggata gcaccaatgt gcgttccgga atgaagagcc gcaaaaagaa 55320
gcccaagact acagttatcg atgacgatga tgattgcatg acgtgttctg cctgtcagtc 55380
taaattggtt aagatttccg acatcacaaa agtatcattg gattatatta atactatgag 55440
gggtaataca ctggcctgcg cagcatgcgg atcgtcgctt aaacttctta acgattttgc 55500
gagttaaata ttctatttaa tacacgttct tctctggagg atgttgtaca tacagaagtg 55560
ggatcggatt cttgatgttt ccgataactt ttttgtttaa atcctagttt atctacagac 55620
agactaataa ttcgttgaac gaaatttcct atcatgtact ttatttcttt gatggatgtg 55680
ctaggaaata catataccgt cctatctaat agttctgttt ctcgacatac cctccctagt 55740
aattgctcta tttgcatatt gttgattact gccgagcaaa tgaacaaaga atccaaacta 55800
ggaatatcta aaccagtacc ggaataaaat aaggtggata cgaatataaa tctatttagt 55860
tccttgattg atttgaccat atctggagta cgtctatttt gggcgtctcc tataaataca 55920
acctctgatc cgaaaaaatc taataatcgt ttgtagaaga ataccatatg ttcacgtagt 55980
ttagtaataa ctaaaatgcg attaatagtt cctgacttga attcttctac cagggtatta 56040
agaataagtt gatttctagg ctcgtctaca gataataact tctcggtata tatatgatat 56100
ttattagatg gtccatctaa tcgttttatc atatgtctaa tattatctgt ggaatatggc 56160
tcaaaaaaac tatctactgc atagatagtt ttttttagat cggataactt ggcaatatta 56220
ataatactgt tacaataaat tctgttagat ggtctaggtg tagcagttaa aaaataacac 56280
atcatcggag gataatacgc taaaaatctt gtaactgctg tattgttcat cagattatac 56340
gtatgtgatt catccaagat gaacaaatca taatgcttat tgatatattt acaaaaggca 56400
tcgtttgtca gatgtctact gactactatt aatacatccg gactttgagt ctttagttcc 56460
tttaatagac tacttactcc atctatggat atcttatgtt ccaatccgac tgcctctacc 56520
tgtgtcttcc attgatgtat taacatttta ttgggtacgc aaatgacggt ttttctaccg 56580
tgtgtagcca taagataaca cgtggtaata gtcttaccaa atccacacgc caagtgaaga 56640
gtgatgtata gaggacgttt tgattcgatc attttcctca tattagaaac tacttcagat 56700
acgactttgc gttgaagagg atataacttt ggcgcatttg ttggattgat actagtaatt 56760
ttattatcgg tcgttgttaa tgtttcaaat actagactcg tctttacgga aggagaggcg 56820
taaaatccct taggtatcag aaacttaaag gatgatcccg gttcaacttc tacgaaatcc 56880
ccgtcttcgt taaaaagact taggggttga ccacaagtca ttttttttag ttcggcataa 56940
agattatact ccatctttaa tagtgacatt ttttaatata taaatgagtt atttaagata 57000
ttacaatatg cttgacgact tctctgcggg tgctggagtg cttgataaag atttatttac 57060
agaggaacag cagcaatcgt ttatgcctaa agatggaggt atgatgcaaa acgattatgg 57120
aggaatgaat gattatttgg gaatcttcaa aaataatgat gttagaacgt tactcggttt 57180
gattttgttc gtcttggctc tatatagccc tcctctaatc tctatattga tgatatttat 57240
ctcatctttt ctattgcctc ttactagctt agttattacc tattgcttag taactcaaat 57300
gtatcgtgga ggtaatggca acactgtggg aatgtctatt gtatgtattg tagctgctgt 57360
aattattatg gcaatcaatg tatttacgaa ttcacagata tttaatatta tttcttacat 57420
tattttgttt attctgttct ttgcatatgt gatgaacatc gaaagacagg actatagaaa 57480
aagtataaat gtaaccattc ctgaacagta tacctgcaac aaaccttata ctgcgggaaa 57540
taaggtaaat gttgatatac caacatttaa cagtttaaat actgacgatt attaaaaatg 57600
ggggcagccg ttactcttaa tagaatcaaa atagcaccag gaatagcaga tatacgagac 57660
aaatatatgg aattaggttt taattatcct gaatataata gagctgttaa gtttgcagaa 57720
gaaagttata cgtactatta tgaaacatct ccgggagaaa ttaaacccaa gttttgtttg 57780
atagatggta tgtcgataga tcattgtagt agttttatag ttcctgaatt tgctaaacaa 57840
tatgtattaa ttcatggaga accatgtagt tctttcaaat ttcgtcctgg atcattaatc 57900
tattatcaga acgaggtaac tcctgaatat attaaggatt taaaacacgc tactgattat 57960
atagcatccg ggcaacgatg tcattttata aaaaaggatt atctcctggg cgatagtgat 58020
agcgtggcaa aatgttgttc taagacaaat accaaacact gtccaaaaat atttaataat 58080
aattacaaga cagaacattg tgatgatttc atgactggat tttgtagaaa cgatcctgga 58140
aaccccaatt gtttagaatg gttacgtgca aaacggaaac cggctatgtc tacttattcc 58200
gatatttgct ccaaacatat ggatgcgaga tattgttctg agtttattag aattattcgt 58260
cctgattatt ttacttttgg ggatacggca ttatacgtct tttgtaacga tcataaagga 58320
aatagaaatt gttggtgcgc gaattatcca aaatctaatt ccggagataa atatttagga 58380
cctagggtat gttggttaca tgagtgcacc gacgaatcta gagatagaaa atggttatat 58440
tataatcaag atgttcaaag aactagatgt aaatacgttg ggtgcacgat taacgttaac 58500
tctttagcgt taaaaaattc ccaagcggaa cttacgtcta attgtactag aactacgtcc 58560
gccgttggtg acgtacatcc aggagaacct gtagtaaaag ataaaataaa actgcctacc 58620
tggttgggcg cggccataac attggttgta atatctgtta ttttctattt tatatctatt 58680
tattcgcgta ctaaaattaa aacaaatgat ataaatgttc gtagacgata attcgttgat 58740
aatttattct acatggccca gtacattgtc cgattcatcg ggtagagtca tcgttatgcc 58800
agataataga tcattcacgt ttaaggaagg gtttaaatta gatgaatcga taaaatctat 58860
attgttggta aacccgtcgt ctatagatct attaaagatt agagtatata aacatcgcat 58920
aaaatggatg ggtgatatat tcgtattatt tgagcaagaa aatatcccac caccttttcg 58980
tctagtaaat gataagtaat tacgagccgt tgctgctgtt agttataaca tgctgtgtac 59040
tactatttaa ttttaccata tcttcgaaaa caaaaataga tattattttt gcagtacaaa 59100
ctattgtttt tatatggttt atattccact ttgttcattc ggcgatttaa aatttttatt 59160
agttaaatgg atatgatgct tatgattgga aattattttt ccggcgtgct aatcgctgga 59220
atcattcttt tgattctttc gtgtatcttc gcctttattg actttagtaa gtctaccagt 59280
cccactcgta catggaaagt attgagtatt atggcgttta tacttggtat tattatcaca 59340
gtcggaatgc taatttattc tatgtgggga aagcactgcg cgccccacag agttagcgga 59400
gtcattcata ccaatcatag cgatatttcc atgaactaaa ttattatcgt ccatatatct 59460
cgacattgtt gaatcattat tactacttat ttagtgaaaa gatgatatat tgcatacttg 59520
atcaatagtg aagttattgt caataaatga ttggtattct tttgttgatc ggtatttgcg 59580
tagcagttac cgtcgccatc ctatatgcgc tgtataataa gatcaagaac ccacaaaatc 59640
caaatccaag tccgaattta aattcgcctc ctccagaacc aaaaaatacc aagtttgtaa 59700
ataatctgga aaaggatcat attagttcat tgtataatct agttaaatct tctgcataaa 59760
taaaaatatt tttagcttct aaatggcgga taaaaaaaat ttagccgtta gaagcagtta 59820
cgatgattat atcgaaacag ttaataagat tacaccacag cttaaaaatc tactagcgca 59880
aatcggtgga gatgcagccg tcaaaggagg caacaataat cttaattctc aaacagatgt 59940
gactgccggc gcatgtgata caaaatgtat tacatgtaaa ccaaaatcaa aatcctcgtc 60000
ttcttctaca tcaacatcca agggctccaa aaatacttct ggtgctccta gacgtagaac 60060
aacagttact actacatcgt acaatgcgat ggatggtcag attgtccaag ctgttactaa 60120
tgctggtaaa atagtttatg gtaccgtcag agacggccaa ttagaagttc gtggaatggt 60180
cggagagatc aatcacgatc ttctaggtat cgactcagtt aatgctggga aaaagaaacc 60240
atctaaaaag atgcctacta ataaaaagat taatatgtcg tccggtatga gacgacagga 60300
acagattaat ccagacgatt gttgtctgga tatgggaatg tattaaatta aataatttta 60360
attcgtttaa cgaatatctt gagtataaac aatacaatat taagaaccgg actgttaccg 60420
attcctagtt ttgatgctac agcatcgcag tcatctccga tctccacatc gataatttct 60480
gaagtgatat cggtactcag tcctttgatt tcttcaaatc cgagttttag caatgcttgc 60540
tcgataatat ttatgacaat aataatcacg ttagtgacga taatttttcg ttttctactt 60600
tcgtgatatt gtttaatcgt tttatagatt ctatctattt catcctctga acaaacatcc 60660
aagtcctcga ctgataaggg agacccgttc aaatttgcat aattaacgat ggctatacgc 60720
ttattaactt ctgttgattt atacggagtc ttaccaaata gtattctggt aaaattatct 60780
aaattatcag atgattttgt attagatcgt tgatttctaa gattaaccac ttcatcctcc 60840
aacatctgaa ttcttttatc tttatcataa actactccca aggatggtgt ttgtgttggc 60900
atagaagata tcatagatct agattccatt attgcttcag catttttcga tactgtaata 60960
ttaaatcttt tttctcgttg ttgacgttgt tccgatatca ataactctct acgaaacgta 61020
ggaggtggag tatcgtcaat aatagtagta tgaggttgta ctcgttcgat aatagtggcc 61080
ggagaatcat catctggaaa tagatcttca ttaagttgtg aggatatttc ctctggagat 61140
gacactacgg cggcattatg ttctctatct accacgttgt taacgtgagt tagaatagac 61200
atttgacgaa gagttatttc ataatttttg ttagatggat aattatcttc tgaaaactct 61260
gtaattaaat cgttttgtat atccgtcact ggtacggtcg tcatttaata ctaaataaat 61320
gatgcctatt aagtcaatag ttactcttga tcaattagag gactctgaat atttatttcg 61380
tatagtttct accgttcttc cgcatctatg tctagattac aaagtatgtg accaacttaa 61440
aacaaccttc gttcatccgt tcgatatatt gcttaataac tcattaggat ccgtaactaa 61500
acaagatgag cttcaggctg ctatatccaa attgggcatt aattatttaa ttgataccac 61560
gtcacgtgaa ttaaaactgt ttaatgttac acttaacgct ggaaatatag atattattaa 61620
taccccaatt aacattagtt cggaaactaa tcctatcatt aatactcaca gcttttacga 61680
tcttccacct ttcactcaac accttcttaa tattagattg acggatacag aatacagagc 61740
tagatttatc ggtggttata ttaaaccaga tggctccgac tcaatggatg ttctagcaga 61800
aaagaaatat ccagatctta actttgataa cacttatttg tttaacatcc tctataagga 61860
tgttattaat gcaccaataa aagaattcaa ggcaaaaatt gttaacggtg tattaagcag 61920
acaagatttt gataatctta taggtgttag acaatatata acagcacaag atcgaccccg 61980
ctttgacaac gcttataaca tcgcagatgc tgctagacat tatggagtta atcttaatac 62040
attgccatta ccaaacgtag atctcactac tatgccaaca tataaacatc tcatcatgtt 62100
tgaacagtac ttcatttata catatgacag agtggatatt tattacaatg gtaacaaaat 62160
gctcttagat gatgagatta tgaacttttg tatttctatg cgatatcaat ctcttattcc 62220
tagactggta gaattctttc cagatatacc agtaaacaat aacatcgtac ttcatactcg 62280
cgatcctcaa aatgctgcag tgaatgtaac cgtggcgctt ccaaacgtgc aatttgtaga 62340
cataggtaga aaccacaaat tctttattaa tttctttaac ctgttggcga aggaacaaag 62400
atctacggct atcaaagtta ccaaatccat gttttgggac ggtatggatt acgaggaata 62460
caagtctaaa aaccttcagg acatgatgtt tataaattct acctgttatg tattcggtct 62520
ttataatcac aataatacta cttattgctc tatcctttct gatattatct ccgcagagaa 62580
aacacctatt agagtttgtt tgttacctag agtagtcgga ggtaagactg ttactaatct 62640
tatttcagaa actttgaaga gtatttcatc tatgactata cgagagtttc ccaggaaaga 62700
taaatctatc atgcatatag gactttctga gacaggattc atgagattct tccaactact 62760
caggctcatg gctgataaac ctcatgaaac ggctattaaa gaggttgtta tggcttatgt 62820
gggtataaag ttgggtgaca aaggtagtcc gtactatatt agaaaggagt cataccaaga 62880
ctttatctat ctgctatttg catcaatggg ctttaaggtg actactagaa gatccattat 62940
gggaagtaat aatatctcta tcatcagtat tagaccaaga gtaactaaac aatacatcgt 63000
cactacattg atgaaaacta gttgtagtaa aaacgaggca gaaaaattaa ttacttcagc 63060
gtttgatctt ctcaatttca tggtatcagt tagtgacttt agagattatc agagttacag 63120
acagtataga aactattgtc ctagatattt ctatgcagga tctcccgaag gagaggaaac 63180
cattatctgt gactcggaac cgataagtat cttggataga attgatactc gtggtatctt 63240
ttctgcgtat actattaatg aaatgatgga cactgatatc ttttctccag agaataaggc 63300
atttaagaat aatctgagta gatttatcga gagtggaaat attacaggag aagatatttt 63360
ctgcgcaatg ccatacaaca tcttagatag gattattaca aatgctggta cgtgtaccgt 63420
atccataggt gatatgttgg ataacattac aacccagtca gactgtaata tgactaacga 63480
aatcacagat atgataaacg cctcattgaa gaatacaatt tctaaagata ataatatgct 63540
agtcagccaa gcattggact ctgtagctaa tcgttctaaa caaacgattg gagacttgag 63600
gcaatcatcg tgtaaaatgg cattgttgtt taaaaatctt gctacatcca tctacacaat 63660
agaacgtatt ttcaatgcta aagtaggcga tgatgttaag gcatcgatgt tggagaagta 63720
taaagtattc acagatattt ccatgtcatt gtataaagac ttgatagcta tggagaatct 63780
caaagcgatg ctatacatta ttcgacgaag cggatgcaga atagacgatg cacaaattac 63840
tactgacgat ctagtcaagt cttactcatt gatccgtcct aaaattctaa gtatgataaa 63900
ctattataat gaaatgagta gaggatactt tgaacacatg aaaaaaaatc taaatatgac 63960
agatggtgac tctgtctctt ttgatgatga ataaatgtca tgttatacag ctatattaaa 64020
atctgtagga ggactggcgc tatttcaagt agccaatggc gccatagatt tatgtagaca 64080
tttctttatg tatttttgtg aacaaaagct acgaccaaat tcattttggt tcgtcgttgt 64140
tagagccatt gcaagcatga taatgtattt agtattaggc atagcattgc tgtatatttc 64200
tgaacaagat aacaagaaga atactaataa tgataaacga aatgagtcgt ctataaattc 64260
taactccagt cctaagtaaa atattttagt agcgtatcct tatcgcgttt gcttatcttg 64320
aatgaactgg tcttttttaa ctcgttgatg aattttgtaa ataattcatt tctatcttta 64380
agtaatttta ttggaagttt tgattccaca gccaatgaac atgtaaattg tgaatcattt 64440
tctatgacca gttgtaactt ttcatacact gtaatcaata cagtatttac catttgatta 64500
attacagcgc ccgtactagc actccattga acaagatcag attttagatt aattagataa 64560
aatctatatg ttatttcaga taatgaactt accagataac tctcttgacg gatattaaaa 64620
atgccagatg aatgttcatc tcgaatagcc agagctactg tagagtaata cggttcaaaa 64680
tcataaacgt gatagtttcc aaactggtat ccgagttttt cttggatgat ggatacttga 64740
gagttgaatt taaatttctt actatgttca ttatatagtt ctggaaagaa tgcttcaatc 64800
attgtttctg taagtttgca tccttttgat gcgatagtta aaagtgctat ataaggcgcc 64860
acgataatgt tatttttttt ggtaatagtg acgtctttta cagcgtcaac gcatctgaac 64920
aaataatgaa tctctctatg atctaaaaaa taaagtcttt gtaaaaagaa tcgtagtgct 64980
agttttctct catcatcctt agatctatgg gcgaatagac gtctactacg ggatataaaa 65040
ccgctatttt cctttatcat aggtgttgtt tgatctatat ttacctcccc tagttctacg 65100
gaggcctcca aattaagatc tggtactggt tcgaacattg taagacttac atcatcggta 65160
gtagattttc actttacccc acgatataaa tatgcgatat atagtaagtc cgcaattggt 65220
attacaggtg ggtaaggggc aggaggtaga acgagcccta tatctcactc catatgatta 65280
catagatgag aagtcgccca tatattattt tttacgaagt catttaaata tacaacagcc 65340
ggaaatagtt aagagacata ttctattgac gcttcgaatg actcaattaa agggatattt 65400
aggaaatttg ttagatatta aggacgatat tattatctat tctcataaga ataatttgga 65460
atatagttac gttgataata ctatttttaa tcccttcgta tatactcaga aaaaaacact 65520
actaaaaaac gatagctttt tatacaatgt atatcctgga gcgtgtgact ttttggttat 65580
ctgggtggcc agagcgtgcg atacatctat tccggaattt ggatcgtatg aagatgtaga 65640
taataatatt atcaagtttg aaacaatgtt gatggaagta tttccacaac tagatttgga 65700
cattactgta gaatcaaagt ttaacaatat atttcgtacc aatctaaaac taactgggtt 65760
aaaaaagatc attcagcgag ttcaagactt ggacattaat tataagtcgt tgttatctag 65820
atacgatgaa cactttatta atatgaccgg taatcatttt attctaaacg atgaacagtt 65880
aaatctctcc atttgggact tggatggtac attagcgtta tctagcgacg gcgataccgt 65940
gatgattaat aacgtaaaac tatttacaga tcttgtgtcc gatatagata cacaaatgga 66000
acgcatcaag ggagatataa cgtataaggt acatttggcg actcctatca attctagaat 66060
aaaattggat atcgagacta gcttcatttt tatagagacg gcgactaata atattttact 66120
atcctcggat aaaaaaatat ctatcatttt ggccaaaaac catatatcta ttaaagtgaa 66180
aaaccatatt cctaacatag aaaaatattt tacattttta gttattgcca ttaatgccat 66240
gtttaatagc gttcaaaagt ctgctgattt taccaaagtg gaaactgttt actggtctag 66300
gatatgccaa aatacaaaga ataagaatag aaaacccatc attattaatt atctagatcc 66360
tggaatgaaa aaaatcagta acaactttta cagatccgat gagaaagaag tctttattaa 66420
tgataacggc ataatgttta catgcatgga tcctttgggg aaatataata aggtgggatt 66480
tcttaatata tttcatgata tgtggaaata ttgtatccct tgttgttttc tacatgatca 66540
atctcatcga agtacatttt catcgtgtgt tcatcaaatc gacgttgaga aaaagatagt 66600
aagtccgtat atccttaatt ttggtaaagt tgtaacagaa tccaaaatgt catttctccc 66660
tattatcttt gacgccttct taaatgatgg aatgactgct aatatggaac aagataataa 66720
acgactaaag gaaactagtg gatatcatat agttagatgt tgtgctggtg atgatatagt 66780
tcgtttacga actacatctg atattattca gtttgtaaac gaggataaaa atattcttat 66840
agttaacgac atggtatatt ttccaatgaa cgcgtccgat ataggaaaga aaatacatat 66900
actcattcaa gaaatagttc atgaggtaat gatagtaaaa aagaaagagt ctagtgataa 66960
aatcgatttt ttcccaccca actataagtt attgaaggat ctatttccaa aacaaactat 67020
tcaaactcct attcaatctg acgcgggaat ggtgttaaca accgatggat tctacataga 67080
tggaaaactt tttaacgaag atctgtcgtc taaatacgtt acatttacaa aaaatgttat 67140
tgcgtctgat gccgtagcta aatatttttc tcctttgttt aaatacgtta tttcagaagc 67200
taaagataga tttatcaaaa cgtggatgat taatattatg atacatatga acgtagatcc 67260
taataatata ataccgacgt tagaaaaata ctatcccaac tctggaagag cacaaataaa 67320
ttaaacaact aaatctgtaa ataaataatg gacaaactta gagttctata cgatgagttc 67380
gtcaccatta gtaaagataa tcttgaacgc gagactggtc ttagcgcatc agatgttgat 67440
atggattttg atttaaacat ttttatgacg ttggttccag tcttggagaa aaaggtatgc 67500
gctattacac caactataga agatgataaa atcgtaacta tgatgaaata ttgtagttat 67560
cagagttttt cattctggtt ccttaaatct ggtgccgttg tgaaatcggt atataataaa 67620
ctagatgatg tggaaaagga aaagtttgca gccacattta gagacatgtt gcttaatgta 67680
caaactctaa tttctcttaa ctctatgtat actagattgc gtcaagatac cgaagatatt 67740
gtatccgatt ccaaaaaaat aatggagatt gtttcccatt tgagagcgtc gactacagag 67800
aacgcggcgt atcaagttct ccaacaaaac aatagtttta tcatatctac actaaataaa 67860
atcttatctg atgaaaacta tctcttgaaa attattgcag tattcgactc taaactaatt 67920
tctgaaaaag agacattgaa tgaatacaaa caattgtaca ccatttcttc tgaaagtttg 67980
gtatatggaa tcagatgcgt tagtaatctg gatatatcat ctgttcaact gagtaacaat 68040
aaatacgttc tctttgttaa gaaaatgcta cctaaaatca tactgtttca gaataacgac 68100
atcaatgcac aacaattcgc taatgttatt tctaaaattt atacgttgat ttatagacaa 68160
ttgacgtcga atgtcgatgt tggatgtcta ttgacagata cgatagaatc tgccaaaact 68220
aaaatatctg tagaaaaaat taaacagacg ggtatcaata atgttcaaag tcttatcaaa 68280
ttcatatctg ataacaagaa agaatataag acaataatct ctgaagaata tctatcgaag 68340
gaagatagaa tcattactat tttgcaagat atcgttaatg aacacgatat aaagtacgac 68400
aataaattgc tgaacatgcg agacttgatt gtgacattta gagaacgata ttcgtataaa 68460
ttctaatatc gtttttgaag tttccaaatt ttgataatat agtctagatg gaattttaga 68520
ccatctttgt caaaatcgtt taccgacaac aattctccgt tcttttcgat gactatagga 68580
caagaaccct cctctatctc ttgtataatt acatgtagca tattttgctt catcgtttcg 68640
tcagaaaatt ctgaaactag aggtaatctt cctcgttgaa gcaagttata gctttctgct 68700
attatacccg ctatttcaaa tagacttata cgtctagtat agcgtcgttt aagagcagat 68760
atatgattcc ctatatgttt aagattggaa tgcgcatctt ctatatgagt ggatgctgat 68820
tctacaatct tataagaaga tttgggatct atatcactag tttctagtga ctctccatct 68880
tcttcctctt cttcatcatc ctcgtattcg gtgagatcat cggattcata gtcgataata 68940
tcgtctgtgt ctgccattta atcttataat cgcaattcaa ttttaaagcc ttaaatggac 69000
ttctttaaca agttctcaca ggggctggca gaatcctcta caccaaagtc gtcaatctat 69060
tattctgaag aaaaggatcc ggatacgaaa aaggatgaag cgattgaaat aggactaaag 69120
tctcaagagt cgtattatca aagacagttg cgagaacaac tagctagaga taatatgatg 69180
gccgccagca gacagcctat ccaaccgcta caaccaacta ttcatataac tccacagccg 69240
gttccaacag ctacaccggc tcctacacca aaaccacgac aacaaactaa tacatcatct 69300
gatatgtcta atctttttga ttggctgtct gcagatactg atgcgccggc gagttcactc 69360
cttccagcgt tgacgccgag caatgctgtt caggatatta tctctaaatt taataaagat 69420
caaaagacga cgacgccgcc atctacccaa ccttctcaga cgttaccaac aactacatgt 69480
acacaacaat cggatggaag tatttcttgt actactccaa cggttacacc tcctcaacct 69540
cctattgtgg ccactgtatg tactcctaca cctactggtg gtacagtatg tacaacagca 69600
caacaaaatc caaatccagg agcagcatct caacaaaatc tagacgatat ggcccttaag 69660
gatctcatgt cgaatgttga aagagatatg caccaacttc aggccgaaac aaacgatctg 69720
gtgacgaacg tatatgatgc aagggagtat acgcgtaggg caatagatca aattctacaa 69780
ttagtcaaag gttttgaacg attccaaaag taataagatt gaatattaaa atcacgcttt 69840
cgagtaaaaa ctacgaatat aaataatgga agccgtggtc aatagcgatg tttttttaac 69900
atctaacgca ggactaaaat ctagttatac taatcaaact ctttctttgg tagatgaaga 69960
tcatattcac acttctgata aatctttgtc ttgtagtgta tgcaattcat tatccaaaat 70020
tgtagacgat gactttatat ccgcaggggc tagaaatcaa cgtaccaaac ctaaacgtgc 70080
aggaaataat caatctcaac agcctatcaa aaaggattgt atggtttcca tcgacgaagt 70140
agcatccacg catgattgga gtacgagatt gagaaatgat gggaatgcaa ttgctaaata 70200
tctaactact aacaagtatg acacatctaa ctttactatt caggatatgc ttaacattat 70260
gaataaacta aatattgtca gaacaaatag aaacgagcta tttcaactcc ttacccatgt 70320
aaagagcaca ttgaacaatg ctagtgtttc tgtgaaatgt actcatcctt tagtacttat 70380
tcattctcga gctagtccta gaatcggtga ccaactcaaa gagttagata aaatatactc 70440
tccatctaat catcatattc ttctgtcgac tacacgattc caatccatgc attttaccga 70500
tatgtctagt tcacaagatt tgtcttttat ttatagaaaa ccagaaacta attactatat 70560
tcatcctatt ctgatggcac tattcggtat taaacttcct gcgctcgaga acgcgtatgt 70620
acatggagac acctatagcc taatccagca actttatgaa tttagaaaag taaagtctta 70680
taattatatg ttgttggtta atcgtcttac ggaggataat ccgatagtga ttacaggtgt 70740
atcagatcta atttccacag agattcagag agcaaacatg cataccatga ttagaaaagc 70800
aattatgaac attagaatgg gaatttttta ttgtaacgat gatgatgcgg tagatcccca 70860
tctaatgaag attattcata ctggatgctc tcaagttatg acagatgaag aacagatatt 70920
ggcttctatt ttgtctatag ttggatttag acctacgttg gtttctgtgg ctagacctat 70980
aaacggcatc agttacgata tgaaacttca ggcggcacca tacatagttg ttaatcctat 71040
gaagatgatc acaacatccg acagtccgat ttctatcaat tccaaggata tttattctat 71100
ggcattcgat ggcaatagtg gaagagtggt gttcgctcct cctaacatag gatatggaag 71160
atgttctgga gttacacaca ttgatccatt gggaactaat gtgatgggta gtgctgttca 71220
ttcccctgtt atcgttaatg gagcaatgat gttttatgta gaacgacgtc agaataagaa 71280
tatgtttggt ggagaatgtt acaccggctt tagatctcta atagatgata ctccgattga 71340
cgtatcacca gaaatcatgc taaacggtat catgtatagg ttaaagtccg cagtttgtta 71400
caaactcgga gaccaattct ttgattgtgg atcgtctgat atcttcttga agggacatta 71460
tacgattcta tttacagaaa atggaccctg gatgtacgat cctctttctg ttttcaatcc 71520
gggagctaga aatgctagat tgatgcgagc tctcaaaaac cagtacaaga aattatcaat 71580
ggattcagac gatggttttt atgaatggtt gaatggcgac ggttcagtat ttgctgcctc 71640
aaaacagcaa atgttgatga atcacgttgc taactttgac gacgatcttc taactatgga 71700
agaagccatg tcgatgattt cgagacattg ttgtatctta atttatgcac aggattatga 71760
tcaatatatt agcgctagac atattacaga actattttag attatgatat ttaaatgagt 71820
tggtacgaaa aatataacat tgtactgaat ccgcctaagc ggtgttcttc tgcatgtgcg 71880
gataatttaa ctactatatt ggcggaggac ggtaaccata ttagggcgat actttattca 71940
cagcccaaaa aactaaaaat attacaggat tttctggcaa cgtctagaaa taaaatgttt 72000
ttatataaaa tattggacga cgagatacgt agagtgttaa catgaatcta cgattatgta 72060
gcggttgtag acacaacggt atagtatctg aacaaggata tgaatattgt attttttgcg 72120
agtctgtatt tcaaaaatgt acaaaggtac aaaaaaagtc aaacttccat gtgtctaata 72180
aacttattca tttgagaaat gtattgcgga gattattgtc tcatcaatgt tctggagaaa 72240
ttatctcgga actcttggat atcatggaaa aaaatcaaat atccacggat gatgtagatg 72300
caaattttgt atctagtttt cttaaggcta acgagagaat aaataaaaag gattataagt 72360
tagtctttga aataatcaat caagtaaaag atgagaaact gaatctgagt acagaaaaga 72420
ttaatgaagt agtagaaata tttaagcact tggtattctt ttgccaagaa aacactcctt 72480
ctaagacaat taattattca ttctttttgg ataaaatatt cgatatcact tctgtaacta 72540
aaaatctaaa acctcaaact gttaaaaatt atacgaaaaa taatagtaac caattagtat 72600
gggaaaactt tttagcacat atgagatcta aaaaacgtgt aactatggta gaggattatg 72660
gacacgagta tgtttttgta gatgagaggt tttctacttg ctcattagaa gtataaaaaa 72720
atagttccgt aattaaatgg ctaagcgagt aagccttcca gatgtggtta tttcagcacc 72780
taaagcagtc tttaagcccg ctaaagaaga agcactcgct tgtatactac caaagtatta 72840
taaatctatg gcagatgtgt ctattaagac aaatagtgta attgataagt gttggttttg 72900
taatcaagat ttggttttta gacctattag tattgagaca ttcaagggtg gtgaagttgg 72960
gtatttctgt tctaaaatat gtagggattc gttggcttct atggttaagt ctcacgtagc 73020
tcttagagaa gaaccaaaaa tttctttgtt gcctttagta ttctatgaag ataaggaaaa 73080
ggtcataaat acaataaacc tactaagaga taaagacggc gtttacggaa gctgttactt 73140
taaggaaaac tcacaaatta tagatatttc tctacggagt ttattgtaag ctttttccat 73200
tttaaataga aaatgaataa tactatcatt aattctttga tcggtgggga tgactctatt 73260
aaacggtcta atgtcttcgc agtcgatagt caaattccaa ctttgtatat gccgcaatat 73320
atttctctat ccggagttat gacaaacgat ggtccagaca atcaggctat cgctagcttc 73380
gaaattaggg atcagtatat tactgcgctt aatcatttgg ttctgagttt ggaacttcca 73440
gaagttaaag gtatgggaag attcggttac gtaccatatg ttggatataa atgtattaat 73500
cacgtatcta tctcttcgtg taacggtgtt atttgggaaa ttgagggcga agaattatat 73560
aataattgta tcaataatac aattgctttg aaacactctg gatattctag tgaacttaat 73620
gatatttcta ttggcctaac tcctaatgac actattaaag aaccatctac agtatacgtt 73680
tatattaaaa ctccgtttga tgtggaagat acattcagca gtcttaaact atccgattca 73740
aaaattaccg taacggtaac cttcaatcca gtatccgata tcgttattcg tgactcttcg 73800
ttcgactttg aaacgttcaa caaagaattt gtttatgttc ctgaattgag ctttattgga 73860
tatatggtta agaatgtaca aattaaacca tcgtttatag agaaacctag gagagtaata 73920
ggtcaaataa accaaccaac ggcgactgta actgaagttc atgcggcaac atcgctctct 73980
gtttatacta aaccttatta tggaaatacg gataataaat ttatttcgta tccagggtac 74040
tcacaagatg aaaaagatta tatagatgca tatgtgagta gattgttgga tgatctagtt 74100
attgttagtg atggcccacc gactggttat ccggagtctg ccgagattgt tgaggttcca 74160
gaagatggta tcgtttctat tcaagatgct gatgtgtatg taaaaattga taatgttcct 74220
gataatatga gtgtttatct tcatactaat ctgctaatgt ttggaacacg aaaaaattct 74280
tttatatata acatttctaa aaagttttcc gccattactg gaacatatag tgatgccact 74340
aagagaacaa tctttgctca catatcacat agtatcaaca tcatcgatac atctattcct 74400
gtaagtcttt ggactagtca acgtaacgtc tataacggag ataatagatc agccgaatca 74460
aaggccaagg atttgttcat taacgatccc ttcatcaagg gaatagattt taagaataag 74520
accgatatta tttctagact agaagttaga tttggaaatg atgttctata ttcagagaac 74580
ggacccatct cgagaattta taatgaacta ctgacaaaaa gcaataatgg aacaagaacc 74640
ctaactttta actttacacc aaagatattc tttaggccga caactattac ggccaatgta 74700
tctaggggga aagataaact atctgttcga gtagtttatt ccaccatgga tgtcaaccat 74760
ccaatctatt atgtacaaaa acaattggta gttgtatgta atgacctgta taaggtatct 74820
tacgatcaag gggtaagtat taccaagatt atgggagata ataactaata ataatgaaaa 74880
caaactatag agttgtaaat ggatgaaatt gtaaaaaata tccgggaggg aacgcatgtc 74940
cttcttccat tttatgaaac attgccagaa cttaacttgt ctttaggtaa aagcccatta 75000
cctagtctgg aatacggagc taattacttt cttcagattt ctagagttaa tgatctaaat 75060
agaatgccga ccgacatgtt aaaacttttt acacatgata tcatgttacc agaaagcgat 75120
ctagataaag tctatgaaat tttaaagatt aatagcgtaa agtattatgg gaggagtact 75180
aaagcggacg ccgtagttgc cgacctcagc gcacacaata aactgttcaa acgtgaacga 75240
gatgctatta aatctaataa tcatctcact gaaaacaatc tatacattag cgattataag 75300
atgttaacct tcgacgtgtt tcgaccatta tttgattttg taaacgaaaa atattgtatt 75360
attaaacttc caactttatt cggtagaggt gtaatcgata ctatgagaat atattgtagt 75420
ctctttaaaa atgttagact gctaaaatgc gtaagcgata gctggttgaa agatagcgcc 75480
attatggtgg ctagtgatgt ttgtaaaaaa aatttggatt tatttatgtc tcatgttaag 75540
tccgtcacta agtcttcttc ttggaaggat gtgaacagtg ttcaatttag tattttaaac 75600
aatccagtgg atacggaatt cattaataag ttcttagagt tttcgaatag agtatacgaa 75660
gctctctatt acgttcactc gttgctttat tctagtatga cttctgattc aaaaagtatc 75720
gaaaacaaac atcagagaag actagttaaa ctactgctgt gatttttaaa acatagttat 75780
tacttatcac tcataaatga gtaaatcaca cgcggcctat atcgattatg cattgcgcag 75840
aactactaat atgcctgttg aaatgatggg aacagacgta gtacgcctca aggattatca 75900
acattttgta gcaagagttt tcttaggatt agacagtatg cattctcttt tattgttcca 75960
tgaaacgggt gttggtaaaa caatgactac tgtatatatt ctcaaacatc ttaaggatat 76020
ttatacgaat tgggctatta tcttattggt gaaaaaggct ttgatagaag atccttggat 76080
gaacactata ctcagatacg ctccagagat aacgaaggat tgtattttta ttaattacga 76140
tgatcaaaat tttagaaata aattttttac taatatcaaa actattaatt ccaagagtag 76200
aatatgcgtc attattgatg aatgtcataa cttcatttct aaatcattaa tcaaagaaga 76260
tggtaagatc cgtcctactc gttcagtata taatttttta tctaagacca tcgcattaaa 76320
aaaccataag atgatttgtt tatcggctac acctatcgtt aatagtgtgc aagaattcac 76380
catgttggtt aacttactac gaccaggatc cttacaacac caatcgctat ttgagaataa 76440
acgtctagtt gatgagaaag aattagtctc caaactagga ggcctatgtt cgtacatagt 76500
taataacgag ttttctattt ttgatgacgt agaagggtct gcatcattcg ctaagaaaac 76560
agtattaatg cgatacgtta atatgtcgaa aaagcaagaa gaaatttatc aaaaggctaa 76620
actcgctgaa ataaaaacag gtatatcatc atttagaatt ctgagacgta tggctactac 76680
gtttacgttc gatagctttc ctgaaagaca aaatcgtgat ccgggcgaat acgcgcaaga 76740
gatagcaaca ctatataatg attttaaaaa ttcattaaga gatagagagt tttctaaatc 76800
cgcattagat acctttaaaa agggagaact attgaaaggg gatgctagtg cggctgatat 76860
ctctctattt actgaattaa aagagaaaag cgtcaaattt atagatgtat gtttgggaat 76920
attagcatcc catggtaaat gtctagtctt tgaaccattt gttaatcagt caggaataga 76980
aatcttatta ctatatttca aagtctttgg tatctctaat atagagttct catctagaac 77040
aaaagatact agaatcaagg cggtggctga gtttaaccaa gaatcaaaca ctaacggaga 77100
atgcattaaa acatgcgtat tctcttctag tggaggcgag ggtattagtt ttttctcaat 77160
taatgatatc ttcattttag atatgacatg gaacgaggcg tctcttcgtc agatagtagg 77220
aagagccatt cgtctcaata gtcacgttct tactcctcca gaacgtagat atgtaaacgt 77280
gcactttata atggctagat tatctaatgg tatgcctact gtagacgaag acctatttga 77340
aatcattcaa agcaaatcaa aagaatttgt ccaattgttt agagtgttta aacatacatc 77400
attagaatgg attcatgcta atgaaaaaga cttctcaccg atcgacaatg agtccggttg 77460
gaaaaccttg gtttcaagag ccatcgatct atcgtctaaa aaaaatatta ccaataaact 77520
aattgagggt actaatattt ggtattccaa ttctaataga ttaatgtcaa taaatagagg 77580
atttaaaggc gtagatggtc gagtatacga tgtagacggt aactatctac atgatatgcc 77640
ggacaatccc gttataaaaa tacacgatgg taaattaatt tatattttct aatcaatcat 77700
cctcagttaa tttttttaat gattcgtaat aacatcctct atggccataa catttgagtt 77760
ttgcagtatc tagagcatat tttgcaattt cgtattggag tccattacct gaattcggat 77820
ctaaaaatat tagatccttg atttcatgat tacttttaaa tgtatcaatg atttgatcac 77880
tcgttaaaga tattcttccg acaaagaaga ttacctcaaa aaatttatta ataatggtat 77940
cttctatgat gccatgaata aaaaaccgag tgtctatgaa tacaaaagaa ttgtctatat 78000
taacttcttc tttaatttcc ctggataaac actctggaac attctcaccc cttttgggta 78060
tgccacccgg ataaatagca tctattctat cattatcagt agtagctgga tctagagaaa 78120
aaaatgacga tagtatactt ctttcctgtt tggacaaata attggaataa ttcagaaata 78180
atcgtttctt tctagacatg tttctagttc taattatttc agaatagaga aaactatctc 78240
gtctgttaca tactaatatt ttgttatcag tagttaataa aatagcggac acggatactc 78300
gtttatgaca ccataggcat tggttaacga atgccgtgag tgtaataatt tgagagtcat 78360
cctcgcaaat aatagactta gctagtcgtc tattatactt aataatctga ctaattatac 78420
tagatctgta aaagttcatt tactattaac tagcatatta taaatataag acagatattc 78480
gtatttatcg tcgttaatac aatcatttaa tgatttaatc tttctaattt ctacattgta 78540
aatactagta tgcgataaat cctccaacga ttgattaata aaacacgcca tgcaataact 78600
tatatatact ttattaaata atttatcccg tgttgtaagt tttagaatta catttccaaa 78660
ttcttttact gttatacgtt catcactttc ctcttttaat tctcttctta aacaatcttt 78720
aatagattcc tttttatcta gtttaccacc caataatatt aactcttcaa agtgaggatc 78780
gatatcgttg atagaacctt ttctcaaccg tctaaagatt tctcttagtt cattgtagta 78840
cataaaccgt aatagtttag tggatactct aaagatagaa tctgaatttt gttgagataa 78900
tatcgcttgg aatgcgaatg aagttcttct agctcctatt aacggatatc cgtcacttgt 78960
tatacacgca gcaaacacat gcgtgtcttt tgatcttgga atatctttta ttcgtttaat 79020
agatattaat tctctaggag tttcaaatat cacttcctca tccattgtaa ttcccatact 79080
aagagctatt tttaaacagt tatcatttca tttttactat gccgcaacaa ctatctccta 79140
ttaatataga aactaaaaaa gcaatttcta acgcgcgatt gaagccgtta gacatacatt 79200
ataatgagtc gaaaccaacc actatccaga acactggaaa actagtaagg attaatttta 79260
aaggaggata tataagtgga gggtttctcc ccaatgaata tgtgttatca tcactacgta 79320
tatattgggg aaaggaagac gattatggat ccaatcactt gatagatgtg tacaaatact 79380
ctggagagat taatcttgtt cattggaata agaaaaaata tagttcttat gaagaggcaa 79440
aaaaacacga tgatggactt atcattattt ctatattctt acaagtatcg gatcataaaa 79500
atgtatattt tcaaaagata gttaatcaat tggattccat tagatccacc aatacgtctg 79560
caccgtttga ttcagtattt tatctagaca atttgctgcc tagtaagttg gattatttta 79620
catatctagg aacaactatc aaccactctg cagacgctgt atggataatt tttccaacgc 79680
caataaacat tcattctgat caactatcta aatttagaac actattgtcg tcgtctaatc 79740
atgatggaaa accgcattat ataacagaga actatagaaa tccgtataaa ttgaacgacg 79800
acacgcaagt atattattct ggggagatta tacgagcagc aactacctct ccagcgcgcg 79860
agaactattt tatgagatgg ttgtccgatt tgagagagac atgtttttca tattatcaaa 79920
aatatatcga agggaataaa acattcgcaa ttattgccat agtattcgtg tttatactta 79980
ccgctattct cttttttatg agtcaacgat attcgcgaga aaaacaaaac tagattcgat 80040
accttgttga gcctccatta gaacggcagt gacttcgctg ccattgtcat acgcattacc 80100
atttcgaaaa aagcagtact ttgaatcgct aaatgataca gtacccgaat ctctacttag 80160
tttacagatt aaatctccac attgaatagt tacatttgat tcatcttcga tgtttaatgt 80220
tcctctgact atatccccaa cgtgataata cgcgtaggtt attacacacg gaacgtttat 80280
aactacagaa ttattaacta tttcgccgag aggtaattcc acgtcttcac gaatttctat 80340
tttcttggcc attttaccac taatttctct atggagatac gtcttatata cggcattcct 80400
aatattagtt tttatgtcta acgtcagctc gtgtggctcc aatgtaactg gaaggtatcc 80460
attggtaaca aagctcgaca tttatttctt tatatatctc atcagtttta tggagaagat 80520
accacgttat attctttacg aaagttaact ccccaaacaa atggttcgta ggaaagtcta 80580
aacggtactg taataatatc gttttcgtat ttgtataaaa gagatttatc aaatacttta 80640
ttcgatacaa agaagtgacc gtttacaata tcatctatgt aattcctagc gtcttcttta 80700
ttttttataa ctgatgtaac cattttaagt aacttggtat cgttatactt aatacgagaa 80760
ttattataaa aaaattgtct gaccaattct cccaataaaa cttttacaat tgatggatgt 80820
ggtggaagag aatacgtttc agacatctct tgaagaatag agtatattct attcgtttct 80880
ttagtcttaa attttagata caacagcttt ttgatgtcaa atggtaaaac attaattaat 80940
tcatcctgtg tgtaatcgtt taatgacgtc acttcgtcat tgaaatcgga atatacggcg 81000
gctaaaagat atacattaac tggttcagaa atatcggcgt aagagaattt tctaatagat 81060
cgtccaagaa tttggttgta ttgagaaaaa gtatctggga tagtcataaa ccaaatatgc 81120
cttacctctt tcagagtata ggattcggac ataatgtttg acgaaaacaa aaacatcaat 81180
tgactgccat catcgttttc aggagaatta tacacatcta atagatcctc taaagacgat 81240
ttcattttac tagtaacgat agcaaatgtt tttggtttgc cgtttatcat atgtggatta 81300
gttccctgag aaccattata ttcagaatat ccattactga gcatgatata tttaattacc 81360
aatccgccat atgtagaatt agaaaagtat ataaaatgtt ttccgttgag tgtctgtatc 81420
cgattaataa agtatttaaa tttggaacta atgtttaacg ttaccaattc ttctccgtat 81480
aacacgccat tatttatttt cagatttggg tacaattcct tatcctgttc ctgaaataaa 81540
gtatctaaat tattcatcag attaagttgt cccaatactg ccattgacac gttatacata 81600
tttttatcaa acatttcatg ataacatagc tgtcgtctag taatcatata atctctctct 81660
tgaagtttag acatgtgaca atatactact ctagtatcta gaaacttacg tccgtgatat 81720
cttatcgttg gtagatcttt atcaggcatt tcgtaatatg atattcttcc tttaagcaaa 81780
tccttaagta cattcacacc tcgttcgtta agaagtgtct gaattacttt cttaccacga 81840
ctaataattt caccaaaatc tatcgtctct tcggacatta aatctataat atgacccaga 81900
gtattaggtg tgttagtaat gggagatcca gacaatagta aaaaaggaat cttgttttta 81960
ttttttatca cggtcataag ttctccagta ttattcccaa agatattatg tgcctcatca 82020
acgataaaaa tagagttatt gtagcgagat aatccgttat aattaatgac gttatcgtta 82080
taattaagag aataaaaact tgttgtggaa tgaataaaga tattctcagc tatgaattcg 82140
tcattaaaca agttcatagc tacacccata ttataattaa aaattttcaa aatgttaata 82200
ttaggcacta gaatgtaaac ctttttaaat ctggaagcta ccaaggcgaa caacaaagcg 82260
attattgttt tacctgatcc cataatatgg aacaataaca cgcttctgtt ctcatctatg 82320
atagttctaa ctagataatc tagagtagct aactgatgag gtaatatagt tggtatacta 82380
tcaacatgat tatcaaataa atctatgatt ccggtattca tttagatatg tgatatcttc 82440
tataaatata tgagcatata tttacggaga tgaaatatcc tctatgaata tatattgcag 82500
atattcatca ctaacattgg caaatttctt atgtctattg atgaagctct ctatatcgtg 82560
tccaaatagt ctagaattaa aatacttgga tattttctgt tggaaagtag tcaacggaag 82620
agtaaccaca ttatcgtaca atatatatcc ctttttggag aggtccgtca ttaatggaat 82680
atgctttaca gagctagata ctaacagagt acctattttg agatagaatg caaagtccgg 82740
aatctcttcc ggtgtaggat atagtttcat aataggaaca tgatattttt tgtaccattt 82800
caccaacaag tatagaaatg cgaatctata tctattattt tgtattttac catctaaccc 82860
ctcgtctaat agtttgactt tatcgtacgc gtcattattt tcagcagcct ctctaccaga 82920
aggttgagaa aagtgtgttc tgaatcgcac gacggcaatt cttctcatta atgcgttatc 82980
tatcctatca aagacaggtt tgtaattagt atcgataatg attgtcgcat ggtttctatt 83040
attaatttta ttggagaaac acggtcttcc aatgacacaa ggttctgtca actttttaat 83100
attgtcagat ctaattttct ttgatccact acaggcaaaa tcaggtagtt cgctacagaa 83160
tacagatctt ttcaaatgca tgttagcgat aaatggatta ggtcctttat ccaatacatc 83220
tgttaaaatt gtttgacccg tctcaacaaa caggtcaccg atagcagact ttaacaaacg 83280
tttggttgtc gactttccag ttgcagtttc tccaaaaaag aatgttaaac atcctttggt 83340
agcaccgcat aaacaactag ataaagtttt ttcgtacaac tctctatttt tcttattttc 83400
atccgttaat ggttggatat cgttaatgat attcattaac tcttccattt ctggactgtc 83460
ttcgacgaac tttgtatcgt caaatttaaa tccggttgat acagtacacg tatatttttt 83520
agcatcatct ccagagtaaa acattccgtc taccaggtcc aatacaccat ttttaaacgg 83580
aagtttatcc ggataggtat cggtctccac tgaatctatt aacatgtctc gtatgttagc 83640
ttctacagtc tttcgtttcc tcggacagag taattcgctt gaatattcct taggtagttg 83700
atgtcttatt gacagaatta gttttgttat caagggttct tcgctgttaa atttccatga 83760
attattaatc caaactatat ggtctcctcg ttcggttaat aaaacagagt tagtgtctaa 83820
aattctttgt gcaatattaa acagtttatt accatccaac ggaacaattt taactttaca 83880
actatgtgga ttaccagttt tgtaaattct aatagcacca ttttccaacg atagttgatg 83940
cggatgttta tgcgatcgtt ttttacataa tgcacaaggt gttacgtaat ctatgaccag 84000
tggtaccgtt gtaaaattat tttcatcgag atcattaaag tttattatag aattaatgaa 84060
tatttttgaa actcttttta tagcgtcttc gaatgaaata aaccctggtt cccataactt 84120
atcaggaact aaatcctcca atcgtcgttg tagagaaaag taataactat tgttgttcat 84180
atccacgtaa gtgaataggt aatcttctat attatcatgc ggtggttgca ttacatgaat 84240
agtgtcgcaa tttggatttt tcctagtacc tacaacccga agagttgttt ttctcctata 84300
tacggcagtg tctatcgatc tggttagtgg attttcagat gatctactta attctaatag 84360
tgttcgtttc atagctatca atgtatccat agtggtatac gtgtctaaaa agataatatg 84420
aaaacttgtt ttatctctat ttgtagactt agtcaatgaa aaattagatc tcatggattt 84480
tattacattt tcatgaatgg caccgcattc tgtaaacgcg aatctagcta cacagtttga 84540
cacctcgata ataaaatctt gaatagccgt taaataatct atttcgtcta gacacgcgtc 84600
taaatctaca tccatgaaaa ttctgactat agagtatgct tcctcatccc taagactttc 84660
gaatagtgta cattctggat tattctcaat atatctttct aactcgtcgc atttaaatgc 84720
ttctacaaat cttggatctt cattttgtct gcacgctgac gggacaccta tagtcttaag 84780
aacaaagata acatcattac ctctaatagt tgcatccatt tagaacacaa gttaaaattt 84840
cactaaagca ttaataaata aacccttgag cccaatttat aggtgccttg ttgtctaatt 84900
ccagtaaaac gttgataatt tcaaatgatc tatctttctc gaattggcgg tctctagccg 84960
ctggatgata tccgactatg gtagttaccg gggattctaa ctttgcccgt atattcgaga 85020
aatctgtttt acccaaacaa taaagaacac taacgtgttt agttatatgc tgcagcagta 85080
acttggaaat cttatcccag tagatcgcgt gactttttgt ttctcctaat ttacaactta 85140
agtaataatt ccagggtata accccgtcta ttatattaag gttataacct ttataatcaa 85200
ttactccggt taatctagat atagatgaag ctatctcctt aattgatttt tttgtaaaat 85260
ttggtgattc gaacggtaca ccagttccat ctttcggata cggatctata ccacacacac 85320
atactcgttt atttctaagc ggttgtttca actgtataaa gaacttatca ggaataggcg 85380
acgtctcgtc tcgtagcagc caactggcta cttcgttata aaactctacc aattgactca 85440
ttactggttc ccaatcatcg tgataagtaa tagtatatgg cgcgtgtgat acagtcactg 85500
aattcattat atcaaattag ataccttttt atacgtatct agtacctttt cattttccga 85560
aacgccgtta aaccaagcga atacaaacgc cttaaactta tctctattat aacatattct 85620
cgttagattt aattcttcgg tatccttgta tctaactatt gttatatgtt tagaaactct 85680
atagtggctt ctaatcagat gttctaataa atattttaaa aatgaatctt gattaaaaat 85740
catatcattg accatttgtc tggctactga attacgataa tacggagaca ataacggatt 85800
agtcaaatag ctatcatctc ctaatgatgg aggcacctgt acaaatacca atcgtttatt 85860
cttgaacgaa tcaaacgtat aaatatcata aatgacaaat ttatcagtgt gcatatcttc 85920
agatatatga ttggatgtag aacaccatct aacttgtctt ccagcatcta taaattcctc 85980
cacctctata tatctaccac cgtgctgaaa actagaccca tttaattcga cgcataaaga 86040
tccatatgta tctggagtca caatatattc agaaaaaaat acatgctcct ttaattttgt 86100
taattttgat ctgataaagt cattgtgatt tcctaaaagt ataaatactt cgttatcgtc 86160
gttatcgact ttgggatact tattatcctt aactataaaa atgtccatca atatcgatat 86220
aaaaaaaata actgatttac tcaacagtag tattttattc ccagatgatg tgcaagaact 86280
tcttcgagag aaatatatag tattagaaag aaaatcaaat ggtacaccta cagtagctca 86340
catctataag acaatggcta gatttgataa taagagtata tatagaatcg ccaagttttt 86400
atttatgaac aggccagatg ttatcaaact tttattttta gaagacgtag aacctctgtt 86460
acccgacaaa agtattaata tatctattaa caatacagag tatccacagt tggaaggtcc 86520
tataggaaca aaaatcgctc tattggaatt atttaatgca tttagaacgg ggatatcaga 86580
acccatacca tattattatt taccgcttag aaaagacata aacaacatag taactaagta 86640
agtcttcgac atctaaacct tcacatttaa tggctcctct atttagttcg aaaaagtttt 86700
ttgtagacgg tctatcttcc attgtagatg cgccattaat aaacttttta cttcgttcta 86760
taattgtagc gaaatcaacg ttatctacaa gaacaaatcc gtattcgtta aacactctga 86820
ctatatcgtt ctttttgata atgtattcag tcattggagt agacattgtt gatggattat 86880
ataccactat tctatcatca gctatttttt ctacagacat atagttttcg ctactaggta 86940
aattcttatg aattataaaa gtctttttat ctgttaattt tgataatttg tctccgtcca 87000
tggtagtgat taataccttg cctccagaag cagttagttc ggataagtta ttcatgacgg 87060
tagcataatg tctcggatga aaagaataat ggatagcaaa ctgccagtcg atgatattaa 87120
actttccaaa atagaatact tctctgacac tagagacaaa tgtatcggat cgaatagttt 87180
cctgaatgta gtcaaatttg tagtacttgg ttttaattcc agagtttaat ttgttgtatc 87240
tttcatttcc tctagctata gcatcagcat ccggatccgt cgctaccaat aacgcaatct 87300
ctccataaaa gtatttttcc aggtccgcac cgtttccaaa atcaatcgcc aatacctttc 87360
gtttgttgga atcgtctaaa aatgttttgg aacaatacat agaaataaga agagtcttga 87420
cgtagtttga taaaattccc aacggtcctc tagttcgttt attcgtaaaa taactaactt 87480
ctggatttaa tctaaattta tcattattgg cgtattgatg tcccacatcc gatagtttat 87540
cctcgttaaa gatatctcct attttgatgc tttgatctct taaatgttcg actatgatat 87600
tatgttgatt tccataataa tcttctgagt taatatattt catggtttta tcaattctag 87660
gtttaagtat ttctccatta actaagaatt ctgctataaa cttaataggt acaaccacgg 87720
acttaatacc cacttcatta tgtgtattaa tatattccaa acaatagata ttatttagat 87780
aattaacgcc gttatataac acaatcttac cagaaccata ttctttagga aagcctttat 87840
cgttgctaaa tttcttatac tctacaaaga tagacgattc tccaaagata attggttcac 87900
tggacatgta cctaaatact acatttgcag tttggtctat agtattttcc tttttaattt 87960
taaaatcaat gttagattta ggtccctttg aatagaacag aataacacct tctggttgct 88020
ttggtaaata tgtagataac atatcgacga cttcactagt tgtagtaaac ggaccttcgt 88080
atttctttga cttgaatact atccgatcac aaatatccac tagtttagat tcaacatact 88140
tactttcttc tagtctatca ttgattgcat tcacaggctc tattagctta atgagatata 88200
cggtccagtt cttatcctta actgcctcac caaagactac tacttcggaa tctattattc 88260
tcttaacagg atatctaata atataaccaa gatgtgtaaa ataacaatac aacccttttg 88320
atgtaactct gatagttata ggaattccgt cagtcttagt tacggcatat agattttcca 88380
gatccaaacc tactatatct tgtttaggca acataaaggt ttttataggc gcgttaatag 88440
gcggagaaag aattacattc tctggagaag ccataaatat atgacgtgat agagtcgtca 88500
attcctttat tagttcatca tatggaactt tttcattgtc tctaggtgtg aattctattt 88560
ccagagatgt attaggcctt gactttggat gattaatagc gtgtaataaa gaacttttag 88620
actgggcacc ggatcctaga aaatatttta gcttaaagtc tatcgtaaag ttttttgttt 88680
ttgcttgaat aagattgact aattctagtc ggatagagga tccatatttc ttgtaatcca 88740
aaaatatatg acgttcctct gtcgatagtc tcaacaagca ttctttgtga agacgatttt 88800
ccgtcactaa tgatttcttt tcccaaacta tgttatctat agcatctact aactgtacat 88860
tttttacatc tagaccatgt accttagata atggaatctt agttctaatt ttaacacctt 88920
ccttattagt aacggtaaat cgaataaacg attcctgaat cgtagagata ttcactacat 88980
ttgtcaaagt aattaatggc ggcttaataa atactagttc caattcatta tttatttcgt 89040
atgcggtaga cctctgttct aattctgaag cattcttcgc taaagcgtct atatacgttg 89100
caatagtaga agatgatact atgttggcat ccatattgtg ttttattata aacgactagt 89160
tttttttcat ttacttatta acaagcgtct tttatatatt cgtaatctat gcctttagct 89220
agagctattt taagcttttc tgtatctcga ctgatacgag tatctgatct attgcggtat 89280
ttttttataa atcgtttaag acggggagta gttttgatat attcgctaat atcctcttta 89340
ataatatcca cacacgccaa ttgttcggct atactcgatg cgtgagtctt gcattcatct 89400
ccagatatcg gagtgagggt cagatccaaa tattgagaag ccttataatt atcgtattcg 89460
aaatcaatca taaactgacc atccttatcc actgaaaaaa tggtattgtt tggatggcgt 89520
ttaaatatag acattatcaa tgccataata tctaatgtgt ttagctctcc gaagaaagct 89580
gtcattgcga gagatttcat acgcttatcc atttccattt atcggtcttg taattatttg 89640
tgtaaagatc tatatcatcc atccgtagat gatttaacgt gatctacgac tatagatagg 89700
aattcatcga acgtagtttt agatactaca tctaaaaaat ttttatcctt taccatttct 89760
aaaatagtcg ttgccatata agctcttttt gaaattgatg gagtatgacc taccacttca 89820
gcagtttgtt tgatagttaa cgctattaac ttttttggtg acggaagagg agatatggac 89880
tttacatttg tccaaaaatt atataaaaac gtataattga ctccatacgt tcggagatcc 89940
ttgattctaa taccaaactg tttgatacat tcgtatacct ttcgttcact tagtttgttg 90000
aacagaaatt cttcgggact agaatcatcc gtcagtttca atagcggttt atatagtcta 90060
ttagacttat gaacaacaaa ttcatgtgaa actttgtcct ttcctacaaa cttgataact 90120
atttcatcgg gacttatttc tatgtgttta ttttttagtg ttaataaccc tactgtttca 90180
ttctccttaa gatatttcat tttaccaaat ctaataaaaa acatagtttc cattaacata 90240
aaaaccgcca actgataatt ggaatctgtg gacgatttct ttatattttt gtttataaaa 90300
caattaattc gtttcataac gttatatact ctaacaaaaa tacgatctct tttagcgttg 90360
cgattctgta catgcatttt tccgtaaaag tattgtctac gtccttttga atcacttccc 90420
acaaaaatta atctagttaa cgcctcctcc cacgtttgtt catatactac tacatctgtt 90480
aaatgagtag gaattttaac atgttgcaaa acctcatacg ctggattatc gtctgataca 90540
ggatttaaaa aattattatc ggtaaagagt ttaccatctt tataaaaaag tgcacgcatt 90600
tacttcttac aagttttaac ttttttacga acaactttag attttccctc ggtgactaga 90660
tcagatagtg ttgtaatagc tttagtcata gaagtaaatt gtctagagat accagctgct 90720
tgaacatcct ctagaaccgt cgatactgca gagattctag taataatttt cttaagatct 90780
ttaacgatat tgtcggtagc cacctttagg tcagaaagat cgcttctagc actatgattt 90840
actttaccag cttcaacttg taccataggt tcatcatccc cgtcgctatc atcgagctct 90900
acagcagcca cgctttctac aatgtcgctg actccaggag atggagaatt tttttcagtt 90960
gtttgatgat attcctctat aactacttct tcttccactt cctccttttt ggttgatctt 91020
ttagtagccg ctggtttacg aggagtagtg gctcgtttgg ttttgggctt agtagatgga 91080
attattacat cttccgggaa aatatcctcg tttttatctt tattttcagc gctatttttt 91140
agatgagctc tgatttcagc catctttgtg aagctactag tatccgcttt atttgtaatt 91200
gaccacgcca ttacgataca aacttaacgg atatcgcgat aatgaaataa tttatgatta 91260
tttctcgctt tcaatttaac acaaccctca agaacctttg tatttatttt cattttttaa 91320
gtatagaata aagaatctat aaaaactaaa aaaattatac atcataaacc aatttcctag 91380
ttgtttgtaa ctttaaatgg actctaaaga gactattcta attgagatca ttccaaaaat 91440
aaaagcatat ctactagacg cgaatataag tccaaaatcc tacgatgact ttatctcacg 91500
aaataaaaat attttcgtta tcaaccttta taacgtatcg actatcacag aagaagatat 91560
acgattgtta tacactacga tagaacagaa tattgacgcg gatgatcaaa cactggttgc 91620
tattttttcg tatataggat ataaatttga acaggctgtt aaagaagaga ttagtacgag 91680
tttatccttc aatgacaaga ataccacaga tgaaatgacg tataacttgt atgatctttt 91740
ttttaacaca ttagacatgt atttacgaca aaagaagatc agtattctgg taaatgatga 91800
tgttagaggt gatgtaatcg ttagttataa aaatagtgac ttagtttcat catttaatgc 91860
ggaactagaa ccagagatta agaagatacc gttcaatatg aaaaatctat taccgtactt 91920
ggaaaagaat ttggaccaac taagattctc taaaaaatat ttagactttg catatttatg 91980
tagacacatc ggtattccca tttccaaaaa aaagtataat gtgcgatatg tatttcttta 92040
taaaatagac ggattatcca ttcctattat cattaaggat tttttagatg ttaagtacgt 92100
atatttggaa aatactggaa aaatttataa aaattctttt tccgaagacc ataacaacag 92160
tctatctgat tggggtaaag tcatcatacc tctcttaaag gatcgtcatc tatatagcta 92220
catctttcta tctagttatc atttacatag ttactataca gatctcatcg cgagagacga 92280
gcctgtgttt gtgaaacgca aaaaactaga tattatagag atcgatgaac ctgaggcatg 92340
gaaaagggat gttagagtgg aattcgcacc gtgtgagcat caaattagat tgaaggaagc 92400
tatgaaagtt gacgctaact atttcactaa aattaataat tttgctaacg aatttattta 92460
ttatgaagat ggtgtggcat attgtagagt gtgtggaata aatataccta tatttaattt 92520
agatgccgct gacgtgatta aaaatacagt tatcgtttcc acgtttaaca agactatatt 92580
cttgagcgaa ccatatagct atttcgttca tagtcagcgc tttatcttta atattatcat 92640
gtcttttgat aatattatga aatctcaaac ttgggtaatg aaatacaaca ttaaccgact 92700
aattcttaac tttcttattg atataaactc tagacgtcag gaatacgaaa aaaagttttc 92760
ttctgaaatt aagagaggtc tgttctttct tcgtttgtct gcaaacttat tcgaaagtca 92820
agtatcgtct acagagttat tttatgtttc caagatgctt aatttaaact atatagttgc 92880
gttagtaatc attcttaaca gtagtgcgga ctttatagtt tcttatatga aatccaagaa 92940
caaaacggta gaagaatcca ctcttaaata cgccatctcc gtggttatat acgatttttt 93000
ggttaagact agaatttgcg agaagggatc gttggatact atagttttat ttaccgatgt 93060
atacacatct ataatgccgg aggaattgga tttacatttt cagagaatca cattagaact 93120
tagaaaacta gtatccattc agagatcggc gttagaaccc aattacgatg tagaaagtcg 93180
cggcgaagag cttccattat ctgcattaaa gtttttcgat acaagcacca ttatagttaa 93240
gacaatggct ccagtacata catacatcga acaaaaaatt gttgcaccta ctccatcggt 93300
cgaaccaact gatgcatctc ttaaaaactt caaagaacta acgtgtgacg aagatattaa 93360
gatctcgatt agagttcatg atactaatgc tacaaaatta gtcatttttc catcacatct 93420
aaaaatagaa atcgagagaa aaaaactaat tataccgcta aagagtttat atattaccaa 93480
tactctcaaa tattattatt ctaactccta tttatacgtt ttcagattcg gagatcctat 93540
gccattcgaa gaagaactca tagatcacga acatgtgcaa tacaaaataa attgttacaa 93600
tattctaaga tatcatttat tgccagacag tgacgtgttt gtatatttta gtaattcatt 93660
aaacagagaa gcattggaat acgcatttta tatctttttg tcgaaatatg taaatgtgaa 93720
acaatggata gacgaaaata taactcgtat taaagagttg tatatgatta atttcaataa 93780
ctaaatggcg gcggtgaaaa ctcctgttat tgttgtgcca gttattgata gacctccatc 93840
agaaacattt cctaatgttc atgagcatat taatgatcag aagttcgatg atgtaaagga 93900
caatgaagtt atgccagaaa aaagaaatgt tgtggtagtc aaggatgatc cagatcatta 93960
caaggattat gcgtttatac agtggactgg aggaaacatt agaaatgatg acaagtatac 94020
tcacttcttt tcagggtttt gtaacactat gtgtacagag gaaacgaaaa gaaatatcgc 94080
tagacattta gccctatggg attctaattt ttttaccgag ttagaaaata aaaaggtaga 94140
atatgtagtt attgtagaaa acgataacgt tattgaggat attacgtttc ttcgtcccgt 94200
cttgaaggca atgcatgaca aaaaaataga tatcctacag atgagagaaa ttattacagg 94260
caataaagtt aaaaccgagc ttgtaatgga caaaaatcat gccatattca catatacagg 94320
agggtatgat gttagcttat cagcctatat tattagagtt actacggcgc tgaacatcgt 94380
agatgaaatt ataaagtctg gaggtctatc atcgggattt tattttgaaa tagccagaat 94440
cgaaaacgaa atgaagatca ataggcagat actggataac gccgccaaat atgtagaaca 94500
cgatcctcga cttgttgcag aataccgttt cgaaaacatg aaaccgaatt tttggtctag 94560
aataggaacg gcagctgcta aacgttatcc aggagttatg tacgcgttta ctactccact 94620
gatttcattt tttggattgt ttgatattaa tgttataggt ttgattgtaa ttttgtttat 94680
tatgtttatg ctcatcttta acgttaaatc taagctgtta tggttcctta caggaacatt 94740
cgttaccgca tttatctaac actattccat attactaaaa tcggaacacc aatgcggtga 94800
cataaaataa ccgctataac ctaattcatt taacatctca ttaccacaag taataacatt 94860
attagacttg tgttttatca aatactgaca aaattgttga gcagatggat cgacctttgc 94920
cgccttttta accatccacg cgtctccagt acctcgccta atagcttgcg gcagatatgt 94980
tttcttatcc aatcgcatag ctataaaata ggcgccgaaa tccacacatt tgaattcgaa 95040
tatatcatcc ttaccagcgg ctagaagtct acctctatca ctttctaatt ttgttttgct 95100
atccgttaat gatttccaat cgttaaccgt atttttaatt cgcatatatc tcgttaattc 95160
attaaagact ggattatcag acgtctgaaa ccagagtaat agcgcactaa ttgccaatat 95220
aataacaaag aatataagtg ttgatgtttt ggctgcttgt acgcctacta tagccttttc 95280
tctaacgtat tctaaattac acgcgtttac cgataaagta gttttatcca tttgtacgtt 95340
ataaatggat aagaaaagtt tgtataaata cttactacta cgttcaactg gagatatgca 95400
caaagccaaa tctcccacta taatgacaag agtaaccaat aatgtgtatt tgggaaatta 95460
taaaaatgct atggatgcac catcatctga agttaagttc aaatatgttt taaatttgac 95520
gatggataaa tatacattac ctaactctaa tattaatatt attcatatac cgttggtaga 95580
tgatacaact accgatatta gtaaatattt tgacgacgta accgcctttt tatctaaatg 95640
tgatcaacga aacgagcccg tgttggttca ttgtgctgcg ggagtaaata gaagcggggc 95700
tatgattttg gcatatctaa tgtctaaaaa taaggagtca ttgcctatgc tatatttttt 95760
atacgtgtat cattctatga gggacttgag aggcgcattt gtggaaaatc catcgtttaa 95820
aagacagatc atagaaaaat atgttattga taagaattaa aagtcttctg tttcttccat 95880
ttccttgatc ttttgagaag atatcttatc agatagtttc ctttccattc tcatgagaag 95940
acccaagtcg ataaagtatt tgtaatatcc agttcctata ttagggacct tgctaaaaaa 96000
gtggcagcta ctattatcgt taataggttc tgacttttta tgaagagccg cgtttaacaa 96060
tgctttattg tctccgaacg tagctctctt aagagtacta gctgcgccga acttgaattt 96120
attcactgat tctggttcgt aactagcaca tagtaaacta gcgagaagat cacaaggctg 96180
atacagataa tcgaaccctt ctccataggt gtttaacatg gcttcgcaca agtattcacg 96240
agcggcctcg ataccgaaga tatcgtatgt attccatact ccaggataca cgttgacgtt 96300
ttccaaatcg aaagaaccca attcttttag attcatgagt tctacagtca tcttattgag 96360
cttttttgtt tgattgaagt cgtcatatcc cgtataatca gagataggaa tcttgaattt 96420
actaatcttg cccttgttgg cggcacccgg aagaaccatc ataaacttac taagattcaa 96480
ttcttccggt tcaacgaaat ttaggtagac agtaaatcta atattatcct catcctcaat 96540
gaatgtttcc ataccccatt cctttacaat gacgctaaag gagatgaatc gttcaatcat 96600
atattcgacg actaattcgg taatttctgc tctcttgatg tataatctat tgactattat 96660
atctactaca tacctatctg tttcttttcg aagagtgatg tttggattta attctcccaa 96720
acatacaaat tcgaaattaa tcttaacaga ttgaagttta gagatatcat cggataccag 96780
agtgataatt tcggtcttat tcttactcaa attagtcaag ttattaaact cgttgaaacc 96840
aagtttttgt ttgacggcac cacttttttc agtagtgtga aaactggaca gggcttgttg 96900
tgtaaacttc tcagacaata cctgtgcaga aataattcca ataggagttc caccacctag 96960
agtataattg agtttttcat agaacttttc aaagatagtg atagccgttt cttttgtaat 97020
tctaattcta gaaggattaa gatgcgtcaa gaatatatac tccataaaat ctatattaga 97080
taccgtaaag aagtatttct ctctcacatc atcaatgacg ttatgaatca tatcgtacag 97140
atccttaacc ttaatagcat tatcctcagt ggtgggtttg acgaatacta ggaaattaaa 97200
cggcgccaat gtcttttttg caagtttctg tttctgagag taaacgaatc cctgttttat 97260
tttattccac agagcactaa tttccaaata ccaagtcatg gactcatctg gatagataag 97320
atctacaggt ttacatactg agcctagaat tttggtataa ttggcggcgt acttgatgag 97380
cgtattacct ataactactt gtccgtatcc gtcgaccacc atatcctcca tctttttaat 97440
gatttttcta gccagtgttc cggtacgtga tgtttcacag acgatatcag tagattgaga 97500
tcttgcaacc agcatcgaaa agtaatattg agaacccgtt aatccttttg ttaaagaatt 97560
aagaatgtaa cctcttcctt ctggatcctt agagtctgga agatagtaag gtaagactct 97620
acccaatact cgagtctctg ctggttcacc atcaatcctc tgttgtccat aagtacctag 97680
aatatacatt agttctgtgg gatttacttt ataacccgct ttggccattt tcaggaggtt 97740
attatctgga tcatctatca gcgtttgtct catatgttct tctatctctc ggatattaag 97800
atttgtcaag ttggataaca tggattccac atagtccgcc tctaaagctt tagataatgg 97860
aactattttc ccgtctctta catcgttgag atatttggcg tatgcttctt tgataagttc 97920
tattttttct acgttgatgg cctccaattt attagtgaac gtcgaatttg gtctcagatc 97980
tttgaatgtc accccaaaac cgtaaataga tagatatctc ttaaaaacat aagatgactt 98040
gataataaag ttgatacctt ccacgttcga cttatgatcg gataagagtc cagccaatga 98100
cagatgcctc atagccacaa caaaattact atctacgtcg tttgcaataa tttcaccatc 98160
ctttaagaga cccggataat taatcttttc acctatcaag taagtataga tatctttacc 98220
gctgaattta catttacctt taggatcgaa ctctcttcca tatttcccca agatgttcaa 98280
tacttcatct aaacaaagat cttgtatcct aaacaatgaa tacgctgcta cgatttcatc 98340
ttgaatagat ccataaacgg gggctccatg aatatcgtgt ttgagtaacg tcgtcggata 98400
cataagaata ctttgttcaa ttacggcttt aggattttgc tccaatatca tccattcttc 98460
atctccgtcg aaatcagcat tttgagagtt gacaattccg ggagatattt tgatagtatc 98520
tccttcggta gctctgatag atgaagcgat gacgttgtat ctatgtagag acggctgtct 98580
tccaaaaata atacttgtat attcttgaac agctacttct acccaatcac caggcaataa 98640
atgtatttta tttttgataa actttccttg gcgtattctt gttaattggt ttaatcgttt 98700
attaaagtaa aatttaactt ggtttgacgc taatagttgt ttaactttat ccactgtaaa 98760
ggcattaaca aatatctttt ctgtaagtgt atttctaata tatgcgggca ttcctacctc 98820
attaacggtg atagatgtac tgggaccaat tacagatcta gcggtctgat cttttcgccg 98880
ggcgacgata taacttctaa tcatattatt tttgccggat gtgatatatg ataaattgat 98940
actggaagtg ttattagaaa taattttaat atcatcgtat tctattaccg ccttctggat 99000
aacctgttca tcagcattca agttacaatt cttaacgatc atacctaata agtaagttaa 99060
ttcattggtt tctttgggta tactatctat ccaaaaacta atagccggtc taataatcaa 99120
cggagggatg ggaaagtagt ctgtataaaa taagttagct ggatattgat gaatttctaa 99180
taatggccaa aacttttcat gaatagaaat taacttttga tagatgagag aattaggaac 99240
gttaatatca tccaacttgt tgacgaaaca aacctttttc tttgaaaaag taattttttg 99300
atacggttgc atacattcac tgttccaaca tgactttttc ttggataata ttttatcctt 99360
taatctccta agagcgtgtc ccgataactc ttttaggtta atatcgtcgg aatacggttc 99420
tcgtgaacgc aataatccgc agtgaataca tatataattc agtaaacgaa taatttctga 99480
aataaattca ggcttaacta tatgagtttt ataaatactt actttacccc agtgaccgaa 99540
acattccaat tccgttttcc cacaagtttt acataatgcc ccatccatag cacctagtct 99600
accatcttta acggtaccga tatcgtcgtc atttttaaca tgactaatga taatatctgt 99660
agcattaatc tctttttgat catatagact atacgtaacc ttagagatta cagccatttt 99720
tatcaagtca gtttctttta aagaaccgaa agtatacaat caaatttccc tttttattac 99780
aactataaaa taatagttat atttacactt taaattttta tcatgacgga cgaacaaatt 99840
tatgcattct gtgatgctaa caaagacgat atacgatgta aatgtattta tcctgataaa 99900
agcatagtac ggataggaat agatacaaga ttaccctatt attgttggta cgagccatgt 99960
aaacgaagcg atgcgttgtt accagcctct ttaaaaaaaa atataacaaa atgcaatgta 100020
tcggattgta ccatttcatt gggaaacgtt tccattacag atagtaaatt agatgtaaat 100080
aatgtttgtg attccaaacg agtagctacc gagaatatag ctgtccgcta tctgaatcag 100140
gaaattagat accctattat agatatcaaa tggcttccga ttggattact agcgttagct 100200
attttaatat tagcattttt ctaaacaaga tataagatat aaaatatatt attgattatt 100260
ataatgttct tatctcatct ctactaattg attaatcagc gactgaaata acagatctat 100320
cggctatctc tactccagtt accatgttat tgcggaaaaa tctaacaatt tttaatggta 100380
tattaggacg gtagagaatc ttgacaacta tttccgtctc taacattttg ggaagacgaa 100440
gagtcttttt accatcgcct gtttgtagta cactattaac tatattagtt tctgtagtat 100500
ctagtctaac aaagctagga aataagtcag atattaccac atctatgtat agaaaattta 100560
caggaaactt gttatgacct ttttgaagat acgatgttat aatgattggt tctccataat 100620
catcatcaac cggagtataa tttatggatg attcgttaaa tacctgaaac acagttttca 100680
tagaatcaat tttatgtcta acggttatta aagtaactaa atcattatac tctatatcgg 100740
tagtatatct cagtagtacg tttctattta ttactgcgta cggatctctt gctatttctg 100800
tttttagaca tagaattttt gctagatatt ttacgttgta ttggttcatg actaactttt 100860
tcagttgatg ttgttggaat atttaagaaa cgaaatatag attgttgtag aaatagtacc 100920
tttgctttag tagtaggaaa tgttttattg cagtacacgg tcctcagcat aaagtacatg 100980
tgaaaatagt catattcctg attaggataa tcaaagttaa caactacttt gttacggacg 101040
atcttattaa ggtagtacat ctttttttca taatttacag cgtctgattt ggtaactcga 101100
gtcagtctca tgttctcacc ggtataaata cttaataatc tcatttcagc tgaatatgaa 101160
ggagcaaaag gttgtaacat tttattaccg tgtgggatat aaaagtcctt gatccattga 101220
tctggaaacg ggcatctcca tttaagacta gacgccacgg ggtttaaaat actaatcatg 101280
acattttgta gagcgtaatt acttagtaaa tccgccgtac taggttcatt tcctcctcgt 101340
ttggatctca catcagaaat taaaataatc ttagaaggat gcagttgttt tttgatggat 101400
cgtagatatt cctcatcaac gaaccgagtc actagagtca catcacgcaa tccatttaaa 101460
ataggatcat gatggcggcc gtcaattagc atccatttga tgatcactcc taaattatag 101520
aaatgatctc tcaaataacg tatatgtgta ccgggagcag atcctatata cactacggtg 101580
gcaccatcta atataccgtg tcgctgtaac ttactaagaa aaaataattc tcctagtaat 101640
agttttaact gtccttgata cggcagtttt tttgcgacct catttgcact ttctggttcg 101700
taatctaact cattatcaat ttcctcaaaa tacataaacg gtttatctaa cgacacaaca 101760
tccattttta agtattatat taaaatttaa tcaatgttta tttttagttt tttagataaa 101820
aaatataata ttatgagccg acgtaacact ttctacacac cgattgatac atatcattac 101880
ctcctattat ctctatctcg gtttcctcac ccaatcgttt agaaaaggaa gcctccttaa 101940
agcatttcat acacacagca gttagtttta ccaccatttc agataatgga ataagattca 102000
aaatattatt aaacggttta cgttgaaatg tcccatcgag tgcggctact ataactattt 102060
ttccttcgtt tgccatacgc tcacagaatt caacaatgtc tggaaagaac tgtccttcat 102120
cgatacctat cacggagaaa tctgtaattg attccaagac atcacatagt ttagttgctt 102180
ccaatgcttc aaaattattc ttatcatgcg tccatagtcc cgttccgtat ctattatcgt 102240
tagaatattt tatagtcacg catttatatt gagctatttg ataacgtcta actcgtctaa 102300
ttaattctgt acttttacct gaaaacatgg ggccgattat caactgaata tgtccgccgt 102360
tcatgatgac aataaagaat taattattgt tcactttatt cgactttaat atatccatca 102420
cgttagaaaa tgcgatatcg cgacgaggat ctatgtatct aataggatct attgcggtgg 102480
tagctagaga ggattctttt ttgaatcgca tcaaactaat cacaaagtcg aacaaatatc 102540
ctttattaag tttgaccctt ccatctgtaa caatagggac cttgttaaac agttttttaa 102600
aatcttgaaa gtctgtgaat tttgtcaatt gtctgtattc ctctgaaaga gattcataac 102660
aatgacccac ggcttctaat ttattttttg attggatcaa taataataac agaaagtcta 102720
gatattgagt gatttgcaat atatcagata atgaagattc atcatcttga ctagccaaat 102780
acttaaaaaa tgaatcatca tctgcgaaga acatcgttaa gagatactgg ttgtgatcca 102840
tttattgatc gcaaaagctt tgcacaatct ttatacacta tcggtttact atttattgat 102900
aacgcagatg tttgagttgt catccatggt aatccataga tcattaattt atcgtcttca 102960
cacgctagat tagcacgtcg taatctatca ataggatcgg gtatttttcg tttaggcatg 103020
aagaacatat ttaattcaga tctaaaaaat acatatatta gaatgaatac aatgaatact 103080
tcaaataaaa ctattaatct gtgtttataa acacttaata aagaatgttt aaacgtgggc 103140
tctataaaca caggattaaa gtatacatta ggaacattct ccatttatag taatcaatcc 103200
tttgtcggaa tatctgttag aggaatattc tttttaacac attccaatag tcccagaaaa 103260
tcatttaacc taatgggttc ttgaagaggg ctagaactat acgattctag ttccttatta 103320
gtactaagtt tctctagttt atttttattg gtgaatccgt aaatggcatt caatctcatg 103380
gatgtggaag gagaatacac attcaggaca ttaattcccg catatttaga tatcaaagcc 103440
ttgttgtctc cgataggtgt atactcagtc gacgcggatt ccatattttc tttataaata 103500
ttaatctttt tacgagtttc gaaaatacac aagataggtg atgatccttg acggaaaata 103560
accatgttct tattctttct cctaccactt tttttaggaa tgacggcagt catatccgta 103620
ttattaatga taagaggcat aacctcattg ttaggatcca agaaatagtt ttcaatggct 103680
tcaatagtta gtttatcatc tcctagaccc aaattgtttc ttatattata cattgtggta 103740
aacattgccc ctgtgatatt ctcgttatga atcaactcca actcatattt tgacatcgtt 103800
ctaggtacta tattaaaaat agaaagcata gatcttggaa atttggattt tgcgccggca 103860
ataaccattt gtaaatcatc atactcagat atacttcctg caaaaaatat ggtatcttct 103920
tcgatgaggt tttctagcag tagactcatt tagagaagtt ttttttgtga taaatgaata 103980
cccgtaccga tgttacaaac gataatatag acaaaaatcc aaccaaacga ggtgatagaa 104040
atataccagg aagaaatgaa agatttaatg accaaaatag attcaacaac gatataccaa 104100
agcctaaacc aagactacag cctaatcagc caccgaaaca agataataaa tgcagagaag 104160
agaatggaga ttttatcaat attagattgt gtgcctacga aaaggaatat tgcaatgacg 104220
gatatctatc tcctgcctat tatatgttaa aacaggtgga tgatgaagaa ataagttgct 104280
ggtcagaact atcgtcgttg gtgagatcca gaaaggcggt gggatttcct ctattaaagg 104340
cggctaaacg tatttctcat ggatcgatgc tatattttga acagtttaaa aacagtaaag 104400
ttgtgaaatt aaccccgcaa gttaaatgtt taaatgatac tgttattttt caaactgtag 104460
ttattttata ttccatgtat aaacgtggca tatattctaa cgaattttgt tttgatctgg 104520
tttctattcc cagaacgaac attgtttttt ctgttaatca attaatgttt aacatttgta 104580
cagacatatt ggtagttcta tctatttgcg gcaaccggct ctatagaaca aatctaccac 104640
agtcgtgtta cttaaatttc atacacggcc atgagacaat agcccgtaga ggatatgaac 104700
actccaatta cttttttgag tggttgataa aaaatcacat atcgctattg accaagcaaa 104760
cgatggatat tctcaaggta aagaaaaagt atgctacagg agcaccagta aataggttgt 104820
tagaacctgg tacactggta tatgtgccca aagaagatta ttactttata ggcatatcac 104880
tcaccgatgt gtcaattagc gataatgtca gagtattatt ttccacagat ggaatagtgt 104940
tagaaataga agactttaat atcaagcatt tatttatggc aggtgagatg tttgttagaa 105000
gtcagtctag tactattata gtataaagta ataaaaaata gttaatgtga tgactagcgc 105060
caccaacgcc aacaacattt gataatttct acttactaga cgtaccgtaa aaatataaat 105120
tactataaca aataatagta tatcaataaa caacctaatt aatggtcgaa gtatagcagg 105180
acattgatgc tctagaccgt gtataacaaa atctacaaat ttttcatccg ctatattttg 105240
tttcactata tcgtctagac gatcagcgat aacttccatg ttaatctatt aaaatattat 105300
caatatattt tcagttttgc atatccgtgg tagcaataac catcggagaa gttctaaaga 105360
atgtgtccat gtaagtagtc caatggacgt tttccttatt ggctaaaata agtttgattt 105420
tatcattggt ggatgtgaac aacatacgct tggcatagta cataaacaac gctgccaata 105480
ttataacacc gataacaatc atataaaact gaactcctgt accagcaact tgtctaggtg 105540
ctatttgagt agtggcctta gtcgtcaatt gcatcaacgc tttaatggca caatttcctt 105600
tgctagatcc tgtattaata aattccaaat ttgttggaga tcctggggct ccgtaacatt 105660
catctatgat tacgttttgt atctttaatt tgttatcgac gaccgcgcta gaattacaag 105720
tctgtttcac ataattttca aaatctctaa caacagtgtt tacactcgtc tgaatgttta 105780
acgcagcagt aaacatagct ggtacgtatg ctttttgttc cggtgttaat ccactatatg 105840
tttctgtagc ggctgataac acagcatcca actgagcatc cgcgtccgca gagcacatat 105900
ttttaacagt gaggttacat ccatggtttt gtcggatata aaaatttccg atttctatat 105960
cacattttgt ttgagcacta gcgttcgctt cttgttctaa tttagacgag atacgttcgc 106020
tgagtgtatt caccgtcgtc tgtatgcttg ccgcggcacc catttaaata gctacaatta 106080
gtatccatat taccaagaga gataataaac tgatcaaatg caattttagg tcgaacgaat 106140
gtttaatatt atgttgaact acttttgctc tattgacggg aacagtagaa aatctatcac 106200
tattgcttaa tccacatgac aatcttaatg aggaagtttt atccatctgt aagttgttca 106260
cgctagtatt acatcgtaca atattgcaaa gtcctaaatt attataatta cgtgttagta 106320
agaaattaac attggcattc gaacactctg gatcccaaca ttctcgaggt tccgcatatt 106380
ttaatgactc ttctaactta tctctagtgg gataactaca tctcatatat ttctgtttaa 106440
agtccgcaga ctgttgtctt agaatataat cgatcatctc tttgctatct tctgtattgt 106500
gtgcgcgtaa atgatgcaaa aatgattcac atattggtac actagcatct ttactacata 106560
atgtttgcat cttattatac agatttatta acgattgttg accctctaca gttctatcac 106620
tcctattaaa ggctgaaccg atccactgat ggcatatgtt tctatcgaac gtatccccct 106680
gacaccagtc gaataaatca acatcgcatt ttccagtgtc gtgaacgtct ggccaacacg 106740
attctaatac tgcaccctct tcatacttat ctgatatctt tccatccttt ttccaataat 106800
gagtacgatt aaaagtgcga cagcaattgg gtgcggttcc attatacgat tgtcttaaca 106860
atgccgaaag accaccgggt cctgtgttga ctaatctaaa ctctggatat cttttcttta 106920
ctttatcctc tttatctttt gctagtggtc ctatatgcac atattctaaa agcttagcgg 106980
gagctatcac gtcatgcatt ttatccacgt ttaataacat ctcatcagtg ggtactcccg 107040
gaggcggatc ccgtttaggg agctcaacac ttactctgcc acccatattt atctcattga 107100
aagtattaat ctaaaaacgt cataaagatg ttgatcttaa aggattgaac tctatccgaa 107160
aacaacattc ctagaatgtt atcgtcatta tccattacga ttctagtttc aaaaacattg 107220
actctctttt tgaatcctcg tagtttgttg agagacgaga tagctatttt gaaagaaaac 107280
ttttgtagtt cttgagaaca ttcagtcata gaatattccc tggaaaacgc atcagtatta 107340
ccaggagtct tcataataat attgtcatct ttaaacataa tagccaaatg ctgatgctga 107400
ctaatacact tgataaagcc caacaaccat tctaaatgaa tgacggttct accacaacat 107460
ttttcttcat acttgtgaaa attaaacacg taagatttct tttgatctat acttagacaa 107520
atagtagtat ctgtcctaat aggcatcagt tccttgttac aatcgacact tactacatga 107580
taactagaaa gttttactag attattttcc agatcaggtt ctatatctat gatggcatca 107640
ttgtgaaaac tacacaaaca cgattttacc ttggacacag gaagattaaa cacaatgttt 107700
tcggctccgc ggtagaacac tgatgcactg agaggtataa tggcccaaat gtttacagat 107760
ccgcccaagg cggcaaaaat atacattaac tcatccgtcg agtctacatt tatagatact 107820
tcttcactga actctgaaaa atatgccaca atttggcgca gtttatcgat ttttatacgg 107880
atgctcattt taaatttttg taaattattt aaagttaaat ggctgcagaa cagcgtcgtt 107940
ctacaatttt tgacatagtt tcaaaatgta tagtgcaatc tgtattgaga gatatatcta 108000
ttaattctga atacatagag tccaaagcta aacaattgtg ctattgtccg gcatcgaaaa 108060
aggaatcagt gattaatggt atctacaatt gttgcgagtc aaatatagaa ataatggaca 108120
aagagcagct attaaaaata ttggacaatc ttcgatgtca ttcggctcat gtatgtaacg 108180
ccacagattt ctggagacta tataattcgt taaaacggtt tactcatact accgcattct 108240
ttaatacatg caagcccact attctagcca cgctaaacac tttgataacc ctgattttat 108300
ctaacaagtt attgtatgcg gcagaaatgg tagagtatct agagaaccaa ctagattcat 108360
caaataaatc aatgtctcaa gaactagcag aattattgga aatgaaatat gctctcatta 108420
atctggtaca atataggatt ttgccaatga tcatcggtga gcctattata gtagctggat 108480
tttctggtaa agaaccaatt tctgattatt ctgcagaagt ggaaaggcta atggaactac 108540
cagttaaaac tgatatagtg aataccacat atgacttctt agccagaaaa ggtattgata 108600
ctagcaacaa tatagcagaa tatatagccg gcttgaaaat agaagagatt gaaaaggtag 108660
aaaaatattt accagaagtt atatctacaa ttgccaatag taatataata aaaaataaaa 108720
aatctatctt tccggccaat atcaacgata aacagatcat ggaatgctct agaatgttag 108780
acacgagtga gaaatactct aaaggatata aaactgatgg agctgtgact agtccattga 108840
cgggaaataa tacaattaca acatttatac caatttctgc gtccgatatg caaaagttta 108900
ccattttaga atatctttac attatgagag tgatggcaaa caacgttaag aaaaagaacg 108960
agggaaaaaa caacggagga gtagttatgc atattaactc accctttaag gtaatcaatt 109020
tgccaaaatg ttaaattatt agaatcatat atctttatcc atctattatc atctgtgaag 109080
ttttggctca gaaaaatatc tttacctaat attcgtttag acgatgtatc aataccggca 109140
tttttataac attcagctac caatttaaaa caatacattc tattatgacc aaatccatac 109200
ggaataccca ataaagttaa tgacgtatca gctgctattt tcataacttg aatattctct 109260
aacatgtata cttttgcact aagatatcct tcaaaaaaac tatccaatgg gactattcga 109320
actccttttc tataggtaga ttcaactacc aagtgttccg ataataacgt accataataa 109380
atacccacat gtttttctat cgatggattc aaatgacttg ttaatgacat ggtataatta 109440
ataaaaataa tagaacctct aggcgcatat gtcttgataa aattaaccgg atccatatta 109500
gtttatatcc aatagaggtt gcactgttaa gttacgttga ggttctattt gtgtagataa 109560
ttttaaccta caacattcgt tctttacact gacgagtaca tcctttaatg atttttttcg 109620
tataatcaat ttatatcgtt cgtgagaaat atctttgccg cacgtagagc acacgagttg 109680
gaacaccatt tttaatctag taacctatat ttattatatt atcactttta gtattggtta 109740
ttaacagact atcgttaaag taaaatgaac tatttatact cagtagtaaa ttatccttat 109800
agatgccgaa cactatagtg ttacagtttt cgttagaata tccgaagatc gaagatatag 109860
attttataac atcgatatct gatttagtat tttcgaaatc tatataagat gataaagttt 109920
taacttctga aacatcaatc tccttgcgtg gttctaatgc atacattaat tggcagggta 109980
acggaacggt ctctaaataa gatgatttaa aattgttcca tttttcatct aatgcggaaa 110040
atataaattc ttgaacagtg cattgacaag gaggaacata cgagtagaca tcgtctaaat 110100
tagcgtaatc gtttataaac gtaacaatat tacgcacgtc tacggtagag ttagtctttc 110160
tataataatt tttaattgcc aaactagtga ctatattatc gattgtaaaa tcactaaaca 110220
attgtatttt gtttaagttg gtgggtgtta tagatgcccc atagagtcca ggaaagaaat 110280
cacatccatt cactaacgcc gttaattttg ctaaatagtt atcctctgcc gagggaacaa 110340
atttaaacag ttgagttaag ttttttatca tcttaggatg attatcagta gatgcaaata 110400
gcatagtatc ctgatcggta cttattatca acggccattc tcctgtggta gagaaatgtg 110460
ttttagcctc gagacacata acgaattctg cgtctcgttc atcacaataa aataatgtaa 110520
cattctcatt attgttgaaa tgtgttagta tctcattcaa tgatattttt atgttatcag 110580
aatcagataa atatatttga aatgtgagtt tatcgatttt taattgcatt tctgccttta 110640
tttcttcttc cataaatccg gtaacatttt gtatttcgga tgtacacttt tctaattcta 110700
gcatttttct gtccttggtt aatttagaat atttacgtct cttgtctcta acgtcttgtt 110760
taatttttat acttcctcta tcgataaaaa gggttacatg ccctcccttt tttacccatc 110820
cgtttacgta ttttatgaat accgtagtta actcttctaa gtttctgaca caattggcga 110880
cggctatata aatactcatt gtatccacaa atattccatt gtatactttg tataaattat 110940
catctaatat cgtcagtgat ttattttcca gcagtaacga ttttaagttt ttgataccca 111000
taaatgaaga acgtactgat tattttcggt aaaccgtatt gtagtatttg tgaaaatgtc 111060
agtgatgcag tagaagaatt aaaatccgag tatgatatac tccatgttga tatcttatca 111120
ttttttttaa aggatggtga ttcaagtatg ctgggtgacg taaagcgcgg aaccctaata 111180
ggaaactttg cagcgcatct atctaactac atcgtttcca ttttcaaata caatccacag 111240
acaaaacaaa tggcatttgt ggacattaat aaatccttgg atttcaccaa aaccgataaa 111300
tcgctggtga atttggaaat tctaaaatcc gaaatagaaa aagcaaatta tggagtttgg 111360
ccaccggtta ccgaataaaa tatcttcctg agtattttgt ttattgttcc gcttccttta 111420
tcaaataaat tttgaagtat ttgataattt attggatcga ctagttcatc tatacatttt 111480
ttggaaacga gaacatctac ctttttattt gttgttatat gcgacgttgt atacgccata 111540
aatgtaactt gagaaaatcc acaaagaatt aattttgaac cagttatggg gacgcgctca 111600
ttagaatatg tataaatctg aggagtgtat tccttgagga gatattctat caagtcatca 111660
tttgcttctc taatataaat attcctgtcc tttataacaa ctatgccttt tagattatct 111720
cctaatttat aacacggccg tatacacttg gaatacttgt acaatctaag atagactaaa 111780
tctctcagag ttgtatcatg gaattccata cttaattcct ccgataaatc tacatgttca 111840
aatactttag aaatatattt atggtatttc ctatctggaa agtaagttat caagtcatca 111900
taagatattt caaatcctct acataaggaa gacactatct ccaacgattc ctcatcttct 111960
gtaagtagga atttggacaa gttaaacaaa attagatctc taaatggcat ctttattata 112020
tcttatttta tttttgttat tcgtatgtat ttcttattat tttacatatt atccgaccaa 112080
taaacttcag gcagctgtaa tggaaacaga tagagaaaac gctattatta gacagcgaaa 112140
tgatgaaata ccgactagaa cattagatac agctatattt accgatgcat caaccgtcgc 112200
gagtgcgcaa atacacctat attataattc caatattggt aaaattataa tgtcacttaa 112260
tggtaaaaaa cacaccttta atttatacga tgataacgac atacgaacat tacttcctat 112320
tttactcctt agtaaatgat tgtcttaccg aataaagttc gtattttcat caacgatcgg 112380
atgaaaaagg atatctactt gggaatttct aatttcggat tcgagaatga tatagatgaa 112440
atcttgggaa ttgctcactt gttggaacat ctacttatat cctttgattc tactaatttt 112500
ttagcgaatg cttctacatc tagaagttat atgagttttt ggtgtaaatc cattaattca 112560
gcaacggaat cggacgcaat cagaacatta gtttcgtggt tcttttctaa cggaaaactc 112620
aaagataatt tttccctttc tagtatacga tttcacatta aagaattaga aaacgaatac 112680
tattttagaa atgaagtatt ccattgtatg gatatactaa cgtttcttag cggaggcgat 112740
ttatataacg gtgggagaat agacatgata gataatctta atatagttcg tgatatgctg 112800
gtaaatagaa tgcaaaggat atcgggatcg aatatcgtaa tttttgttaa gagattagga 112860
cctggaacat tggatttctt caaacagaca tttgggtctt taccagcatg tccggagatt 112920
attccttcgt ctattccagt aagtacaaac ggtaaaatag ttatgactcc gtctccattt 112980
tatacagtta tggtaaagat taatccaaca ttagataata ttttagggat tctgtatttg 113040
tacgaaactt accacttaat agactatgag actatcggca accagttata tttaacggta 113100
tcctttatcg atgaaactga atacgagagc tttcttcgtg gcgaggctat attacaaatt 113160
agtcaatgtc aacgtattaa tatgaattat agcgacgatt atatgatgaa catctattta 113220
aattttcctt ggctatcgca tgatttatat gattacatta cacgtattaa tgacgatagc 113280
aagtcgatac taatatcctt gacaaatgaa atatatgcat ctataattaa tagagatatc 113340
atagttattt acccaaactt tagtaaggcc atgtgtaaca ctagagatac ccaacaacat 113400
ccgatagtag ttcttgacgc aaccaatgat ggactgatta agaaacctta tagaagtata 113460
cccctaatga agcgtctaac atctaatgaa atatttatac gatacggaga cgcgtctctc 113520
atggacatga taactttatc attgtctaaa caagatatat cattaaaaag aaatgccgaa 113580
ggaatacgtg taaaacatag tttttcagct gatgatatac aggcaattat ggaatctgat 113640
tcgtttttaa agtatagtag atcaaaacca gctgcgatgt atcaatatat atttctatca 113700
ttttttgcta gtggtaattc catagatgac atattggcaa atagagattc taccttagaa 113760
ttttctaaaa gaactaaaag taaaattttg tttggtagga ataccagata cgacgtcact 113820
gcaaaatcta gttttgtatg tggtatagta cgaggtaaat cattggataa aacgtctctg 113880
gttgaaatga tgtgggatct caagaagaaa ggattaatat attctatgga atttaccaat 113940
ctattgagca agaatacctt ttatctgttc acatttacta tctacactga tgaagtatac 114000
gattatctaa acactaataa acttttttct gcaaaatgtt tagtcgtgtc tacaaaagga 114060
gatgtggaaa atttttcatc tctaaaaaaa gatgtggtca ttagagtttg atttttagtt 114120
attatctaca ggaacaaata tagtatctga aatcatattc atatatcccg ttagaggtct 114180
atgataatat atagtagcgt ttgttccgtt atagacaccg aataatattt tacaaaagtg 114240
tatatacgta tcatcatctt tatgtttaaa atttaaaatc ttaattcgta aatttagaga 114300
taaaatggct tcttgtacaa tactagttaa ttctcccgtc ctctcaaaat tatccaactc 114360
ctcagcgaga ataggactta gtacataaag tttagcatac tctatcatct tcatataata 114420
attggataat aatttattcc atgtttctgt actaatatcg aacgagtcta tatattcctt 114480
tgtacgccat agaatatcca aatttgtagg gattataaac aaatcttcgg ggagtgttag 114540
attaaactta ttagcgtaca atatataatt atgtagaaat tctgaatcta ttcgctgtat 114600
agacttcata taagacagat catagaaata tacgtatgtc ccaggattaa ctcttcctac 114660
tcttcctttt cgttgatctc tcatagattt agaaataaat tcttgcgatc ctccaaaagg 114720
agcggggaca aaaactctac ccatatcata aatgtgtgta acattgcgta tagtaacgct 114780
ggattccaaa taaggagtag aaataattat cgatacatta ggtgatgaat acactttttc 114840
taatatttcg tctatatcta agaccttacc atgaataata tacatatcat acggtaatct 114900
tttttctaaa tatgatttat attcgtgaca ctgtgcaacg gatgccacaa agactatacc 114960
ggatgatcca tcaggaggag tatacatctg tatagcagta actaaatttc tcttttcttc 115020
ttctatgtat gccattctgg aagatggatt tatcttatta tgaataaata cctcgctaat 115080
tttaaacagt gtatctccag gaatatgtat aaatgcggga ttaggtaaaa atacttttag 115140
ccgttccctg tcatcctcta acgtggcagt cattaaaaac atagaatcta ttttcgtatg 115200
atgctttctc gctactgcta taataatatc tcctatttga tcatgctcat gaacttcgtc 115260
tataataaga gtgccataac taaatagttt tgttagagat aacttatggg tagaaaatac 115320
aattccatat ttttttggtt gtttgtttat taattcttcc ggtatagatc cgtaccgtaa 115380
agaaatagga gatccatcta gtaccttaaa tcccaatgat tttaaaatgg tattgctatg 115440
caatctaact aaagctatcc taggaagaga tagaatgact ggtctttcgt gaaagtcagt 115500
gattttatct agagtagaga atccaccaaa taaataatta aaccaaagca ataacttggg 115560
tacctgtgac gtcttaccca ctccagttcc tccagttaaa actacaggtc tatgagaaat 115620
ccacgctgaa aatatctctc gttgtgcttt aggagttaat gaggccaatg gaattttgct 115680
aaatggatac ttattcccta gtacacctat agtatctgtt cgtttaccta cggaattgga 115740
aaatatctgt aaactattac cagcttctaa tagtcctctt aatatatact catcgaacga 115800
attgatttct gtatttgtta tacattttag aaaactataa cattcaaagc ttattgtgtg 115860
ttcactgtat atatattgct tcgcggttag gtttatgtgt gcgggttttc ctagtgatgg 115920
aggagatact ttttttccac gtgcttctgt actaactttg tatattcctt tatgttttac 115980
aacgtgtgcg ttatgccatc tatgttttat aactggaaac accgccaatg agaaactatc 116040
acgttccgtt ttactcatat tactgaattc atcttgtgaa tatttgtaag agaatacatt 116100
aacgcagttt ggaaaaaaga agatatctgg taaattcttt tccatgataa atggaaagat 116160
atacagattt agtaattagt aaaataccag aactaggatt taccaattta ttatgtcata 116220
tatattcact agctggatta tgtagcaata tagatgtatc taaattttta acaaattgta 116280
acggatatgt agtggagaaa tatgataaat ctacaaccgc cggcaaagtg tcttgtattc 116340
ctatcggtat gatgttggaa ctagtagagt cggggcacct gagcagaccc aatagtagcg 116400
acgaactcga tcaaaagaaa gagttaaccg acgagttaaa gacgcgttac cattctatat 116460
atgatgtctt tgagttacct actagtatac cgttagcgta tttctttaaa cctcgactac 116520
gggaaaaagt atctaaggcg atagacttct cacaaatgga tttgaaaatc gatgatttat 116580
cacgtaaagg aatacatact ggtgaaaatc caaaggtcgt caagatgaaa atagagcctg 116640
agagaggagc ctggatgagc aatcgaagta ttaagaactt agtctctcag tttgcttatg 116700
gatccgaagt ggattatata ggacaatttg acatgagatt cttaaactcc ttagcgattc 116760
atgaaaaatt tgacgcgttt atgaataaac atatcttatc gtatatactt aaagacaaaa 116820
ttaaaagttc tacctctaga tttgtaatgt ttggattttg ttatttgtct cattggaaat 116880
gtgtaattta tgataaaaaa caatgtttag tatcctttta tgactccgga ggcaatattc 116940
caactgaatt ccaccactat aataattttt atttttattc cttctccgat ggttttaaca 117000
cgaatcacaa acattctgta ttggataata caaattgtga catcgatgtt ttattcagat 117060
ttttcgaatg tacatttgga gcgaaaatag gctgtattaa tgtagaagtt aatcagctgt 117120
tggaatctga atgtggaatg tttattagtt tgtttatgat attgtgtact aggacaccac 117180
ctaagagttt caaatctctg aaaaaggttt atacattctt taaattttta gcggataaga 117240
aaatgacatt atttaagagc attctattta acttgcaaga tctatccctg gatataacgg 117300
aaacggataa cgcaggatta aaagaatata aacgtatgga aaaatggacc aaaaagtcaa 117360
ttaatgtgat atgtgataaa ttaactacaa aattaaatag aatagtaaac gacgatgaat 117420
aactttgtta aacaagtagc ttcaaagtct ctaaaaccta ccaaaaaatt gtctccgtca 117480
gatgaggtga tatctttaaa cgaatgcata atatccttta acttggataa cttttattat 117540
tgcaacgatg gactgtttac taagcccatt aatactccgg aggatgttct taaatcactc 117600
ttgatcatgg aatcattcgc ctacgagaag atgataatca aaggattgat aaaaatacta 117660
atatctagag catatattaa tgatatttat tttactccat tcggttggtt gacgggcgtc 117720
gacgatgatc ctgaaacaca cgtggtgata aaaataattt tcaattcatc actaatatct 117780
atcaagtctc aagttataga atatttaaaa ccatacaatg tcaataacct atcggtactt 117840
accacagaaa aagaattaag tattaatacg ttcaatgttc cagattctat acctatgtcg 117900
ataatttcgt ttttcccatt cgatacagat tttatactag ttattttgtt ttttggagta 117960
tataatgact cgtattgtgg aataagctat ataagtccga aagagagact accgtatatc 118020
atcgaaatat taaaaccgtt ggtgtcggaa attaacatgt tatcggatga aataggtaga 118080
acatcatcca ttagaatctt caattccact agcgtcaaaa aatttcctac taatacatta 118140
acatccattt gtgaaattgt ttattcgttt gatgaatcat cctttccgac gcctaagacg 118200
ttcactcctc taaacgcgag tccatacatt cctaaaaaga tagtttcact attggattta 118260
ccatctaatg tggaaataaa agcgatatct agaggcggtg tggatttcat cactcatatt 118320
aataataagc gtctaaacac aatcttggta atagcaaaag ataacttttt aaaaaattct 118380
acattttctg gaacttttat caaagagaat attatttgga agggtatcta tacttataga 118440
ataatcaagt ctagttttcc agttcctact attaagtcgg ttactaataa aaaaaaaata 118500
tgtaagaaac attgtttcgt caattctcag tatacaacta ggactttgtc acatattctt 118560
tgatctaatt tttagatata aatggtggat gctataaccg ttctaactgc gatcggcata 118620
actgtattaa tgcttttgat ggtaatttct ggcgccgcca tgatagtcaa ggagttaaat 118680
cctaatgata tattcactat gcaatcatta aagtttaatc gagccgtaac gattttcaaa 118740
tatataggac tctttatcta tataccagga acgataattt tgtacgctac atacgtcaaa 118800
tccctattaa tgaaaagtta aataattttt tttattacac caacaaaaat gtttgtcatt 118860
aaacgaaatg gatacaagga aaatgtcatg tttgataaaa tcacgtctcg tattagaaaa 118920
ttatgttatg gcttaaacac ggatcatata gatcctatta aaatagctat gaaggttatt 118980
caaggaatat ataatggagt aacaacggta gaattggaca ctctggcagc cgaaatagca 119040
gccacttgta ctacacaaca tccggattat gccattctag ccgccagaat agccgtatca 119100
aatctacaca aggaaacaaa aaaactattt agtgaagtga tggaggattt attcaactat 119160
gttaatccta aaaatgggaa acattctccg attatttcaa gtatcaccat ggatatagtt 119220
aacaaatata aggataaact caactcggtt attatttacg aacgagactt ttcatacaac 119280
tattttggtt ttaaaacttt ggaaaaatcc tacttgttga aaataaacaa caagatcgtt 119340
gaaagacctc agcacatgtt aatgcgtgtc gcagtaggaa ttcatcaatg ggatatagac 119400
tcagctattg agacgtacaa tctactttct gaaaaatggt ttacgcacgc ttctcctacc 119460
ttatttaatg cgggaactag tcgtcaccaa atgtctagct gttttctact taacatgatc 119520
gatgatagca tagagggtat ctatgacacg ttaaaacgat gcgcattaat ctctaaaatg 119580
gcagggggaa taggtctatc aattagtaat attcgtgcca gtggaagcta tatctccggt 119640
accaatggta tatcaaacgg tattattcca atgttgagag tttataataa caccgctaga 119700
tacatagatc agggaggaaa caaacggcct ggagttatgg ccatatactt ggaaccgtgg 119760
cattctgata ttatggcgtt cctcgatctt aaaaagaata caggaaacga ggaacataga 119820
accagagatc tatttatagc tctttggatt cctgatctct ttatgaaacg agtgaaggat 119880
gacggagagt ggtcgttgat gtgtccggat gaatgtcctg gattggacaa tgtttgggga 119940
gacgagttcg aacgattgta tacactatac gaaagagaaa ggagatacaa atctataata 120000
aaggctcgag tcgtctggaa agcgattata gaatctcaga ttgaaactgg tactccattc 120060
attctttata aggatgcgtg taacaaaaag agtaatcaac aaaatttagg aactatcaag 120120
tgtagtaatc tttgcactga gataatacaa tatgcggatg ctaatgaggt agccgtttgt 120180
aatctggcat ctgttgcctt gaacatgttt gtaatagatg ggcgatttga ttttctcaaa 120240
ctgaaggatg tggtcaaagt aattgtcaga aatctcaata aaattataga tattaattat 120300
tatcctattc cagaagctga aatctctaat aagagacata gacctatcgg tattggtgtt 120360
caaggattag cggacgcgtt tattctctta aattatccat ttgatagcct ggaagcacaa 120420
gatctaaata agaagatctt cgaaaccatt tattacggtg cattagaggc gagttgtgaa 120480
ctagctgaga aggaaggacc atacgataca tatgtaggat cgtacgccag taacggtatt 120540
ctacaatatg atctttggaa tgttgtaccg tcggatcttt ggaattggga acctctaaaa 120600
gataaaatca gaacatacgg tcttagaaat agtttattgg tggcacctat gccgactgca 120660
tcaactgctc aaattttggg aaataatgag tcggtggaac cgtataccag taatatttac 120720
actcggagag tattgtctgg agaatttcaa gtagttaatc cgcatctcct tagagtttta 120780
accgagagaa aattatggaa tgatgagatc aagaatagga ttatggcaga tggtggatcc 120840
attcagaata caaaccttcc agaagatatt aagcgagttt ataaaactat ttgggaaatt 120900
ccacaaaaga cgatcataaa aatggctgca gacaggggag ccttcatcga tcaaagtcaa 120960
tctatgaata tccatatagc agatccgagt tattccaaac taacgagtat gcatttttac 121020
ggatggagtc tcggtctaaa aacgggaatg tactatctac gtacgaaacc cgcatccgct 121080
cccattcaat tcacattgga caaggataaa ataaaaccac tggtggtttg cgattccgaa 121140
atctgtacat catgcagtgg ttaaacaaaa acatttttat tctcaaatga gataaagtga 121200
aaatatatat cattatatta caaagtacaa ttatttaggt ttaatcatga gtaaggtaat 121260
caagaagaga gttgaaactt caccaagacc tactgcatct agcgattctc tacagacttg 121320
tgcgggtgtt atagagtatg caaaatcgat tagtaaatct aatgcaaaat gtatcgaata 121380
cgttacacta aatgcttctc aatacgctaa ttgttcgtct atctctataa aacttactga 121440
tagtttatct agtcaaatga cttccacttt tattatgttg gaaggagaga ctaaacttta 121500
taaaaataaa tctaaacaag atagaagcga tggatacttt ctaaaaataa aagttaccgc 121560
ggctagtcct atgttgtatc aacttctaga agccgtctat ggaaacatta agcacaagga 121620
acgcattcca aattctttgc atagtctttc ggtggaaact attacagaga aaacatttaa 121680
ggatgaatcc atcttcatca acaaattaaa cggatccatg gtagaatatg tttcgactgg 121740
agaatcatcc attctcagat ctatagaagg tgaactagaa tcactcagta aaagagaaag 121800
acaattggcc aaggcaatta tcacacctat cgtcttctat agatccggaa cggaaacaaa 121860
aattacattc gcactcaaga aactaatcat tgatagagaa gtggtggcta acgttatcgg 121920
actctctgga gatagtgaac gtgtatcaat gactgaaaat gtagaagaag atctggctcg 121980
taatctggga cttgttgata ttgatgatga atatgatgaa gatagcgata aagaaaagcc 122040
aatattcaat gtataaatgg ataagttgta cgccgctata tttggtgtat ttatggggtc 122100
tccggaagat gatttgacag actttataga aattgttaaa tctgttctaa gtgatgagaa 122160
aacagtcaca tcaactaata ataccggttg ttggggttgg tattggttaa ttattatttt 122220
ttttatagtt cttattctac tactattgat atatttgtat ttaaaagttg tttggtgaac 122280
ttaaatggcg gaatttgaag atcaactcgt tttcaatagt atcagtgccc gtgcattgaa 122340
agcttatttc actgctaaaa tcaatgaaat ggtagatgag ttggtcacaa gaaaatgtcc 122400
acaaaagaaa aaatcacaag ctaagaaacc tgaattacgc attcctgtag atcttgtaaa 122460
gtctagtttt gttaaaaagt ttggattgtg caattatgga ggaatcctta tcagtcttat 122520
taatagtcta gtagaaaata atttctttac aaaggatgga aaactggatg atacaggcaa 122580
aaaggaattg gttttgacag atgtcgaaaa acgaattctt aataccatag ataaatcatc 122640
tcctttgtat atcgatatta gtgatgttaa agtattggct gctagactaa aaagaagcgc 122700
tacacaattt aactttaatg gacatacata tcatctggaa aatgataaaa tagaagatct 122760
cattaatcag ttggttaagg acgaatccat tcaactggat gaaaagagtt ctattaaaga 122820
tagtatgtat gtcattcccg atgaacttat cgatgttctc aaaactagat tgtttagatc 122880
tcctcaagtc aaggataata ttatttcgcg tactagattg tatgattatt ttactagagt 122940
tactaagaga gacgaatcgt caatctatgt gattctaaag gatcctagga tcgctagcat 123000
tttgtcacta gaaactgtta aaatgggcgc ctttatgtat acaaaacata gtatgttgac 123060
gaacgctatt tcatctagag tcgatagata ttctaaaaag tttcaagaat ctttttacga 123120
agatattgta gaatttgtta aagaaaatga gagagttaat gtatcgagag tggttgaatg 123180
tttgactgtg cctaatatta ctatatcaag taatgctgaa taaaaatatt tataaatatg 123240
ctcgtcgtaa ttatgttttt tatagcgttt gccttctgta gttggctatc atatagctat 123300
ctgcgtccat atatctcgac taaagagtta aataagtcga gatagtttta tatcacttaa 123360
atattaaaat ggccgaggaa tttgtacaac aaaggttggc caataacaaa gtgacaattt 123420
ttgtcaagta tacatgtcct ttttgtagaa atgcactgga tattctaaat aagtttagtt 123480
tcaaaagagg agcgtatgaa attgtcgata ttaaagaatt taaacccgaa aatgaattgc 123540
gtgactattt tgaacaaatt actggtggta gaactgttcc tagaatcttt tttggaaaaa 123600
cttctattgg tggatatagc gacctgttgg aaatagacaa catggacgca ttgggtgata 123660
ttctatcatc tattggggta ttgagaactt gttgagaaaa taatgaaaaa acaatactta 123720
atcatgtcgc cgacatgttc atgtatccgg aatttgcgag gaaggcttta tcaaagctta 123780
tttcaaaaaa attaaacatt gaaaaggtgt ctagcaagca ccagctcgtg ttactggatt 123840
atggattaca cggactattg ccaaaatcac tgtatctgga agctattaat tccgatattc 123900
tcaatgttag attctttcct cctgaaataa taaacgtcac tgatatcgtt aaggctctcc 123960
aaaattcttg tagagtagat gagtacctaa aatctgtttc cttatatcat aagaattctt 124020
taatggtatc gggaccaaat gtagtcaagc ttatgataga atataatctt cttacacaca 124080
gtgacttgga atggttaatt aatgagaatg tagtcaaggc tacatacctt ttaaaaatca 124140
atgcctatat gattaacttt aaaatagatc taacggttga tgaaatcatt gacttagtta 124200
aagatattcc tgtaggagct acgctacatc tatataatat attaaacaat atagatttgg 124260
acattgttct tcgtatatct gatgaatata atataccacc tgttcacgat attctgtcta 124320
aacttaccga tgaagagatg tgtataaaac tagttacaaa gtatcctatg gacaatgtta 124380
taaattttat taatcaagat gttagatata gtcccacctt catcaagaca attaaagatt 124440
ttgtcaacaa gcatcttcca accatgtacg atggattaaa tgattatcta cattctgtta 124500
ttatcgacga ggacttaata gaggaatata aaattaaatc cgttgccatg tttaatttgg 124560
aatacaaaac tgatgtagat actctaacat tggacgaaca gatatttgta gaggtaaaca 124620
tctcatatta tgattttaga tatagacaat ttgccgatga atttagagat tacattatga 124680
taaaagaaag aagacaaatc accatgcaat ctggtgatag aataagaagg tttagacgtc 124740
ccatgtcatt gagatccact atcatcaaaa aggatactga ttctctagag gatattctcg 124800
cacatataga taatgccaga aaaaatagca aggtatccat tgaagatgtt gagagaatca 124860
tttcatcttt ccgtcttaat ccttgtgttg tcagacgcac catgctgtct gatatagata 124920
tcaaaacaaa gattggaaat cttgtgctct gacactatca gccatcaaag gaattatggt 124980
aacagatacc atcaataccg tgttatccaa aattctgcat catcatagga atgtcttcaa 125040
gtatcttaca tctgtagaga ataaagaaat tgctgtctgt cgctcttcta tagagaatta 125100
aaaagtgtac gatgtgatct acgcacagat gatggattat tggataggct atacgatctg 125160
actagatacg ccttacacgg aaaaatcaat caaaacttaa tcggtcaacg atgttggggt 125220
ccgttgacag aaatgctgtt taacgagaat aaaaagaaaa aactaaataa tttaatggaa 125280
tacatcaaaa tatcagacat gttggtatac ggacactcta tcgagaagac gcttattcca 125340
attactgatt ctctttcatt caagctatct gttgatacca tgtctgtgtt aaatgatcaa 125400
tatgccaaga ttgtcatctt cttcaatacc atcatagaat atattatagc tactatctat 125460
tatagattga cagtcttgga caattatact aatgtcaaac attttgtatc caaagtgtta 125520
cacactgtca tggaagcatg tggcgtactg ttttcataca ttaaagttaa tgacaaaata 125580
gagcatgaat tggaggagat ggtggacaaa ggtaccgtac cttcttattt gtatcatctg 125640
tccatcaacg tcatttcaat aatattggat gatataaatg gaactcgtta atattttttt 125700
agaaacggat gctggaagag taaagtttgc cataaaaaat accgacgatg tatgtgcctc 125760
ggagttaata aataaatttg tggaactgtt aagtgaatac attcacattg accaatcaga 125820
attttatttg gtggtaaagg ataaggatat tttttatttt aagtgtgata gggggtctat 125880
ttcgattgta aacaatgagt tttatgtctt tgacgaaccc ttgctgtttg ttaaagattt 125940
cactaatgta acgggggttg aattcatagt tacagaaacc atgccgtgta gaattatacc 126000
aaaaaataat cacgcggtta tttcagtcgt gactaatcat aagttttata atgggttaag 126060
tttataaagg gttaaccttt gtcacatcga tcgcgtattt gggatcagat gccaaattgt 126120
taaataatct gatgaaaaaa taataaatat aattcagatc atcgctagac atgacattat 126180
tgtcctctat agcgatagtc gcgtgccgtc tacatgcagg acatggaaga gtgctgacta 126240
tagtatatag ttttcgttta cacgcttcta tgttgccgtc taaacccgct tgcgaaagta 126300
ctataaaaat aatggtccat acggctcttc cccaatgttt gggattcatt taaatgaaaa 126360
tatatttcta aattctataa atggatgttc ggtgcattaa ttggtttgaa agtcacggtg 126420
aaaacagatt tttatatctg aaatccagat gtcgaaatgg cgagaccgta tttatacgat 126480
ttcctcatta cttttattac gtagttacgg acgaaatata tcagtcattg tctcctcctc 126540
catttaatgc gaggccgttg ggaaagatga gaactataga cattgacgag acaataagtt 126600
ataatctaga tattaaagat agaaaatgct ccgtcgcaga tatgtggttg atagaagagc 126660
caaagaaacg cagcatacaa aatgccacca tggatgaatt tctcaatatt agttggtttt 126720
atatttctaa cgggatatct ccagacggat gttactcgtt ggacgagcaa tatttgacaa 126780
agattaacaa tggatgttat cattgtgacg atccacgtaa ctgtttcgct aaaaaaatac 126840
ctagattcga tatcccaaga tcgtacttat ttctagatat agagtgtcac ttcgataaga 126900
agtttccttc tgtatttatt aacccaatct cgcatacaag ttactgttat atcgatttaa 126960
gtggtaaacg attattgttt acgctcatta atgaagagat gttaacggaa caggaaatac 127020
aagaagccgt cgatagagga tgtttgagga tacagtcact aatggaaatg gattacgaac 127080
gagaactagt tctatgttct gaaatagttt tgttacgaat agctaaacaa ttgttggaac 127140
taacgttcga ctacgtcgtt acctttaacg gacataactt tgatctgaga tatattacta 127200
atcgtctaga gttattaaca ggagagaaga ttatctttag atctccggac aaaaaggaag 127260
ctgtacatct ctgtatttat gagagaaatc agtctagtca taagggagta ggcggcatgg 127320
ccaatactac gtttcacgtt aataacaata atggaactat atttttcgat ctatattcat 127380
tcattcaaaa atctgaaaaa ttggattcgt acaaattgga ttctatatcc aagaacgcgt 127440
tcagttgcat gggtaaagta ttaaatagag gagttagaga aatgacgttc atcggtgacg 127500
atactacgga cgcgaaaggc aaagccgctg catttgcaaa ggttttaacc acaggtaatt 127560
atgtgactgt tgatgaggat attatatgta aagtaattcg taaagatatt tgggaaaatg 127620
gatttaaagt cgtactatca tgtcctactt tacctaatga tacatataaa ttatctttcg 127680
gaaaggatga cgttgattta gctcagatgt ataaggatta taatctaaac atagctttag 127740
atatggctag atactgtatt catgatgctt gtttgtgtca gtatttgtgg gagtattatg 127800
gagtagaaac aaaaacagac gcgggtgcgt caacatatgt gcttcctcaa tccatggtat 127860
tcgaatatag agcgagtaca gtcatcaagg gtccactgtt aaagctattg ttggaaacta 127920
aaactatctt agttagatca gaaacaaaac aaaagtttcc ttatgaaggc ggtaaggtat 127980
ttgctccaaa acaaaaaatg tttagtaata atgtattaat ctttgattat aacagtctgt 128040
atcctaatgt gtgtatcttt ggaaatctat ctccggaaac attagtcggt gtcgttgtta 128100
gtaccaatag attggaagaa gaaataaata atcagctctt gcttcagaaa tatccacctc 128160
ctagatatat tacggttcat tgtgaaccta gactaccgaa cctcatctct gaaatagcaa 128220
ttttcgatag atcgatagaa ggaaccattc ctagactatt aagaacattt ttggcagaga 128280
gagccagata taaaaagatg ctaaaacagg ctaccagttc aactgaaaag gccatctatg 128340
attccatgca atatacgtac aagatagtag ccaactcagt atatggtctg atgggattta 128400
gaaatagtgc tctatactca tacgcttcgg ctaagagttg cacatccata ggacgtagaa 128460
tgatcttgta tctagaatcg gtactaaatg gagcagagtt atctaacggt atgttacggt 128520
ttgccaatcc attaagtaat ccattttata tggacgatag agatattaat ccgattgtga 128580
aaacatcgtt gcctatagat tacagatttc gttttcgtag cgtgtatgga gataccgact 128640
ccgtgtttac agagatagac agtcaagatg tcgataagtc tatagaaata gcgaaagagt 128700
tagaacgact gattaataat agagtattgt ttaataattt taaaatagag tttgaggcgg 128760
tatataagaa tctgattatg caatcgaaga agaaatatac aacgatgaaa tactcagcat 128820
cgtcgaattc aaaatctgta cctgagagaa ttaataaagg tactagtgaa actagaagag 128880
atgtttccaa gtttcataag aatatgatta agacatacaa gaccagactg tctgagatgt 128940
tgtctgaagg acggatgaat tctaatcagg tatgtataga tattctccgt tctttagaaa 129000
cagatttacg atccgaattt gatagtagat cgtctcctct agaattattt atgttgagtc 129060
gaatgcatca ctcaaattat aaatccgcag ataaccctaa tatgtatttg gttactgaat 129120
ataataaaaa taatccagaa actatagaac ttggagaacg atattatttt gcatatattt 129180
gtccggctaa tgtaccatgg accaaaaaac ttgtaaatat taaaacatat gaaacaatta 129240
tcgatagaag ttttaaactc ggcagtgatc aaagaatatt ttacgaagtt tactttaaac 129300
gattgacgtc cgaaatagtc aatctattgg ataataaagt tttatgcatc tcattctttg 129360
aaagaatgtt tggttcaaaa cctacatttt acgaagcata aaataattta caacagttgt 129420
acgtcgctct ttgttagatt cagtttatcc attagatatt ctacggctgg agtaattttt 129480
gtagtaattg aatacccagg tacgtaaaac aataaaaaca ttaataccgg atcatacttg 129540
gtaaagtaca atatagtact aatattagct aatgtctcat aatcggatgg acttcttgct 129600
ctactaagat tagggtgatc tatatctttg atacttattg gaacgggacc ggtaaatata 129660
taattctctt tgagacgact aaacaaaggc ttatagtctc ctgtttgatg catataccta 129720
gccaacgcca ggtgtttggc attatctgta tagacgtatc tgaataatgt gtgtttagta 129780
atatcaaact gagtattttt aaaccagaac aagatattat agattggaat ggaagtcagt 129840
aacaaaaaac taataaactc gtttgttgga agggcagaaa actttcgaag atatgatacg 129900
tatctaccag agaacgatcc attagcaatg aattcagtat ttactttttc ttcatatacg 129960
ggaataggac ctttatatag agacatgaga aactcgaact ttttaagtaa tcccaacgaa 130020
atgggataat agtcacttgc atctaagttt gcgtatctac tactccaaat tgcagtttct 130080
ggtatccatc catacgcgta attatcaaat agatatgtgt ttttcattaa cggtctactt 130140
agacctctac taaaaaatgt ttcttgatct agaattcttc tttgtgcatt tttgtacacg 130200
tcgtcaaaac gcggaacggt ggcagccata atatttatat cctaccgctt tttatcaact 130260
atgttatgtc ttttagttag gttaatattc taataagatg caggtaatac atcaggttaa 130320
agtattagaa tgggattata cttatatatt tagtttatct ttcatcagat aactaaaaaa 130380
tgtataaaac agacgcgtta cattgcctat gctacatgag ttccatgtgc ggagattgtt 130440
aaagtttagg gtagagagtt gttctagcat ccattcattg tctttacatc cgttatatgt 130500
aattatgtca cccatggaca ttataggttt taatagtact tcagatactg gaataagata 130560
ttgttcgtat atgtgtttga taatcatttg ttgcgtttct ggagaacttt tctctgcatg 130620
atttttacat agctttacaa actcgtgatc actttttata atgagagatc tatagtcttc 130680
gtatctgtta cgaaaatcaa tatattcagg attattttct gaatcacttg attcgtcact 130740
aatatacata actatatgat caacaatttt ttccaaaatc atttctgcat tttctttatt 130800
cattaatttg gtgggagtct gaattgttgc agcagttccc atttatcaaa aatgtgtgat 130860
aattatatct atgtatatac aaattattaa taatatattt ggtctgttct atgatctacc 130920
gtgtcttatc aattgaagta tatatttctt atccgtcttg gttagatgga tgcttttatc 130980
caagaattct tctacatgat atagattatc tctcaaaaac ctttgaaata agacgatgat 131040
ggaaatatta taactagcta aaatagtttt gattagcgat ggaagaatac tagggttttt 131100
atctgtagaa aatcgaacga atgcggatac atcctccaca gacttaagat ggtttatcat 131160
tttaactaac aagtctcctt tataatcatc taacacaaga cctagacgag ccaattgtcc 131220
gtctaaataa tattttaaaa tgtttttgct aaacaagttc agccgtctac tcttggattt 131280
tatagatgac agtttcttta gtattccgtt ctctatgacc atgggatccg actcgtgcaa 131340
aaacaggtat gtattgtatt ccttaacata atacgacgta tcctcgttaa agatttgaca 131400
cttcttcata tcatccattg tatctaatgt gatatcgttc acctcataaa ttatattaga 131460
tatataactg ttattaatat ctaactcatc aaatcgttta atgtccgcag cactcgtaga 131520
gaataaagac ataattcgtt cattatcgaa atattcggga tctatttgaa caacaactct 131580
gaataagtcc tcgttaaacg ttctatcact aataaatgta ttaccgttaa taaaattagc 131640
tttataaaaa ctaataaaat attttttcca atcgtcgttt tttgcatcaa taatagatag 131700
gatatctcca ggaatatcat atatgatttc tagcagaagt tctctgatat ctttttcagg 131760
ctcaaagata taaactaact taagcatgtt tttattaacg cgtccttgtt ttatctcaga 131820
gtatatataa ctaagaattt tatcatacat ggtaatggcg tgtctattaa gaacaatatc 131880
cgcatcatta gctatacttt cgtttaacca cacccaatag ctagtcttat ctccgggaaa 131940
gatataatct ctaaacgttt ctgttagatt gctatggact attctaccag tttgttgaaa 132000
tagagtgtat atatcttgtc tatcattatc cgcaaactct atgcctgtat ctttcttgct 132060
taggtaagcc caaataagta atcttataac acttaatttt ttaacaactt tgaagtctgt 132120
tttcttaaac agttttaaaa aaatgatttc catatctttg atgggttccc ctccgtgaaa 132180
taatggatta agaactaagt cataatttac gcctataagt tctcctaatt cgtccatgta 132240
ttcggcaacc tctaaaaatt tttcatcttg tgttagttta tgcacggttt ccttgtacga 132300
ttgtattgcg ttactaaacg ataaataatt cttagtcaat gctttaacgt acaacgtggg 132360
tgcatcaaat gcgtgtcgta aaaccgcttc gtacacttta caacatcgta ccatatgtat 132420
gaaaacaaaa aaattggtat tagctaatac atccttagta ataacgtgtt gaggaaaatt 132480
gctaactaga tacttgagag ctagtacatg attgagggta aaattgttta ctttacttaa 132540
tgtatcatcc tttaaaaaat ctatattatt ttctactgtg tatataagat actttctacg 132600
aataaaatcc atttttatag aagagagtta tctatgatac tacactctta ttctaataat 132660
tatttttact attttatcac taataactat ttatactatc cattattaat ttaacaattt 132720
gaattagtat tggagaaaga tgaaatgcct attcactaac aaagtcaatg cactcttgaa 132780
gatttttacc aataatatgt agcggattct caaagtattt atttaccatt tctttacaca 132840
gtatcttagc cactggccta cgaacaggca tacatggttc aactatatca tgaacaatgt 132900
ttaattttag tgtatccaat ccaataaatc cattttctac atcatcatcg tatctgtacg 132960
ctttgtattc tccactcttg aacaaatctc taaacagtat cttcaacact ttttccacca 133020
attcctggga tgtcacacat tgttctacca tctgtttgat aaagagggta tcttcttcag 133080
attttccctt gattctatac atgggtttta ggttatacct tgcatctatt gtatatttat 133140
cagattcagc tatcaacatt ttatcaactt gtgttccaat tattctccat ttattagatc 133200
tgcattcatt attatagaat ctttcttcca ctaatattct aataagatta agtttgaaag 133260
gagagaagat cttgtgtttg attttactca ttggatgcat tctataacga atgaatctat 133320
gatcatctcc aaacaaattg ggaaacatgt aaagcagcag agcatatacc atcttactcg 133380
gattctgtga tgctttgccg atggctgaaa tgtccgagaa tagtttataa gttttctgat 133440
tatttggaat agatggtgct atatcttcta gagtagtagt cctaatcatt ctcttaaatt 133500
ttatgtatcc tagtttcaat gtctcgtaat gagtttgtgc tgctcttatt gtctgattta 133560
tttcttttac cattttggct ctattctgaa actttatcct cttcttatcc atttttattg 133620
ttgactccgc actatcgatt tgatactttc ttttcagagt aaagctatcg tcattgatca 133680
tcggacactg acttccactc attatgaaat tgtagccgta taaccacaat acaattatta 133740
acatatatat tcacttttgt taatatcaac ataataatga aaaaatataa atgaacaaag 133800
ttaatacata agtgttataa atggaaaatg tatacattag tagttactca tccaatgaac 133860
aaacatcaat ggcggtagcc gctactgata tccgagaatt actatcacaa tatgtggatg 133920
atgccaactt ggaagactta atagaatggg ccatggaaaa atcatcaaag tactacatca 133980
agaatatagg taatacaaaa tctaatatcg aagaaactaa attcgaatca aagaataata 134040
ttggtataga atactcaaag gattccagaa acaaactatc gtatagaaat aaaccgtcta 134100
ttgccacaaa tttggaatat aaaacactat gtgatatgat taagggtact agcggcaccg 134160
aaaaagaatt ccttcgctat ctcttattcg gtataaaatg cattaagaaa ggagtagaat 134220
acaatataga taaaataaag gatgtgagtt acaacgatta ttttaacgtt ctcgacgaga 134280
aatacaatac accgtgtcct aactgtaaaa gtaggaatac tacgccgatg atgattcaaa 134340
ctagagccgc tgacgaacct ccactagtta gacatgcgtg tagagattgc aaacaacact 134400
ttaagcctcc caaatttaga gcatttcgca atcttaatgt tacaacgcaa tcgatacatg 134460
aaaacaagga aataacagag attcttccag ataataatcc atctcctcca gaatctccag 134520
aaccagcatc acctatagat gacgggttaa tcagatccac attcgataga aacgacgaac 134580
caccagagga tgatgaataa aaaaatgata aaataaatta gttttattgc tggttgtgtt 134640
agttctctct aaaaatgtct aagatctata ttgacgagcg ttctgacgca gagattgtgt 134700
gtgcggctat taaaaacatt ggaatcgaag gagctactgc tgcacaacta actagacaac 134760
ttaatatgga gaagcgagaa gttaataaag ctctgtacga tcttcaacgt agtgctatgg 134820
tgtacagctc cgacgatatt cctcctcgtt ggtttatgac aacggaggcg gataagccgg 134880
atgctgatgt tatggctgac gccataatag atgatgtatc ccgcgaaaaa tcaatgagag 134940
aggatcataa gtcttttgat gatgttattc cggctaaaaa aattattgat tggaaagatg 135000
ctaaccctgt caccattatt aatgagtact gccaaataac taagagagat tggtcttttc 135060
gtattgaatc agtggggcct agtaactctc ctacatttta tgcctgtgta gatatcgacg 135120
gaagagtatt cgataaggca gatggaaaat ctaaacgaga tgctaaaaat aatgcagcta 135180
aattggcagt agataaactt cttggttacg tcatcattag attctgattc tagttatcaa 135240
taacagttag tagtttagtt atacattgaa tcatacatat taattttttt attgagatag 135300
attaaaaaat acaaattgta gtactattaa cgcgactagt atattctcta aagatgatat 135360
ctgtcacaga tattcgtaga gcgtttctag acaatgaatg ccatactatc acaaaagcgt 135420
ttggatatct gcacgaggac aaggctatcg cattaattaa aataggattt catcccactt 135480
atctacccaa agtcctttat aataatgttg tagaattcgt tccagaaaaa ctatatctgt 135540
ttaagccaag aactgtagct ccattggatt tgatatctac tataacaaaa ttaaagaacg 135600
tggacaaatt tgcctcacac ataaattatc acaagaatag tatattgata acaggagaca 135660
agtctctaat tgttaaatgt atgccttaca tgattatttc agatgatgat atacgattca 135720
taagagaaca gtttgttggt acaaattcta ttgagtatat tctatccttc atcaacaagg 135780
aaagcatata tagaatgagt taccaatttt cagagaatga aatagtcact atcatcaata 135840
gagatcattt catgtatgaa ccaatatatg aacatcaggt cttagattct gactttctta 135900
aaactatgtt agatagatac ggaatagttc ccattaattc tggtataata gatgaattat 135960
gtccagaagc tataatagag atattaatgg cagtagttcg tcctagggac gctatccgtt 136020
tcttagatat agtgaataag aatcaattga cagaagatag tgtcaaaaac tatatcatta 136080
atgatatcag aagaggtaaa atagattatt atattccata cgttgaagat tttttagaag 136140
atagaactga agacttggga atatatgcga atatattttt tgaggatgct atagatatta 136200
cgaaactaga catcacaaag acagagttgg aacatatatc gaaatacatg aattattaca 136260
ctacttatat agatcacata gttaacatca tcttacaaaa taattatata gatatcttgg 136320
catctataat agattacgtg caagacgtat taacagaaga attatgtatt agaatagttt 136380
gcgaatcaac aaaccctgtt cccgttacat ctcttcctat acattctacg ttagtaatgg 136440
ttatgtgtat acaaatgaaa tatgtcgata tagttgaatt cttagacgag atcgacatcg 136500
atactttaat agaaaaagga gcagatccga taaccgaata cacatttaca acaagatggt 136560
acaataaaca caatgatttg atcactcttt acattaagaa atatggattc tgtccaatga 136620
tgatgaaacg gttaatgttc gaatatccat tgactaaaga agccagtgat catttactta 136680
aaaccatgga tgaaaacagg ggagctatta tgttttttcc gcgtactatt tgcacacttc 136740
cttatctatt atgttgtaat tataaactaa ttcaaaaacc tattccattc aaagaagaaa 136800
atcgtaacat cgtatataag aaaaccaaca gagtattatg ctttgactcg ttggagaact 136860
ctgcgtttaa aagcctcatt aaaatagatt ctattccagg attaaaaact tataacatga 136920
aagacattac atacgaaaag tctaataata taatttgtgt taggtttata cctcaagaat 136980
caattcataa tgaagagcga agaataaaat tacagttatt cgacattgct agattggcat 137040
cctatggact atattatatt ccctctagat atttatcatc gtggacacca gtagtgaaca 137100
tgatagaggg aagagagtac actaatccac aaaaaataga atgtctagtt attttggatt 137160
tattttcaga ggaattcata gaatatcaaa atctgggcaa tgcggtatct aataaatatg 137220
aactggaata tactatatct aattatcaag ctgccataaa ctgcctaatg agcacgttat 137280
taatatatct agttctagga tcaatcagat cgatatcaaa aactgaagat tttgtattat 137340
ctatattaaa tatcttctat aaaggactga aaattaatga attactttct gaaccagtat 137400
caggagtttg tatcgaatta aataaaataa aagatagagc gagctctgga gacagtagtt 137460
ttatatttct taagaaaaac gagttatcaa aaactctatc gctctgtgaa aaagtttgtg 137520
ttgagaccat attagacaat aatcagagtt ttaaatcctc aaaatgaata ggaatcctga 137580
tcagaatact tttcctaata ttacattaaa gattatagaa acctatttag gcagagtacc 137640
tagtgtgaac gaatatcata tgttaaaatt acaagctaga aatattcaga aaataactgt 137700
ttttaacaaa gacatatttg tatctttagt aaaaaagaat aaaaaaagat ttttttccga 137760
tgttgataca tctgcatcag aaataaaaga tcgtatactt agctactttt ctaaacagac 137820
tcaaacatat aatataggta aattatttac gattatagaa ctacaatctg tattagtgac 137880
cacatacacg gacatattag gagttcttac tattaaagct ccaaatgtaa tttcatctaa 137940
aatttcttat aatgtaacat caatggaaga attggcaaga gatatgctaa attctatgaa 138000
cgtcgcagta atagacaagg caaaagtaat gggacgtcat aatgtatctt ccctagtcaa 138060
aaatgttaat aagttgatgg aagaatatct tagacgccat aataaaagtt gtatatgtta 138120
cggatcatat tctctatatc taattaatcc aaatatacgg tacggcgata tagatattct 138180
tcaaactaat tcgaggactt ttcttataga tttggcattt ctaataaaat ttattacggg 138240
aaataatatt atattaagta aaatcccata tcttagaaac tatatggtga taaaagatga 138300
aaacgataat catatcattg atagttttaa tattcgccag gataccatga acgtagttcc 138360
taaaatcttt atagataata tctatatagt ggatccgacg tttcaactat tgaacatgat 138420
aaaaatgttt tctcaaatag atagattgga agatctatcc aaagatcctg aaaagtttaa 138480
tgcgcgtatg gcaaccatgc tagaatacgt tagatataca catggtatag tctttgatgg 138540
taagcgtaat aatatgccga tgaaatgtat catcgatgaa aataatcgca tagttactgt 138600
tactactaaa gactatttta gctttaaaaa atgtctagtg tatctagatg aaaatgtgtt 138660
atcgagtgat atattagatc ttaacgccga cacatcgtgt gatttcgaga gtgttacaaa 138720
ttctgtatat ctaattcatg ataatatcat gtatacatat ttctcaaata ctattctcct 138780
tagtgataag gggaaggtac atgaaataag tgccagaggt ttatgtgcac atatattgtt 138840
gtatcagatg ctgacatctg gagaatacaa acaatgttta tcggatctct taaattcgat 138900
gatgaataga gataaaatac ctatctattc acatactgaa agagataaaa aacctggacg 138960
acacggattt attaatatcg aaaaggatat aattgtattt taggacaaaa gtctagaagc 139020
tacattatcg cgattagccg cgaacatatt ttgtagcatg tccgtcctca taaacggaac 139080
ttgttttcct gggttattca ttctctcgca tctggaaggg gacgaaggtc ttctctcaca 139140
cgcgggtgat gagggtttat ctactttgag tacgcaggaa gctttacttc cttcgcattc 139200
tacagttcta acatcgcata ctttaacggc ttttagaacc agatatcttc cttctttggt 139260
attgatataa aacggagtat gagcagatgc aaaatgagaa ttcatttata gcatagaaaa 139320
aaaacaaaat gaaattctac tatattttta catatatata ttctaaatat gaaagtggtg 139380
attgtgacta gcgtagcatc gcttctagac gcatctattc agtttcaaaa aacggcatgt 139440
aggcatcact gtaattacct atctatgcaa gtagttaaag agatagaaga atttggtact 139500
atcaatgaaa aaaatttgga atttgacact tggaaagacg ttatacaaaa cgatgaaata 139560
gatgcattag tattttatag agtaaaacaa attagtattt ctacgggtgt tctatataaa 139620
tctatgatgc gcaatagaac aaaacctatt tccatgtact ttgtacgtga ttgtctggca 139680
tttgatggag atcctccgtc ttttagaatg acgtcttgca atatcaacgc atacaatcgt 139740
agtaagatta aagatttaat aatcctaatg aatatgaaaa catgtaataa aaaaattatc 139800
ggtgagttta taatagacaa ttttggaagc gtcgatgcat tactatcgat agttaattcc 139860
aatgttacgt ggattacatc agttataaat aatagtaacg gcaggggtat taatatcagg 139920
gtatcaaata ataaaatgtt aactataact agttttcgac gattcgtcaa taaacttaaa 139980
atgtacaaaa ctactaaatg cgcttctcaa ttggataatc tatgtaccga gatgaacaaa 140040
atggatatta tagacaaaaa atgaaacgta atgaggagta ttgcggggct acataaatta 140100
aaaatggaaa tttttaatgt agaagaattg ataaatatga aaccttttaa gaatatgaat 140160
aaaataacaa ttaatcaaaa tgataattgt atattagcaa atcgatgctt tgttaaaata 140220
gatactccta gatacatacc atcgacatcc attagcagtt ctaatatcat cagaatacgg 140280
aatcatgatt ttacattatc tgaattattg tattcaccgt ttcattttca acagcctcag 140340
tttcaatatc tccttcctgg gtttgtatta acgtgtattg ataaagtttc gaaacagcaa 140400
aaaaaatgta aatattgtat ctctaatcgt ggagatgatg atagtttaag cattaatcta 140460
tttattccga ctattaacaa gtctatatat attattatcg gtttacggat gaaaaatttt 140520
tggaagccta aattcgaaat agaataatgt ttttatatta tacatgttct aaaagaataa 140580
tcgatacagt ttaagtgaaa gctagagagg ggtttttaaa tggtcatcgg tttagtcata 140640
ttcgtgtctg tggcggccgc catcgtcggt gtgttgtcta acgtattgga catgtttatg 140700
tacgtagaag aaaataatga agaggatgct agaatcaagg aggagcaaga actactgttg 140760
ctatattgat acataattga aaatctacca acttaaatac accgcctata aatttacaat 140820
gaaacacaga ttgtattctg aaggattgag tattagtaat gatttaaact cgataatcgg 140880
tcaacaatct acaatggata cggatataga aatagacgaa gatgacatca tggaacttct 140940
taatatattg actgagttag gttgtgatgt cgactttgat gaaaatttta gcgatatagc 141000
cgatgatatt ctagaatcgt tgatagaaca ggatgtataa gtttttatgt taactaaatg 141060
tggccatttg caccggtacc tgcgggagca aaatgtaggc tggtagaaac actaccagaa 141120
aatatggatt ttagatccga tcatttaaca acatttgaat gttttaacga aattatcact 141180
ctagctaaga aatatatata catagcatct ttttgttgta atcctctgag tacgactagg 141240
ggagcgctta tttttgataa actaaaagag gcatctgaaa aagggattaa aataatagtt 141300
ttgctagatg aacgagggaa aagaaatctg ggagagctac aaagtcactg cccggatata 141360
aattttataa ccgttaatat agataaaaaa aataatgtgg gactactact cggttgtttt 141420
tgggtgtcag ataatgaaag atgttatgta ggaaacgcgt catttactgg aggatctata 141480
catacgatta aaacgttagg tgtatattct gattatcccc cgctggccac agatcttcgt 141540
agaagatttg atacttttaa agcctttaat agcgcaaaaa attcatggtt gaatttatgc 141600
tctgcggctt gttgtctgcc agttagcact gcgtatcata ttaagaatcc tataggtgga 141660
gtgttcttta ctgattctcc ggaacaccta ttgggatatt ctagagatct agacactgat 141720
gtagttattg ataaactcaa gtcggctaag actagtatag atattgaaca tttggccata 141780
gttcccacta cacgtgtcga cggtaatagc tactattggc ccgacattta caactccatt 141840
atagaagcag ccattaatag aggagttaag atcagacttc tagttggtaa ttgggataag 141900
aacgacgtat attctatggc aaccgccaga agtctagacg cgttgtgtgt tcaaaatgat 141960
ctatctgtga aggttttcac tattcagaat aatacaaaat tgttgatagt cgacgacgaa 142020
tatgttcata tcacttcggc aaatttcgac ggaacccatt accaaaatca cggattcgtc 142080
agttttaata gtatagataa acagcttgta agcgaggcta aaaaaatatt tgagagagat 142140
tgggtatcta gccacagtaa atcgttaaaa atttaaaaaa tagaaacgta tagaacgcca 142200
tcatgttaaa caggatacaa accttgatga aaacagctaa caattatgaa actattgaga 142260
tattgcgtaa ctatttaaga ctgtatatca ttttggcacg aaatgaagaa ggtcatggta 142320
tactaatata cgatgataac atagatagtg ttatgtcgat gatgaatatt acaatattag 142380
aagttatagg attgacgact cattgcacaa aattaagatc atcgcctcca attcctatgt 142440
ctagattgtt tatggacgaa atagatcatg agtcatatta ttctccaaaa acttcagatt 142500
atccgttgat cgatattata cgaaagcgtt ctcacgaaca gggagatata gcactggctt 142560
tagaacgata cggtattgag aatacagatt ccatatcaga aattaatgaa tggttgtcgt 142620
caaaaggttt agcatgttat agatttgtaa aatttaacga ttataggaaa cagatgtatc 142680
gtaagttctc taggtgtact atagttgaca gtatgataat agggcatata ggtcatcatt 142740
atatttggat taaaaattta gaaacatata cgcgtcccga aattgatgtg ttaccgtttg 142800
atattaaata catatctaga gatgaattgt gggcgcgaat ttcttcctcg ttagatcaaa 142860
cacatataaa aaccatcgcc gtatcagttt atggagctat tactgataat ggaccaatac 142920
catatatgat atccacgtat ccgggtaata cctttgttaa ctttaacagt gtaaaaaatc 142980
taattttaaa tttcttagat tggattaaag atattatgac tagtacacga actatcattc 143040
tagtaggtta catga 143055
<210> 45
<211> 31690
<212> DNA
<213> 人工序列
<220>
<223> 载体
<400> 45
tggctggaat cattaacaag aaaataaaaa acaatttcaa agttaaacat aactggtatt 60
acgatttcca tttctttgtt catactttat taaaaacata tccagaaatc gaaaaagata 120
tcgaatttag tacggcattg gaagaattca tcatgtgtac caaaacagac tgtgataaat 180
atagattaaa ggtttccatt cttcacccaa ttagtttctt ggaaaaattt attatgagag 240
acattttctc agactggata aatggcggaa actaaagagt ttaaaacttt gtataatctt 300
tttatagata gttatttaca aaaattagct caacattcta tccctactaa tgtcacttgt 360
gctattcata taggagaggt tataggacag tttaaaaatt gcgcgctccg aataactaac 420
aaatgcatga gtaattctcg acttagtttc acactcatgg ttgaatcatt tattgaagtg 480
atttcattgc ttccggaaaa ggatagaaga gctatcgctg aggaaatagg aatagatcta 540
gacgatgtac ctagtgcggt atccaagcta gaaaagaact gtaatgcgta tgcggaggtt 600
aataatatta tagatataca gaaattggat atcggagaat gttcggctcc gcccggtcaa 660
catatgcttt tacagatagt taatacagga tccgcggaag caaattgtgg tttacagaca 720
attgttaagt ccttaaataa aatatacgtt ccacctatta tcgaaaaccg attgccgtat 780
tacgatccgt ggtttctagt gggtgtagca attattctag ttatttttac tgtagctatt 840
tgttctatta gacgaaatct ggctcttaaa tacagatacg gaacgttttt atacgtttaa 900
ttaataaaaa aatttaatta caaggtataa aatagtactc catctacgca atcgcgataa 960
tggagggatc taaacgcaga cacgacagtc ggcgactaca acaagaacag gagcagcctc 1020
gtccacgtac accgccatca tatgaagaaa ttgcaaaata tggacactca tttaacgtga 1080
aaagatttac gaatgaagaa atgtgtctta agaatgatta tccacgaatt atatcatata 1140
atcctccacc aaaatagagt atatatatat catcatttca tgatgtatac tactgacata 1200
gtttcaatgt gaacttttca ctttcttgcc ggttatgaag aatattttta ttttaatggt 1260
cattactaat cgtatattat aattgaaaat ggattagttt aatatgacgc tcgtcatggg 1320
atcctgctgt ggtagattct gtgacgctaa gaataagaat aagaaggaag atgtagaaga 1380
gggaagagaa ggatgttaca attataagaa ccttaatgat ctggatgaat ccgaagcacg 1440
tgtagaattt ggaccattat atatgataaa tgaagaaaaa tcagacataa atacattgga 1500
tataaaaaga agatatagac acacgataga gtctgtatat ttctaaaagt ttttataaaa 1560
aatgagtaaa atactcacgt ttgttaaaaa taagataatt gacttgatta ataatgacca 1620
aattaaatat tctagagtta taatgataga agagtccgat agtcttttac cggttgatga 1680
ggtgcatgct aaccacggat ttgactgtgt ggagatgata gatgaaaata taagcaatga 1740
gaatatcgaa cagtataaaa ccgaatcttt ttttacaata aattgaaatc aaaacattta 1800
ttaaaccgca tcaagatggg tacgaacggc gttagagtat ttgtcatttt atatttgttg 1860
gctgtatgcg gatgtatcga atacgacgta gacgataatg tacatatttg tacccacact 1920
aacgtgtcac atattaatca cactagttgg tattataatg ataaggttat agcgctagcc 1980
accgaggata aaacttctgg ttatatatca tcattcataa aacgcgttaa tatctcatta 2040
acttgtttaa atatatcgag tttgaggtac gaagattctg gtacatacaa aggagtatcg 2100
catctaaaag atggagtcat cgttacgact actatgaata tatctgtaaa ggctaatatc 2160
attgacttga ctggtagagt gcgttatcta accagaaatt attgcgaagt taaaatacga 2220
tgcgaaataa catctttcgc gcttaatggt tctactacac caccacatat gatattagga 2280
acagtagata aatggaaata tcttccattt cctacagatg attatagata cgtaggggaa 2340
ctgaaaagat atatatctgg aaacccatat ccaacagagt cgctagcgtt agaaattagc 2400
tcgacgttta atcggtttac tatcgttaaa aatttgaacg atgacgagtt ttcttgttat 2460
ctgtttccat aaaatgttga acgcgcgcca tatttgtgaa tccgaatggg aggctttaaa 2520
taataataac gataattcat cctccatgcc cgcttcccac aacaatctcg caaacgattt 2580
atctagtatg atgtcacaat tacaaaatga taataacgat aatttaatta tgatagtact 2640
aataacaatg ctatcaataa tacttgtaat tattgtagtg attgcggcga tatcgatgta 2700
caaaagatcc aagtacaggc atatagataa ctgaaaaaaa atttattgtt attgttaatt 2760
tagttatgga acccatcctt gcaccaaatc caaatagatt tgttattttc ccaatccaat 2820
atcatgacat ctggaacatg tataaaaagg cagaggcatc attttggaca gtggaagaag 2880
tagatatatc taaagatatc aatgattgga ataaactaac accagacgaa aaatatttta 2940
taaaacatgt attggcgttt tttgcagcca gtgacggaat agtgaatgaa aatttggcgg 3000
aacgattttg tacagaagta cagattaccg aggctagatg tttctacgga tttcagatgg 3060
ccattgaaaa cattcattcg gaaatgtata gtcttttgat cgatacttat gttaaagata 3120
gtaatgaaaa aaactatctc tttaatgcca tagaaacgat gccttgtgta aaaaagaagg 3180
ccgattgggc tcaaaagtgg atacatgaca gcgccggtta tggagagaga cttattgcct 3240
ttgctgcagt agaaggaatc ttcttttccg gatcattcgc ttccatattt tggcttaaaa 3300
agcgtggcct aatgcccgga ctcacgtttt ccaacgaatt gattagtaga gacgagggtc 3360
tacactgcga cttcgcatgt ttgatgttta aacatttatt gcatccaccg agtgaagaaa 3420
ccgttagatc tattataaca gatgcggtat ccattgaaca agaatttctt actgcggctc 3480
ttccagttaa acttatagga atgaattgtg aaatgatgaa aacatatata gaattcgtcg 3540
cggatagatt gatttctgaa ttgggattta aaaaaattta taatgttacc aatccgtttg 3600
atttcatgga aaatatatca ttagaaggta aaactaattt tttcgaaaaa cgtgtgggtg 3660
aataccaaaa aatgggagtt atgtctcaag aagataatca tttttcttta gatgttgact 3720
tttaaagaaa cataaatgcc gatatttgtc aatactgtgt actgtaagaa tatattagca 3780
ttgtctatga ctaagaaatt caaaacaatt attgatgcca taggaggcaa tataatagtc 3840
aattctacga tattgaaaaa gttatctcct tactttcgca cacatttacg tcaaaaatac 3900
acgaaaaata aagatccagt tacgagggtt tgtctagacc ttgacattca cagtctaact 3960
tctatagtta tttactcata tactggaaag gtatatatag atagtcataa cgtcgtcaat 4020
ttattacgtg cttctatatt aacctctgta gaatttatca tctacacttg tataaacttt 4080
atcctacgag attttagaaa ggaatattgt gtcgagtgtt acatgatggg tatagaatac 4140
ggactatcca atctcttatg tcatactaaa aactttattg ccaaacactt tttggaactg 4200
gaagatgaca tcatagacaa ttttgattat ctatctatga aacttattct agaaagcgat 4260
gaactaaatg ttccagatga ggattttgtc attaagtggt atataaagcg aagaaataaa 4320
ttaggaaatc tgctactcct tatcaaaaat gtaatcaggt caaattatct ttctcccaga 4380
ggtataaata atgtaaaatg gatactagac tgtaccaaaa tatttcattg tgataaacaa 4440
ccacgcaaat catacaagta tccattcata gagtatccta tgaacatgga tcaaattata 4500
gatatattcc atatgtgtac aagtactcat gttggagaag tagtatatct catcggtgga 4560
tggatgaaca atgaaataca taacaatgct atagctgtaa attatatatc aaacaattgg 4620
attccaattc ctccgatgaa tagccccaga ctgtatgcta gcgggatacc cgctaacaat 4680
aaattatacg tagtaggagg tctaccaaat cccacatctg ttgagcgttg gttccacggg 4740
gatgctgctt gggttaatat gccgagtctt ctgaaaccta gatgtaatcc agcagtggca 4800
tccataaaca atgttatata cgtaatggga ggacattctg aaactgatac aactacagaa 4860
tatttgctac ccaatcatga tcagtggcag tttggaccat ccacttatta tcctcattat 4920
aaatcatgcg cgttagtgtt cggtagaagg ttattcttgg ttggtagaaa tgcggaattt 4980
tattgtgaat ccagcaatac atggactctg atagatgatc ctatttatcc gagggataat 5040
ccagaattga tcatagtgga taataaactg ctattgatag gaggatttta tcgtgaatcg 5100
tatatagata ctatagaagt gtacaatcat cacacttatt catggaatat atgggatggt 5160
aaataatttt gaaataaaat attagtttta tgttcaacat gaatattaac tcaccagtta 5220
gatttgttaa ggaaactaac agagctaaat ctcctactag gcaatcgccg ggtgctgccg 5280
gatatgattt gtatagcgct tacgattata ctatccctcc aggagaaaga cagttaatta 5340
agacagatat tagtatgtcc atgcctaaga tttgctatgg tagaatagct cctaggtctg 5400
gtctgtcact aaaaggcatt gatataggag gtggtgtaat agacgaagat tataggggaa 5460
acataggagt cattcttatt aataatggaa aatgtacgtt taatgtaaat actggagata 5520
gaatagctca gctaatctat caacgtatat attatccaga actggaagaa gtacaatctc 5580
tagatagtac aaatagagga gatcaagggt ttggatcaac aggacttaga taataaacaa 5640
tagtatgttg tcgatgttta tgtgtaataa tatcgtagat tatgtagatg gtatagtaca 5700
ggatatagaa gatgaggcta gcaataatgt tgatcacgac tatgtatatc cacttccaga 5760
aaatatggta tatagatttg acaagtccac taacatactc gattatctat caacggaacg 5820
ggaccatgta atgatggctg ttcgatacta tatgagtaaa caacgtttag acgacttgta 5880
tagacagttg cccacaaaga ctagatcata tatagatatt atcaacatat attgtgataa 5940
agttagtaat gattataata gggacatgaa tatcatgtat gatatggcat ctacaaaatc 6000
atttacagtt tatgacataa ataacgaagt taatactata ctaatggata acaaggggtt 6060
gggtgtaaga ttggcgacaa tttcattcat aaccgaattg ggtagacgat gtatgaatcc 6120
agtaaaaact ataaaaatgt ttactctact atcgcatact atatgcgatg attgttttgt 6180
agattatata acggacattt caccaccaga taataccatc cctaacacta gcacgcgtga 6240
atatctaaag cttattggca tcacagctat catgtttgct acatataaaa ctctcaaata 6300
catgatagga taattttttt taacacggat atagaatgct aacgtaataa ttatgcgtta 6360
tgaagacccc tatatcatca attcaatttt ttttctagaa aaagtatcaa gatgtttata 6420
ttatcgtcgg tcatcagatc tgtaatgttt cccaatgatt ggaatctaga ttctgaaatc 6480
tttttgtatc cccaatgttc agtgatttta gcacatattc ctatggtagc gaataaactt 6540
tcctgatcat ggacttttgt aaaattgatg tagtggtctc cttcgctcat agcttcgaca 6600
atctcattaa ttttatcaat accatagtac cgtatagcga catcatcgaa cttcatcaat 6660
tccttgtaca gtcttccaca actggtaata tctttgttaa acactataac atgatttctc 6720
cacgtaatat attcatctat tagatcgatg atggagtcgc gactacatat tttatcatca 6780
tccacaaagt aaaaaacagc atcctcataa tctaatttag tcgccatgac tatctcacaa 6840
aagacagtag ccgtctcctt cctctatatt gatttaattg tatgttttta caattatcaa 6900
taaaacataa aaataatatg atcatcaaac gaactgttaa tattgatagt tatataacgt 6960
gaatcatgag tgcaaactgt atgttcaatc tggacaatga ttacatatcc taaggcatta 7020
gtattcataa gtcatggagc tggtaaacat tctggacgtt atgacgaact agctgaaaac 7080
atatcatcgt taggaatttt agtattctca catgatcata ttggacatgg aagaagtaat 7140
ggtgaaaaaa tgatgattga tgactttggt acagcacgtg gtaactatta aatctactta 7200
ttgggtcatt ccatgggagc aacaatttct atactagcct cttacgataa tccaaacttg 7260
tttacagcaa tgattctaat gtctcctcta gttaatgcag atgctgtttc aagactgaat 7320
ctgctagctg ccaaacttat gggaaccatc acaccaaatg cgccagtcgg aaagctatgt 7380
ccagaatcag tatctagaga tatggataaa gtttataaat accaatacga cccattaatc 7440
aatcatgaaa aaattaaggc tggatttgct agtcaggtct tgaaggctac caacaaggtt 7500
agaaaaataa tttccaagat taacaccccg actctcatac tccagggaac aaacaatgag 7560
attagcgatg ttttaggtgc atattatttc atgcaacatg caaattgtaa tagagaaata 7620
aaaatttatg aaggtgccaa acatcatctt cataaggaaa cggatgaagt taaaaaatca 7680
gtcatgaaag aaatagaaac ttggattttt aatagagtga agtgatatag gattattctt 7740
ttaacaaata aaatgaatcc ggataataca atcgcagtga ttacagagac tattcctata 7800
ggtatgcaat ttgataaagt atatttgtct acatttaaca tgtggaggga aattctatcc 7860
aataccacaa aaacactaga tatatcatct ttttattgga gtttatcgga tgaagtgggt 7920
acgaatttcg gcacgataat attaaacgag attgtacaat tacccaaaag aggagtacga 7980
gttagagtag ccgtcaataa atctaacaaa ccattaaagg atgttgaaag actacaaatg 8040
gccggagttg aagtacgata catagatatt acaaatatcc taggaggagt tcttcataca 8100
aaattttgga tatctgataa tacacatatt tatttaggaa gcgctaacat ggattggaga 8160
tcactaactc aggtcaaaga attgggtatt gcgatcttca ataataggaa cttggcagcg 8220
gatctcactc aaatttttga ggtatactgg tatcttggag ttaacaatct accatataat 8280
tggaaaaact tttatccgtc gtattataat acagatcatc ctcttagtat taacgtaagt 8340
ggtgttccac actctgtatt tattgcttct gcaccgcaac aactatgtac tatggaaaga 8400
accaatgatt taaccgcttt attgtcatgt attagaaatg cgagtaaatt cgtttatgta 8460
tctgttatga actttatccc tattatttat tcgaaggcgg gtaaaatttt gttttggcct 8520
tatatagaag atgaattaag aagatccgct atagacagac aagtatccgt taagctattg 8580
attagttgct ggcaacgatc ttcgtttatc atgagaaact ttttaagatc tatcgctatg 8640
ctaaaatcta aaaacataaa tatagaagta aagctattta ttgtaccaga tgctgatcct 8700
cccattccgt attctagggt aaaccatgcc aaatatatgg taaccgataa aacggcctat 8760
ataggtacct caaattggac aggaaattac tttacggata catgtggagc atctattaat 8820
attacaccgg atgatggatt aggtcttcgt caacaattag aagatatttt tatgcgtgat 8880
tggaattcaa aatacagcta tgaattgtac gatactagtc ctactaaaag gtgtaaacta 8940
ttaaaaaata tgaaacaatg tacaaatgat atatactgcg atgagataca accggaaaaa 9000
gaaattcctg aatattctct tgaataaaat agatataaaa acataatttt tatcccaatt 9060
tacgagcccg ttaacaagat gcttgcattt tgttattcgt tgcccaatgc gggcgatgta 9120
ataaagggca gagtatacga gaatgattat gctctatata tttatctttt tgactatcct 9180
cactctgaag ctatcttggc agagagtgtt aagatgcata tggatagata tgttgaatat 9240
agggataaac tggtagggaa aactgtaaaa gttaaagtga ttagagttga ttatacaaaa 9300
ggatatatag atgtcaatta caaaaggatg tgtagacatc aataattttt ataccgaaca 9360
taaaaataag gttaattatt aataccataa aatcatgatt gcgttattga tactatcgtt 9420
aacgtgttca gcgtctacct atcgtctaca aggatttacc aatgccggta tagtagcgta 9480
taaaaatatt caagatgata atattgtctt ctcaccgttt ggttattcgt tttctatgtt 9540
tatgtcgcta ttgcctgcat caggtaatac tagaatagaa ttattgaaga ctatggattt 9600
gagaaaaaga gatctgggtc cagcatttac agaattaata tcaggattag ctaagctgaa 9660
aacatctaaa tatacgtaca ctgatctaac ttatcaaagt ttcgtagata atactgtgtg 9720
tattaaaccg tcgtattatc aacaatatca tagattcggc ctatatagat taaactttag 9780
acgagatgcg gttaataaaa ttaattctat agtagaacgt agatccggta tgtctaatgt 9840
agtagattct aatatgctcg acaataatac tctatgggca atcattaata ctatatattt 9900
taaaggtata tggcaatatc cgtttgatat cactaaaaca cgcaatgcta gttttactaa 9960
taagtacggt acgaaaacgg ttcccatgat gaacgtagtt actaaattgc aaggaaatac 10020
aatcacaatc gatgacaaag aatatgacat ggtacgcctt ccgtataagg atgctaatat 10080
tagtatgtac ctggcaatag gtgataatat gacccatttc acagattcta ttacggctgc 10140
aaaattagac tattggtcgt ttcaattagg gaataaagtg tacaatctta aactccctaa 10200
attttctatc gaaaataaga gggatattaa gtcgatagcc gaaatgatgg ctcctagtat 10260
gtttaatcca gataatgcgt cgtttaaaca tatgactagg gacccattat atatttataa 10320
aatgtttcag aatgcaaaga tagatgtcga cgaacaagga actgtagcag aggcatctac 10380
tattatggta gctacggcga gatcatctcc tgaaaaactg gaatttaata caccatttgt 10440
gttcatcatc agacatgata ttactggatt tatattgttt atgggtaagg tagaatctcc 10500
ttaatatggg tacggtgtaa ggaatcatta ttttatttat attgatgggt acgtgaaatc 10560
tgaattttct taataaatat tatttttatt aaatgtgtat atgttgtttt gcgatagcca 10620
tgtatctact aatcagatct attagagata ttattaattc tggtgcaata tgacaaaaat 10680
tatacactaa ttagcgtctc gtttcagaca tggatctgtc acgaattaat acttggaagt 10740
ctaagcagct gaaaagcttt ctctctagca aagatgcatt taaggcggat gtccatggac 10800
atagtgcctt gtattatgca atagctgata ataacgtgcg tctagtatgt acgttgttga 10860
acgctggagc attgaaaaat cttctagaga atgaatttcc attacatcag gcagccacat 10920
tggaagatac caaaatagta aagattttgc tattcagtgg actggatgat tcgtattcga 10980
tgattatttt taacaaaata acataaaaat aatatatttt tttaggatgc gatcatgacg 11040
tcctctgcaa tggataacaa tgaacctaaa gtactagaaa tggtatatga tgctacaatt 11100
ttacccgaag gtagtagcat ggattgtata aacagacaca tcaatatgtg tatacaacgc 11160
acctatagtt ctagtataat tgccatattg gatagattcc taatgatgaa caaggatgaa 11220
ctaaataata cacagtgtca tataattaaa gaatttatga catacgaaca aatggcgatt 11280
gaccattatg gagaatatgt aaacgctatt ctatatcaaa ttcgtaaaag acctaatcaa 11340
catcacacca ttaatctgtt taaaaaaata aaaagaaccc ggtatgacac ttttaaagtg 11400
gatcccgtag aattcgtaaa aaaagttatc ggatttgtat ctatcttgaa caaatataaa 11460
ccggtttata gttacgtcct gtacgagaac gtcctgtacg atgagttcaa atgtttcatt 11520
gactacgtgg aaactaagta tttctaaaat taatgatgca ttaatttttg tattgattct 11580
caatcctaaa aactaaaata tgaataagta ttaaacatag cggtgtacta attgatttaa 11640
cataaaaaat agttgttaac taatcatgag gactctactt attagatata ttctttggag 11700
aaatgacaac gatcaaacct attataatga tgattttaaa aagcttatgt tgttggatga 11760
attggtagat gacggcgatg tatgtacatt gattaagaac atgagaatga cgctgtccga 11820
cggtccattg ctagatagat tgaatcaacc agttaataat atagaagacg ctaagcgaat 11880
gatcgctatt agtgccaaag tggctagaga cattggtgaa cgttcagaaa ttagatatag 11940
agaaaatagc tccagaatac agacaatgct tacaggatct ataccatatg aaaattacgc 12000
gtcctagaca ctttgataac tagttatgtc attctcgttt ttatagagtg tactcgttac 12060
taaatattaa ttaatgaaat aataacaatt attaagacat actattcatc caacttaaac 12120
aacgaaaaac atttttcatt aagtttatca tgaatgcgta taataaagcc gattcgtttt 12180
ctttagagtc tgattctatc aaagatgtta tacacgatta tatttgttgg ctcagtatga 12240
ctgatgaaat gagaccatct atcggaaacg tctttaaagc gatggaaacg tttaagatag 12300
acgcggttag atattacgat ggtaacatat acgatttagc taaagatata aatgcgatgt 12360
cattcgacag ttttataaga tctctacaaa atatctcttc aaagaaagat aaactcactg 12420
tttatggaac catgggactg ctgtctattg tcgtagatat taacaaaggt tgtgatatat 12480
ccaatatcaa gttcgctgcc ggaataatca ttttaatgga gtatattttt gatgacacgg 12540
atatgtctca tcttaaagta gcactctatc gtagaataca gagacgtgat gatgtagata 12600
gatatttttt tttcctaaac tgatttctct gtttaaattc gtagcgatat ataaaacaac 12660
atgtaattaa ttaataaact ttaagacatg tgtgttatac taagatggtt ggcttattcc 12720
atagtagctt gtggaattta taaacttatg atagtaaaac tagtacccaa tatgtaaaga 12780
tgaaaaagta aattactatt aacgccgtcg gtattcgttc atccattcag tatgggtata 12840
cagcacgaat tcgacatcat tattaatgga gatatcgcgt tgagaaattt acagttacat 12900
aaaggggata actacggatg caaactaaaa attatttcga atgattacaa gaaattaaag 12960
tttagattca ttatacgccc agattggtcg gaaatcgacg aggtcaaagg attaaccgta 13020
tttgcaaaca actatgcggt gaaagttaat aaggtagatg acacgttcta ttacgtaata 13080
tatgaggctg taatacatct gtataacaaa aaaacagaga tattgattta ttctgatgat 13140
gagaacgaac tctttaaaca ctattaccca tacatcagtc taaatatgat tagtaaaaag 13200
tataaagtta aagaagaaaa ctactcatcc ccgtatatag aacatccgtt aatcccgtat 13260
agagattatg agtccatgga ttaatatgag tatagtgtta aatgacactt actaaatagc 13320
caaggtgatt attcgtattt ttttaaggag taaccatgtc cgcaattaga tttattgcat 13380
gtctatatct catttccatc ttcggaaatt gtcatgagga tccatattat caaccatttg 13440
ataaattaaa cattactcta gatatataca cttatgagga tctagtacca tacaccgtag 13500
acaatgacac aacttctttc gttaagatat actttaaaaa tttttggatt acggttatga 13560
ctaaatggtg tgctccgttt attgataccg ttagcgtata cacatctcat gataatctga 13620
atatacaatt ttatagtagg gacgaatatg atacacaaag cgaggataaa atttgtacca 13680
ttgatgttaa agcacgatgc aaacatctaa caaaacgaga agttacagta caacaagaag 13740
cctacagata ttcattatct tctgacctat cgtgttttga ttctatagat ctagagattg 13800
atcttattga aactaatagt actgacacta cagtactgaa atcatatgag ctcatgcttc 13860
ccaaacgtgc taaatccata cataactgaa atgaaagaaa ccaaaaaatg cgatagcatc 13920
aacaaccaat catggttaac gataagatac tctatgatag ttgtaaaaca tttaacatcg 13980
atgccagcag tgcacaatca ttgatagaaa gtggtgcaaa tccattatat gagtatgatg 14040
gtgaaactcc attaaaggca tacgttacca agaaaaataa taatatcaaa aacgatgttg 14100
tgattttgtt attgtcgtca gtcgactata aaaatatcaa tgattttgat atactcgaat 14160
atctatgttc tgataacatc gatatagact tattgaaatt actaatttcg aaaggtatag 14220
aaataaatag tatcaaaaat ggtattaata ttgtagaaaa atacgctaca acatcaaatc 14280
ccaatgtaga tgtgtttaaa ctattattgg ataaaggaat acctacatgt agcaacatac 14340
agtatggata caagatcaaa atagaacaga ttagacgtgc tggtgaatat tataattggg 14400
atgatgaatt agacaattac gattacgact acaccactga ttatgatgat agaatgggta 14460
aaacagttct ctattattat attattacta ggtcacaaga tggttatgct acatctttgg 14520
acgtaataaa ctatttaatt tcacacgaaa aagagatgcg ttattatact tatcgtgaac 14580
ataccacact ctattattat cttgacaaat gcgatattaa acgggaaata tttgacgcgt 14640
tattcgatag taactatagt ggtcatgaac taatgaatat tctatctaac tatttacgta 14700
aacagtttag gaagaaaaat cacaaaatcg ataattatat agttgatcaa ctattattcg 14760
accgtgatac gttttatatt ttagaattgt gtaatagttt acgtaataat atccacaatt 14820
cttaaaagat atacagattc tatacaagat ctattgttag aatatgtatc ttatcataca 14880
gtatacatca atgttattaa atgtatgatt gatgaaggag ctacattata tagatttaag 14940
catataaata aatattttca aaaatttggc aatagagatc ctaaagttgt cgagtatatt 15000
ttaaaaaatg gaaacttagt tgtagataat gacaatgatg ataacctaat aaatattatg 15060
ccattattcc ctaccttctc tatgcgtgag ttggatgtgt tatcgatact aaaactttgt 15120
aagccgtata ttgatgatat aaacatggat gtagtatact ttatcattgt attaagtcgc 15180
atagtgtcag cctagtagaa tggttaatag ataatggcgc agacattaat ataataacaa 15240
aatatgggtt tacatgtatt actatttgtg ttatactggc agataaatat atcccagaaa 15300
tagcagaatt atatattaag atattggaaa ttattctgag taaattacca accatcgaat 15360
gtattaagaa aacagttgat tacctagacg atcacaggta cttattcata ggtggtaata 15420
ataaatcgtt actgaaaata tgtatcaagt acttcatatt agtcgattat aagtacacat 15480
gtagcatgta tccatcatat atagaattta taaccgactg cgaaaaagaa attgcggata 15540
tgcgtcaaat taaaataaat ggtacggaca tgcttacagt gatgtacatg ttaaataaac 15600
ctacaaagaa acgatatgtt aataatccga tatttacaga ttgggctaat aagcaatata 15660
agttttataa tcaaataata tataatgcta ataagttaat agaacaaagt aagaaaatag 15720
acgacatgat agaggaggta tccattgacg ataatcgttt atcaacacta ccgttagaaa 15780
ttagacattt gattttctcg tacgcgttcc tataaaaata gaaactataa tcatataata 15840
gtgtaggttg gtagtattgc tcttgtgact agagacttta gttaaggtac tgtaaaaata 15900
gaaactataa tcatataata gtgtaggttg gtagtagggt actcgtgatt aattttattg 15960
ttaaacttgt ccttaagtct tattaatatg tcttctaaag ggggtagtgg cggcatgtgg 16020
agtgtcttta tccatggaca tgatggtagt aataaaggat ctaaaactta tacatctggt 16080
ggcggtggaa tgtggggagg aggatcgtcc agtggtgtaa aaagtggggt taacggaggt 16140
gtaaaatctg gaactggtaa aatttaaaca ctaaattatt tttattaata attgtacaag 16200
tttttgacat gatatttaat gacattagtt gtgtgggtgt atagagttca cagtagctca 16260
ttcagtcaaa atgtttgact atttggaaaa tgaggaggtg gctctcgatg aacttaaaca 16320
gatgttgaga gacagagatc ctaatgatac caggaaccaa ttcaagaata atgctttaca 16380
cgcatacctt tttaatgagc attgtaataa tgtcgaggtc gtcaaactac tactagacag 16440
tggcactaat ccattacgca aaaattggag acagctaccc cattagaaga atacacaaat 16500
agtagacatg ttaaagttaa aggatatagc gatggctcta ctagaagcca ctggatttag 16560
caacataaat gactttaata tattcagcta tatgaaatcc aaaaatgtag acgttgactt 16620
gataaaggtg ttggtagaac atggatttga cttgagtgtt aaatgtgaaa accatcgttc 16680
agttatagaa aattatgtaa tgacagatga tcctgttcct gaaattattg atttgttcat 16740
agaaaatggc tgcagtgttc tttatgagga cgagtactga tacgcgtatg atgattatca 16800
actacgaaat tgcggtaccg tattgcatct gtatatcatc tctcatctgt attcagagtc 16860
ggatacgaga gcatatgtgc gtccggaagt tgttaaatgt ctaattaatc acggaatcaa 16920
gccgtctttt atagataaaa actattgtac agctcttcaa tattatatta agtcatctca 16980
tatagatata gacatcgtta aattgttaat gaaaggaata gataacacgg cttattcata 17040
tatagacgat ctaacatgtt gcactcgagt aattatggct gattatctaa atagtgatta 17100
tagatacaat aaagatgtag atttggtcaa attgtttttg gaaaatggaa agccgcacgg 17160
aataatgtgt agtattgtac cactatggag aaatgataag gaaaccatct ttttgatatt 17220
gaaaacaatg aactcggatg tcctccaaca tatactaatt gagtatatga cattcggcga 17280
tatccctcta gtggaatatg gaactgtggt aaataaagag gctatacacg gatactttag 17340
aaatattaat attgattctt acacgatgaa atatctacta aaaaaggaag ggagatgcca 17400
tcaattatct cgatgatgga gagatcccga ttggacacct atgtaaatcc aactatgaat 17460
gttataattt ttacacttat acatacaaaa agggtctttg tgacatgtct tatgcttgcc 17520
caattcttag tactataaac atttgcctac cttatcttaa agacattaac atgattgaca 17580
aacgaggaga aacacttctt cacaaggctg ttagatataa taaacaatct ctagtatctt 17640
tactgctaga atccggttca gatgtcaaca ttagatcaaa taacggatat acatgtatag 17700
ccattgccat caacgaatct aaaaacattg aactgctgaa aatgctatta tgtcataaac 17760
ctacattaga ttgtgtgatt gattcattga gagaaatatc taacatcgta gataacgact 17820
atgctataaa acaatgtatt aaatatgcca tgattataga tgactgtaca tcgtctaaga 17880
ttccagagtc cataagtcaa cgctataatg attatataga tctttgcaat taagaattga 17940
atgagatgaa aaaaataatg gtaggtggta atactatgtt ctcattaata tttactgatc 18000
atggagctaa aattattcat agatatgtca ataatccaga attacgtgag tattatgagt 18060
taaaacaaaa taaaatatat gtggaagcat atgatattat ttccaacgca atagtgaaac 18120
atgatagaat acataaaacc atagaatcag ttgatgataa tacctacatt tctaatcttc 18180
cgtataccat caaatacaaa atattcgagc aacaataagt attttttata cctttaaaat 18240
tgataaataa attttttcta gtgatatttt ggcaagatga aaatcctatt tctcatcgct 18300
ttcatgtatg ggtgtgttca ctcatatgtt aacgcggttg aaaccaaatg tccaaatcta 18360
gacattgtaa catcttctgg agaatttcat tgttcaggat gtgtggaaca tatgcctgag 18420
tttagctata tgtattggtt ggcaaaggat accaagttta tagaacatct gggtgatggc 18480
atcaaagaag atgaaaccgt tcgtaccaca gatagtggaa tcaccactct acgtaaagtc 18540
cttcatgtaa ccgatactaa taaatttgct cattataggt tcacttgtgt cctcactacg 18600
atagatggcg tttcaaaaaa gaatatttgg ctgaagtagt gcgtgctact atttttattt 18660
atgatataat ctaatggaat taatttgaat tgatatttat ccaatactaa agattatatt 18720
agaatcaaat taatctttta tacgagaaaa aataacgaca tacgtcgtca acaaattaaa 18780
ctttttattt attagttaac ttgctcattg ttatgtttct aaaacgggta cgacatatag 18840
gacaattatc cgacgcaccg gtttctcttc gtgttctatg ccatatattg atgcatgtta 18900
tgcaaaatat atgattacac gaatccaata aaccaaagta tctatcgttt tgagtaaaca 18960
acttcatagc aaatttcaca ttctttttct ttacttactc tatacacgtc ctcgtattta 19020
tccagtattt tgatgatatc caactcagaa atggttgttg tattattggg tgtataggta 19080
ttattagcta tgtaccaatt taccaacctt cttaatattg attgataatc acatcggtta 19140
tccaattaat aactaaattg tagtgtatat atagaccata tatgtttcta tttttttgac 19200
agtttcagta agttttgatt gttgtattcc tgtatctcta gataagttag tcatatagtc 19260
ccttccggcg atacgttttt tccaagcccg aaattgatta gccaaatgtg gatttatttt 19320
tgtgataatg catactgtta gtcttatatc atttggttca tctatgtatt gtaatattgt 19380
tacatgatct atagatgatg tattgatttt ggcaggatcg aattccatat ccgcgactaa 19440
acagtgaaaa aaatgtaaat aattttaaat tagtaaaact tttttttatt ttttatgatt 19500
ccaaaaaaac tgaatacaaa gtcctaaatt ataaatatgg agatcatact accacaactt 19560
attattatgt atacaaggcc ggtgtaatag atagatatat ataattctat tacaccggca 19620
gacaattacc gatcggtatt tgtcgttacc aacataccgt ataatatgta atatacaatt 19680
ccataaccca ttgacagttg ttatacatca aaattgcaat tcttttgatt acgatgttat 19740
aagaatgtag ttaattgatg tatgatgtta atgtgtcctc tttcctctta taacatcgta 19800
atcaaaaact tttttataat atatacctaa taatgtgtct taatagttct cgtgattcgt 19860
caaacaatca ttcttataaa atataataaa gcaacgtaaa aacacataaa aataagcgta 19920
actaataaga caatggatat ttacgacgat aaaggtctac agactattaa actgtttaat 19980
aatgaatttg attgtataag gaatgacatc agagaattat ttaaacatgt aactgattcc 20040
gatagtatac aacttccgat ggaagacaat tctgatatta tagaaaatat cagaaaaata 20100
ctatatagac gattaaaaaa tgtagaatgt gttgacatcg atagtacaat aacttttatg 20160
aaatacgatc caaatgatga taataagcgt acgtgttcta attgggtacc cttaactaat 20220
aactatatgg aatattgtct agtaatatat ttggaaacac cgatatgtgg aggcaaaata 20280
aaattatacc accctacagg aaatataaag tcggataagg atattatgtt tgcaaagact 20340
ctagacttta aatcaacgaa agtgttaact ggacgtaaaa caattgccgt tctagacata 20400
tccgtttcat ataatagatc aatgactact attcactaca acgacgacgt tgatatagat 20460
atacatactg ataaaaacgg aaaagagtta tgttattgtt atataacaat agatgatcat 20520
tacttggttg atgtggaaac tataggagtt atagtcaata gatctggaaa atgtctgtta 20580
gtaaataacc atctaggtat aggtatcgtt aaagataaac gtataagcga tagttttgga 20640
gatgtatgta tggatacaat atttgacttt tctgaagcac gagagttatt ttcattaact 20700
aatgatgata acaggaatat agcatgggac gatgatacag atatatggac tcccgtcaca 20760
gaagatgatt acaaatttct ttctagacta gtattgtatg caaaatctca atcggatact 20820
gtattcgact attatgttct tactggtgat acggaaccac ccactgtatt cattttcaag 20880
gtaactagat tttactttaa tatgccgaaa taaaaaattt ttgtataata tctagaggta 20940
gaggtattgt ttagataaat acaaataaca tagatacatc gcatatttag catttttata 21000
aatatacata agacatacac tttatacatt tttgtaaaaa tactcataaa aaaaatttat 21060
aaaaattatg gcacaaccat atcttgtata ggtagtttag ttcgtcgagt gaacctataa 21120
acagataata gacaacacgt aataataata atgcctacta atacaagcat aataccggga 21180
gatgggatat atgacgttgt agtgtttggt ttttctgaac gttgatagtc tactaatact 21240
acatgctgac atctaatgcc tgtataacca tgagagcatc tacaatacat accgtcgata 21300
tctctagcgt ggatacagtc accgtgtaaa caatatccat ctccctctgg accgcataat 21360
ctgatagctg gaatatctgt tgtagcgttt gtaatttctg gcgatgtcgt ttcgatagcg 21420
ttaccactat cggcgaatga tctgattatc atagcagcga acaacaacat cagataattt 21480
atcaacattt ttgatggatt ttgtgtttat gctgtttctc agtgtgtgtt tatgacaaga 21540
ttgggaattt tatattatta attcagtaat ataaactaat aatatattgt taattgtgta 21600
aataatataa aaataacaat acaatattga atgtgttgct gttaaaaatg tatgtgttaa 21660
tataatagaa taaaataaat gagtatgatc attttagata acgattgatt ttatcattac 21720
cgcttcattc ttatattctt tgcttacgga acctatattt agaaacatct actaacgatt 21780
ttttatgctt gcattattaa tggtatgtaa taccaatttg ttaagtatga atacggggta 21840
caaacataaa ctgaaattta gatcattaaa tgtttcatca gaaatgactc catgaaaacc 21900
gccgaagaac ttcgtgcaat cattggactt tgtactcaat cagctatcgt ctctggaaga 21960
gtcttcaacg ataagtatat cgacatacta cttatgctgc gaaagattct gaacgagaac 22020
gactatctca ccctcttgga tcatatccgc actgctaaat actaaatctc cttcatgctc 22080
tctcactaca ctttttatca tcttatgagg aataattagc accagaatag ctatggattg 22140
cacatgtatt ctatgtcgtc tactggatga agatgtgacg tacaaaaaaa taaaactaga 22200
aattgaaacg tgtcacaact tatcaaaaca tatagataga cgaggaaaca atgcgctaca 22260
ttgttacgtc tccaataaat gcgatacaga cattaagatt gttcgactgt tactctctcg 22320
cggagtcgag agactttgta gaaacaacga aggattaact ccgctaggag catacagtaa 22380
gcatagatac gtaaaatctc agattgtgca tctactgata tccagctatt cgaattcctc 22440
taacgaactc aagtcgaata taaatgattt cgacttacgt ctgctaaaat acctaattgt 22500
ggataaacgg atacgtccgt ccaagaatac gaattatgca atcaatggtc tcggattggt 22560
ggatatatac gtaacgacgc ctaatccgag accagaagta ttgctatggc ttcttaaatc 22620
agaatgttac agcaccggtt acgtatttcg tacctgtatg tacaacagtg atatgtgtaa 22680
gaactctctt cattactata tatcgtctca tagagaatct ctatccaagg atgtaattaa 22740
atgtttgatc gataacaatg tttccatcca atactactgg tcttgctcaa ccatagatat 22800
agagattatt aataaaggat gtggacacgt gtagagtata cgacgtcagc cctatattag 22860
aggcgtatta tctaaacaag cgatttagag taaccccata taatgtagac atggaaatcg 22920
ttaatcttct tattgagaga cgtcatactc ttgtcgacgt aatgcgtagt attacttcgt 22980
acgattccag agaatataac cactacatca tcgataacat tctaaagaga tttagacaac 23040
aggatgaatc catcgtacaa gccatactga taaactactt acattacggc gatatggtaa 23100
gtatacctat cattcaatgc atgttggata agacgacgga caacaacttt gttaataata 23160
atctcgtcga tgtaaacgtc gtaaggttta tcgtggaaaa tatggacacg cggctgtaaa 23220
tcacatatct aacaatggcc gtctatgtat gtacggtctg atattatcga gatttaataa 23280
ttgcgggtat cactgttatg aagatgtatt tgatatacta agcaagtaca tggatgatat 23340
agatatgatc gataactcta ctatattacg cggtcgatgt caataatata caatttgcaa 23400
agcggttatt ggaatatgga gcgagtgtca cgctcgataa tcaatacggc catccagaaa 23460
agcagttacc aaagagaagc tagttgattt attactgagt taccatccca ctctagagac 23520
tatgattgac gcatttaata gagatatacg ctatctatat cctgaaccat tattcgcctg 23580
tatcagatac gccttaatcc tagatgatga ttttccttct aaagtaagta tgatatcgcc 23640
ggtcgtcata aggaactaaa gcgctataga gcagacatta atagaatgaa gaatgcctac 23700
atatcaggcg tctccatgtt tgatatatta tttaaacgaa gcaaacgcca cagattgaga 23760
tacgcaaaga acaatgagag gatcgactcc attaaataat ttatcatgga gtgataatgt 23820
cctgtttcca tggcatatta caaaatcgat tccgtccaag atgataaaaa catttaccgg 23880
catcataaac acggagttta ttttatatgt ctcgcataaa cattactaaa aaaatatatt 23940
gttcggtttt ctttcacatc tttaattatg aaaaagtaaa tcattatgag atggacgcat 24000
cgttcgcgac agtatgtggt acatacctaa cgtatttatg gacgacggta agaatgaagg 24060
tcacgtttct gtcaacaatg tcgacgcgat cgtgtaacac gactcacaat agaatctgtg 24120
aatgctctcc cgatcatgga tgcaaggcat gtgtttccca aacaaaatgt ggaataggat 24180
acggagtatc cggagacgtc atctgttctc cgtgtggtct cggaacatat tctcacaccg 24240
tctcttccgc agataaatgc gaacccgtac ccagaaatac ctttaactat atcgatgtgg 24300
aaattaacct gtatccagtt aacgacacat cgtgtactcg gacgaccact accggtctca 24360
gcgaatccat ctcaacgtcg gaactaacta ttactatgaa tcataaagac tgcgatcccg 24420
tcttcttaat aaggtagcga cttcaggttt ctttacagga gaaaggtgtg cactctgaat 24480
ttcgagatta aatgcaataa caaagattct tcctccaaac agttaacgaa agcaaagaat 24540
gatactatca tgccgcattc ggagacagta actctagcgt cgacatctat atactatata 24600
gtaataccaa tactcaagac tacgaaactg atacaatctc ttatcatgtg ggtaatgtag 24660
ccatatgccc ggtagttgcg atatacataa actgatcact aattccaaac ccacccgctt 24720
tttatagtaa gtttttcacc cataaataca ataattaatt tctcgtaaaa gtagaaaata 24780
tattctaatt tattgcacgg taaggaagta gaatcataaa gaacagtact caatcaatag 24840
caatcatgaa acaatatatc gtactggcat gcatgtgcct gccagtcttc agcaatcatc 24900
ctcatcgtgt acggaagaag aaaacaaaca tcatatggga atcgatgtta ttatcaaagt 24960
cacaaagcaa gaccaaacac cgaccgatga taagatttgc caatccgtaa cggaaattac 25020
agagtccgag tcagatccag atcccgaggt ggaatcagtc gaggatgtag atcctcctac 25080
cacttattac tccatcatcg gtggaggtct gagaatgaac tttggattca ccaaatgtcc 25140
tcagattaaa tccatctcag aatccgctga tggaaagact gtgaggtgtc tatcgacatc 25200
agatgtagcg aagaagagaa agacagcgac atcaagaccc atccagtact cgggtctaac 25260
atctctcata agaaagtgag ttacgaagat atcatcggtt caacgatcgt cgatacaaaa 25320
tgtgtcaaga atctagagtt tagcgttcgt atcggagaca tgtgcaagga atcatctgaa 25380
cttgaggtca agtatgtcga cggatcggca tctgaaggtg caaccgatga tacttcactc 25440
atcgattcaa caaaactcaa agcgtgtgtc tgaatcgata actctattca tctgaaattg 25500
gatgagtagg gttaatcgaa cgattcaggc acaccacgaa ttaaaaaagt gtaccggaca 25560
ctatattccg gtttgcaaaa caaaaagtta cctctcgcga cttcttcttt ttctgtctca 25620
atagtgtgat acgattatga cactattcct atttcctttc agggtatcac aaaaatatta 25680
aacctctttc tgatggtctc atacaaaaat atttttattc tctttctctc tttgatggtc 25740
tcataaaaaa tatttttatt ctctttctct ctttgatggt ctcataaaat atttttattc 25800
tctttctctc tttgatggtc tcataaaaaa tatttttatt ctctttctct ctttgatggt 25860
ctcataaaat atttttattc tctttctctc tttgatggtc tcataaaaaa tatttttatt 25920
ctctttctct ctttgatggt ctcataaaaa atattaaacc tctttctgat ggtgtcacta 25980
aaatattttt attctctttc tctcttcaat ggagtcataa aatattttta ttctctttct 26040
ctcttcgatg gtctcacaaa aatattaaac ctctttctga tggtgtcact aaaatatttt 26100
tattctcttt ctctcttcaa tggagtcata aaatattttt attctctttc tctctttgat 26160
ggtctcacaa aaatattttt attctctttc tctctttgat ggtctcacaa aaatattttt 26220
attctctttc tctctttgat ggtctcacaa aaatattttt attctctttc tctctttgat 26280
ggtctcataa aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc 26340
ataaaaaaag ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa 26400
aaagttttac aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaatatt 26460
aaacctcttt ctgatggtgt cactaaaata tttttattct cattctctct tcaatggagt 26520
cataaaatat ttttattctc tttctctctt cgatggtctc acaaaaatat taaacctctt 26580
tctgatggtg tcactaaaat atttttattc tcattctctc ttcaatggag tcataaaata 26640
tttttattct ctttctctct tcgatggtct cacaaaaata ttaaacctct ttctgatggt 26700
gtcactaaaa tatttttatt ctcattctct cttcaatgga gtcataaaat atttttattc 26760
tctttctctc tttgatggtc tcataaaaaa agttttacaa aaatattttt attctctttc 26820
tctctttgat ggtctcataa aaaatattaa acctctttct gatggtgtca ctaaaatatt 26880
tttattctct ttctctcttc aatggagtca taaaatattt ttattctctt tctctcttcg 26940
atggtctcac aaaaatatta aacctctttc tgatggtgtc actaaaatat ttttattctc 27000
attctctctt caatggagtc ataaaatatt tttattctct ttctctcttt gatggtctca 27060
taaaaaaagt tttacaaaaa tatttttatt ctctttctct ctttgatggt ctcataaaaa 27120
aagttttaca aaaatatttt tattctcttt ctctctttga tggtctcata aaaaaagttt 27180
tacaaaaata tttttattct ctttctctct ttgatggtct cataaaaaaa gttttacaaa 27240
aatattttta ttctctttct ctctttgatg gtctcataaa aaatattaaa cctctttctg 27300
atggtgtcac taaaatattt ttattctcat tctctcttca atggagtcat aaaatatttt 27360
tattctcttt ctctcttcga tggtctcaca aaaatattaa acctctttct gatggtgtca 27420
ctaaaatatt tttattctca ttctctcttc aatggagtca taaaatattt ttattctctt 27480
tctctctttg atggtctcat aaaaaaagtt ttacaaaaat atttttattc tctttctctc 27540
tttgatggtc tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat 27600
ggtctcataa aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc 27660
ataaaaaaag ttttacaaaa atatttttat tctctttctc tctttgatgg tctcacaaaa 27720
atattaaacc tctttctgat ggagtcgtaa aaaagtttta tctctttctc cttcgatggt 27780
ctcacaaaaa tattaaacct ctttctgatg gagtcgtaaa aaagttttat ctctttctct 27840
cttcgatggt ctcacaaaaa tattaaacct ctttctgatg gagtcgtaaa aaagttttat 27900
ctctttctct cttcgatggt ctcactaaaa tattttttat tctctttctg atgcatcaac 27960
tatttcttaa acaataacgt ccaacaacat atactcgtcg agcttatcaa catcccctat 28020
gcccatctag gttaccagac aattgtatat cataaaataa tgtttataat ttttacaaaa 28080
atatttttat tctctttctc tctttgatgg tctcataaaa aaagttttac aaaaatattt 28140
ttattctctt tctctctttg atggtctcat aaaaaatatt aaacctcttt ctgatggtgt 28200
cactaaaata tttttattct cattctctct tcaatggagt cataaaatat ttttattctc 28260
tttctctctt cgatggtctc acaaaaatat taaacctctt tctgatggtg tcactaaaat 28320
atttttattc tcattctctc ttcaatggag tcataaaata tttttattct ctttctctct 28380
ttgatggtct cataaaaaaa gttttacaaa aatattttta ttctctttct ctctttgatg 28440
gtctcataaa aaaagtttta caaaaatatt tttattctct ttctctcttt gatggtctca 28500
taaaaaaagt tttacaaaaa tatttttatt ctctttctct ctttgatggt ctcataaaaa 28560
aagttttaca aaaatatttt tattctcttt ctctctttga tggtctcata aaaaaagttt 28620
tacaaaaata tttttattct ctttctctct ttgatggtct cataaaaaaa gttttacaaa 28680
aatattttta ttctctttct ctctttgatg gtctcataaa aaaagtttta caaaaatatt 28740
tttattctct ttctctcttt gatggtctca taaaaaatat taaacctctt tctgatggtg 28800
tcactaaaat atttttattc tctttctctc ttcaatggag tcataaaata tttttattct 28860
ctttctctct tcgatggtct cacaaaaata ttaaacctct ttctgatggt gtcactaaaa 28920
tatttttatt ctcattctct cttcaatgga gtcataaaat atttttattc tctttctctc 28980
tttgatggtc tcataaaaaa agttttacaa aaatattttt attctctttc tctctttgat 29040
ggtctcataa aaaaagtttt acaaaaatat ttttattctc tttctctctt tgatggtctc 29100
ataaaaaaag ttttacaaaa atatttttat tctctttctc tctttgatgg tctcataaaa 29160
aaagttttac aaaaatattt ttattctctt tctctctttg atggtctcat aaaaaaagtt 29220
ttacaaaaat atttttattc tctttctctc tttgatggtc tcataaaaaa tattaaacct 29280
ctttctgatg gtgtcactaa aatattttta ttctctttct ctcttcaatg gagtcataaa 29340
atatttttat tctctttctc tcttcgatgg tctcacaaaa atattaaacc tctttctgat 29400
ggtgtcacta aaatattttt attctctttc tctcttcaat ggagtcataa aatattttta 29460
ttctctttct ctctttgatg gtctcataaa aaaagtttta caaaaatatt tttattctct 29520
ttctctcttt gatggtctca taaaaaaagt tttacaaaaa tatttttatt ctctttctct 29580
ctttgatggt ctcataaaaa aagttttaca aaaatatttt tattctcttt ctctctttga 29640
tggtctcata aaaaaagttt tacaaaaata tttttattct ctttctctct ttgatggtct 29700
cataaaaaaa gttttacaaa aatattttta ttctctttct ctctttgatg gtctcataaa 29760
aaaagtttta caaaaatatt tttattctct ttctctcttt gatggtctca taaaaaaagt 29820
tttacaaaaa tatttttatt ctctttctct ctttgatggt ctcataaaaa atattaaacc 29880
tctttctgat ggtgtcacta aaatattttt attctcattt tctctttctc tcttcaatgg 29940
agtcataaaa tatttttatt ctctttctct ctttgatggt ctcataaaaa atattaaacc 30000
tctttctgat ggtgtcacta aaatattttt attctcattc tctcttcaat ggagtcataa 30060
aaaagtttta tctctttctc tcttcgatgg tctcacaaaa atattaaacc tctttctgat 30120
ggagtcgtaa aaaagtttta tctctttctc tcttcgatgg tctcacaaaa atattaaacc 30180
tctttctgat gcatcaacta tttcttaaac aataacgtcc aacaacatat actcatcccc 30240
tatgcccatc taggttacca gacaattgta tatcataaaa taatgtttat aatttacacg 30300
ttaaaatcat ataataaaac gtagatcgta taatattttt tggtatataa atgatctagt 30360
aaaatccatg taggggatac tgctcacatt ttttctttgg tacaaaattt cacacaagtt 30420
tttatacaga caaattcttg tccatatatt ttaaaacatt gacttttgta ctaagaaaaa 30480
tatctagact aactatctct ttctctttct ctcttcgatg gtctttctga tggagtcgta 30540
aaaaagtttt atctctttct ctcttcgatg gtctcacaaa aatattaaac ctctttctga 30600
tggagtcgta aaaaagtttt atctctttct ctcttcgatg gtctcacaaa aatattaaac 30660
ctctttctga tggagtcgta aaaaagtttt atctctttct ccttcgatgg tctcacaaaa 30720
atattaaacc tctttctgat ggagtcgtaa aaaagtttta tctctttctc tcttcgatgg 30780
tctcacaaaa atattaaacc tctttctgat ggtgtcacta aaatattttt attctctttc 30840
tctcttcgat ggtctcacaa aaatattaaa cctctttctg atggagtcgt aaaaaagttt 30900
tatctctttc tccttcgatg gtctcacaaa aatattaaac ctctttctga tggagtcgta 30960
aaaaagtttt atctctttct ctcttcgatg gtctcacaaa aatattaaac ctctttctga 31020
tggagtcgta aaaaagtttt atctctttct ccttcgatgg tctcacaaaa atattaaacc 31080
tctttctgat ggagtcgtaa aaaagtttta tctctttctc cttcgatggt ctcacaaaaa 31140
tattaaacct ctttctgatg gagtcgtaaa aaagttttat ctctttctcc ttcgatggtc 31200
tcacaaaaat attaaacctc tttctgatgg agtcgtaaaa aagttttatc tctttctctc 31260
ttcgatggtc tcacaaaaat attaaacctc tttctgatgg agtcgtaaaa aagttttatc 31320
tctttctctc ttcgatggtc tcacaaaaat attaaacctc tttctgatgg agtcgtaaaa 31380
aagttttatc tctttctcct tcgatggtct cacaaaaata ttaaacctct ttctgatggt 31440
ctctataaag cgattgattt ttcttaccct ctagagtttc ctacggtcgt tggtcacaca 31500
tttttttcta gacactaaat aaatatttaa aatataatat taatatacta aaatttatgt 31560
attattaatt tataatatta atatactaaa atttatgtat tattaattta tctaactaaa 31620
gttagtaaat catatacata attttataat taatattata tacataattt tataattaat 31680
ttaatcttac 31690
<210> 46
<211> 4590
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 46
cccgccgcca ccatgtctct gctgtggggc ggagtgacag tgctggccgc catgctgatt 60
gctggccagg tggcctccgt ggtgttcctc gtgaaaggcg gaggacctgg cggcggaatg 120
cagctgtttc acctgtgcct gatcatcagc tgtagctgcc ccaccgtgca ggccagcaag 180
ctgtgtctgg gatggctgtg gggaatggac atcgacccct acaaagaatt cggcgccagc 240
gtggaactgc tgagcttcct gcccagcgac ttcttcccct ccatccggga cctgctggat 300
acagccagcg ccctgtatag agaggccctg gaaagccccg agcactgcag ccctcatcac 360
accgctctga gacaggccat cctgtgctgg ggcgagctga tgaacctggc cacttgggtg 420
ggaagcaacc tggaagatcc cgccagccgg gaactggtgg tgtcttacgt gaacgtgaac 480
atgggcctga agatccggca gctgctgtgg ttccacatct cctgcctgac cttcggccgg 540
gaaaccgtgc tggaatacct ggtgtccttc ggcgtgtgga tcagaacccc ccctgcctac 600
agacccccca acgcccctat cctgagcacc ctgcctgaga caacagtcgt gcggcggaga 660
ggcagaagcc ccagaagaag aacccccagc cccagacgca gaagaagcca gtcccctcgg 720
cggagaagat cccagagcag ggaaagccag tgtggcggag gctctggggg aggcatgcca 780
ctgagctacc agcacttcag aaaactgctg ctgctggacg acgaggccgg acccctggaa 840
gaggaactgc ctagactggc cgacgagggc ctgaacagaa gagtggccga ggacctgaac 900
ctgggcaacc tgaacgtgtc catcccctgg acccacaaag tgggcaactt caccggcctg 960
gcctccagca ccgtgcccgt gtttaatccc gagtggcaga cccccagctt cccccacatc 1020
catctgcagg aagatatcat caaccgctgc cagcagtacg tgggccccct gaccgtgaac 1080
gagaagcgga gactgaagct gatcatgccc gccagattct accccaacct gaccaagtac 1140
ctgcccctgg acaagggcat caagccctac taccctgagc acgccgtgaa ccactacttc 1200
aagacccggc actacctgca caccctgtgg aaggccggca tcctgtacaa gagagagaca 1260
accagaagcg ccagcttctg cggcagcccc tacagctggg agcaggaact gcagcacggc 1320
cggctggtgt ttcagaccag cacaagacac ggcgacgagt ctttctgcag ccagagcagc 1380
gggatcctgt ccagatctcc tgtgggccct tgtgtgcgga gccagctgaa gcagagcaga 1440
ctgggactgc agcctcagca gggaagcctg gccagaggca agtctggcag aagcggcagc 1500
atccgggcca gagtgcaccc taccaccaga cggtcctttg gcgtggaacc tagcggcagc 1560
ggccacatcg ataacagcgc cagcagcacc tccagctgcc tgcatcagtc tgccgtgcgc 1620
aagaccgcct acagccacct gtccaccagc aagagacaga gcagctctgg ccacgctgtg 1680
gaactgcaca acatcccccc tagcagcgcc agaagccaga gcgagggccc tatctttagc 1740
gcctggtggc tgcagtttcg gaacagcaag cccgccagcg actacgccct gacccacatc 1800
gtgaacctgc tggaagattg gggccctgcc acagagcacg gcgagcacaa tatccggatc 1860
cccagaaccc ctgccagagt gacaggcggc gtgttcctgg tggataagaa tccccacaac 1920
accaccgaga gcaggctggt ggtggacttc agccagttca gcagaggcag cacccacgtg 1980
tcctggccca agttcgccgt gcccaatctg cagagcctga ccaacctgct gagcagcaac 2040
ctgagctggc tgagcctgga cgtgtccgcc gccttctacc acatcccact gcatcctgcc 2100
gctatgcccc atctgctcgt gggcagttct ggcctgccta gatatgtggc ccggctgtct 2160
agcaccagca gaaacatcaa ttaccagcac ggcaccatgc aggacctgca cgacagctgc 2220
agccggaatc tgtacgtgtc cctcctgctg ctgtacaaaa ccttcggcag aaagctgcac 2280
ctgtactccc accccatcat cctgggcttc agaaagatcc ccatgggcgt gggcctgagc 2340
ccattcctgc tggcccagtt taccagcgcc atctgtagcg tcgtgcggag agccttccct 2400
cactgcctgg cctttagcta catggacgac gtggtgctgg gcgccaagag cgtgcagcac 2460
ctggaatccc tgtttacctc catcaccaac tttctgctgt ccctgggcat ccacctgaac 2520
cccaacaaga ccaagaggtg gggctacagc ctgaacttca tgggctacgt gatcggcagc 2580
tggggcacac tgcctcagga acacatcgtg ctgaagatca agcagtgctt tcggaagctg 2640
cccgtgaacc ggcccatcga ctggaaagtg tgccagcgga tcgtggggct gctgggattt 2700
gccgcccctt ttacccagtg cggctacccc gctctgatgc ccctgtacgc ctgcattcag 2760
agcaagcagg ccttcacctt cagccctacc tacaaggcct ttctgtgcaa gcagtatctg 2820
aacctgtacc ccgtggctcg gcagagaagc ggcctgtgtc aggtgttcgc cgatgccaca 2880
cctacaggat ggggcctggc catcggacac agagccatga gaggcacctt cgtggcccct 2940
ctgcctattc acacagccga gctgctggct gcctgtttcg ccagatctag aagcggcgcc 3000
aagctgatcg gcaccgacaa ctctgtggtg ctgagccgga agtacacctc cttcccttgg 3060
ctgctgggct gcgccgccaa ctggatcctg agaggaacca gcttcgtgta cgtgccaagc 3120
gccctgaacc ctgccgccga tcctagtgct ggaaggctgg gcctgtaccg gccactgctg 3180
catctgcctt tcagacccac caccggccgg accagtctgt atgccgtgtc tcctagcgtg 3240
cccagccatc tgcccgacag agtgcatttc gccagccctc tgcatgtggc ctggcggcct 3300
ccaagaaaaa gacgggcccc tgtgaagcag accctgaatt tcgacctgct gaagctggcc 3360
ggcgacgtgg aaagcaaccc tggccctatg ggcggctggt ccagcaagcc tagacagggc 3420
atgggcacca acctgtccgt gcctaacccc ctgggattct tcccagacca ccagctggac 3480
cctgccttcg gagccaacag caacaacccc gactgggatt tcaaccctaa caaggaccac 3540
tggcccgagg ccaaccaagt gggagctggc gcatttggcc ctggcttcac acctcctcat 3600
ggcggactgc tggggtggtc acctcaggct cagggcatcc tgactacagt gcctgccgct 3660
cctcctcccg cctccaccaa tagacagagc ggcagacagc ccacccccat cagccctcca 3720
ctgagagata gccaccccca ggccatgcag tggaacagca ccacctttca ccaggccctg 3780
ctggacccaa gagtgcgcgg cctgtatttt cctgccggcg gaagctctag cggcaccgtg 3840
aatcctgtgc ctaccaccgc cagcccaatc agcagcatct tctccagaac cggcgaccct 3900
gcccccaaca tggagaacac cacctccggc tttctgggcc cactgctggt gctgcaggcc 3960
ggcttttttc tgctgacccg gatcctgacc atcccccagt ccctggactc ttggtggacc 4020
tccctgaact ttctgggagg cgcccctaca tgtcccggcc agaatagcca gagccccacc 4080
tccaatcaca gcccaaccag ctgcccccct atctgccccg gctatcggtg gatgtgcctg 4140
cggcggttca tcatctttct gttcattctg ctgctgtgtc tgatcttcct gctggtgctg 4200
ctggactacc agggcatgct gcctgtgtgc cctctgctgc ctggcacctc taccacaagc 4260
accggccctt gcaagacttg caccatccca gcccagggca ccagcatgtt ccccagctgt 4320
tgctgcacca agccctccga cggcaactgt acctgcatcc ccatcccaag cagctgggcc 4380
ttcgcccggt ttctgtggga atgggccagc gtgcggttct cctggctgag tctgctggtg 4440
cctttcgtgc agtggttcgt gggactgtcc cctaccgtgt ggctgagcgt gatctggatg 4500
atgtggtact ggggcccctc cctgtacaat atcctgtccc ccttcctgcc cctgctgccc 4560
atcttctttt gcctgtgggt gtacatctga 4590
<210> 47
<211> 4578
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 47
cccgccgcca ccatgtctct gctgtggggc ggagtgacag tgctggccgc catgctgatt 60
gctggccagg tggcctccgt ggtgttcctc gtgaagggcg gatctatggg cggctggtcc 120
agcaagccta gacagggcat gggcaccaac ctgagcgtgc ccaatcccct gggattcttc 180
ccagaccacc agctggatcc tgccttcggc gccaacagca acaaccccga ctgggacttc 240
aaccccaaca aggaccactg gcccgaggcc aaccaagtgg gagctggcgc ttttggccct 300
ggcttcacac ctcctcatgg cggactgctg ggatggtcac ctcaggccca gggcatcctg 360
acaacagtgc ctgctgctcc acctcccgcc agcaccaata gacagagcgg cagacagccc 420
acccccatca gccctccact gagagatagc cacccccagg ccatgcagtg gaacagcacc 480
acctttcacc aggccctgct ggaccctaga gtgcggggcc tgtattttcc tgccggcgga 540
agcagcagcg gcaccgtgaa tcctgtgcct accaccgcca gccccatctc cagcatcttc 600
agcagaaccg gcgaccctgc ccccaacatg gagaacacca ccagcggctt tctgggcccc 660
ctgctggtgc tgcaggccgg cttttttctg ctgacccgga tcctgaccat tccccagagc 720
ctggactcct ggtggacctc cctgaacttc ctgggcggag cccctacatg ccctggccag 780
aatagccaga gccccaccag caaccacagc cctaccagct gccctcctat ctgccccggc 840
tacaggtgga tgtgcctgcg gcggttcatc atctttctgt tcatcctgct gctgtgcctg 900
atctttctgc tggtgctgct ggactatcag ggcatgctgc ccgtgtgccc tctgctgcct 960
ggcaccagca caacaagcac cggcccttgc aagacctgca ccatccctgc ccagggaacc 1020
agcatgttcc ccagctgctg ctgcaccaag cccagcgacg gcaactgcac ctgtatcccc 1080
atcccttcca gctgggcctt cgccagattc ctgtgggagt gggccagcgt gcggttcagc 1140
tggctgtcac tgctggtgcc cttcgtgcag tggttcgtgg gcctgtctcc taccgtgtgg 1200
ctgagcgtga tctggatgat gtggtactgg ggcccctccc tgtacaatat cctgagcccc 1260
ttcctgcccc tgctgcccat cttcttttgc ctgtgggtgt acatccggaa gcggagagcc 1320
cccgtgaagc agaccctgaa tttcgacctg ctgaagctgg ccggcgacgt ggaaagcaac 1380
cctggcccta tgcagctgtt tcacctgtgt ctgatcatca gctgtagctg ccccaccgtg 1440
caggccagca agctgtgtct gggatggctg tgggggatgg acatcgaccc ctacaaagaa 1500
ttcggcgcct ctgtggaact gctgagcttc ctgcctagcg acttcttccc ctccatccgg 1560
gacctgctgg atacagccag cgccctgtat agagaggccc tggaaagccc cgagcactgc 1620
agccctcatc acaccgctct gaggcaggcc atcctgtgtt ggggcgagct gatgaacctg 1680
gccacttggg tgggaagcaa cctggaagat cccgcctccc gggaactggt ggtgtcttac 1740
gtgaacgtga acatgggcct gaagatccgg cagctgctgt ggttccacat ctcctgcctg 1800
accttcggcc gggaaaccgt gctggaatac ctggtgtcct tcggcgtgtg gatcagaacc 1860
ccccctgcct acagaccccc caacgcccct atcctgtcca ccctgcctga gacaactgtc 1920
gtgcggcgga gaggcagaag ccccagaaga agaaccccca gccccagacg cagaagaagc 1980
cagtcccctc ggcggagaag atcccagagc agggaaagcc agtgtggcgg aggatctggc 2040
ggcggaatgc ctctgagcta ccagcacttc cggaaactgc tgctgctgga tgacgaggcc 2100
ggacccctgg aagaggaact gcctagactg gccgacgagg gcctgaacag aagagtggcc 2160
gaggacctga acctgggcaa cctgaatgtg tctatcccct ggacccacaa agtgggcaac 2220
ttcaccggcc tggcctccag caccgtgccc gtgtttaatc ccgagtggca gacccccagc 2280
ttcccccaca tccatctgca ggaagatatc atcaaccgct gccagcagta cgtgggccct 2340
ctgaccgtga acgagaagcg cagactgaag ctgatcatgc ccgccaggtt ctaccccaac 2400
ctgaccaagt acctgcctct ggacaagggc atcaagccct actaccctga gcacgccgtg 2460
aaccactact tcaagacccg gcactacctg cacaccctgt ggaaggccgg catcctgtat 2520
aagcgggaaa caaccagatc cgccagcttc tgcggctccc cctacagctg ggagcaggaa 2580
ctgcagcacg gccggctggt gtttcagacc tctaccagac acggcgacga gtctttctgc 2640
agccagagca gcgggatcct gagcagatct ccagtgggcc cttgtgtgcg gtcccagctg 2700
aagcagagta gactgggcct gcagcctcag cagggctctc tggctagagg caagtctggc 2760
agaagcggca gcatccgggc cagagtgcac cctaccacca gacggtcctt tggcgtggaa 2820
cctagcggca gcggccacat cgataacagc gcctctagca cctccagctg cctgcatcag 2880
tccgccgtgc ggaaaaccgc ctacagccac ctgagcacaa gcaagagaca gagcagctcc 2940
ggccacgccg tggaactgca caatatcccc cctagcagcg ccagaagcca gagcgagggc 3000
cctatcttta gcgcctggtg gctgcagttt cggaacagca agcccgccag cgactacgcc 3060
ctgacccaca tcgtgaacct gctggaagat tggggccctg ccacagagca cggcgagcac 3120
aacatccgga tccccagaac ccctgccaga gtgacaggcg gcgtgttcct ggtggataag 3180
aaccctcaca acaccaccga gagcagactg gtggtggact tcagccagtt cagccggggc 3240
tctacccacg tgtcctggcc taagttcgcc gtgcccaacc tgcagagcct gaccaacctg 3300
ctgtccagca acctgtcctg gctgtccctg gatgtgtccg ccgccttcta ccacatccca 3360
ctgcatcccg ccgctatgcc ccatctgctc gtgggaagta gcggcctgcc tagatacgtg 3420
gccagactga gcagcacctc ccggaacatc aattaccagc acggcaccat gcaggatctg 3480
cacgacagct gcagccggaa cctgtacgtg tcccttctgc tgctgtacaa gaccttcggc 3540
agaaagctgc atctgtactc ccaccccatc atcctgggct ttagaaagat ccccatgggc 3600
gtgggactgt ccccattcct gctggcccag ttcaccagcg ccatctgttc cgtcgtgcgc 3660
agagccttcc ctcactgcct ggcctttagc tacatggacg acgtggtgct gggcgccaag 3720
agcgtgcagc acctggaatc cctgtttacc agcatcacca actttctgct gagcctgggc 3780
atccacctga accctaacaa gaccaagcgc tggggctaca gcctgaactt tatgggctac 3840
gtgatcggct cctggggcac actgcctcag gaacacatcg tgctgaaaat caagcagtgc 3900
tttcggaagc tgcctgtgaa ccggcccatc gactggaaag tgtgccagcg gattgtgggc 3960
ctgctgggct ttgccgcccc ttttacacag tgcggctacc ccgctctgat gcccctgtac 4020
gcctgcattc agagcaagca ggccttcacc ttcagcccaa cctacaaggc cttcctgtgc 4080
aagcagtacc tgaatctgta ccccgtggcc cggcagagaa gcggcctgtg tcaggtgttc 4140
gccgatgcca cacctacagg atggggcctg gccatcggac acagagccat gagaggcacc 4200
ttcgtggccc cactgcctat tcacacagcc gagctgctgg ctgcctgttt cgccaggtct 4260
agaagcggcg ccaagctgat cggcaccgac aactctgtgg tgctgagccg gaagtacacc 4320
tccttccctt ggctgctggg ctgcgccgcc aactggatcc tgagaggcac aagcttcgtg 4380
tacgtgccct ccgccctgaa tcctgccgcc gatcctagtg ctggacggct gggactgtac 4440
cggcctctgc tgcatctgcc cttcagaccc accaccggca gaaccagcct gtatgccgtg 4500
tcccctagcg tgccaagcca tctgcccgac agagtgcatt tcgcctcccc cctgcatgtg 4560
gcttggaggc ccccttaa 4578
<210> 48
<211> 4704
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 48
cccgccgcca ccatgtcttt gctttggggc ggagtgacag tgctggccgc catgcttatt 60
gctggacagg tggccagcgt ggtgttcctg gtcaaaggcg gaggacctgg cggaggcatg 120
cagctgtttc acctgtgcct gatcatcagc tgtagctgcc ctacagtgca ggccagcaag 180
ctgtgtcttg gatggctgtg gggcatggac atcgacccct acaaagaatt cggcgcctcc 240
gtggaactgc tgagcttcct gcctagcgac ttcttcccct ccatccggga tctgctggat 300
acagccagcg cactgtatag agaggccctg gaaagccccg agcactgttc tccacatcac 360
acagccctga gacaggccat cctgtgttgg ggcgagctga tgaatctggc cacatgggtc 420
ggaagcaacc tggaagatcc cgccagcaga gaactggtgg tgtcctacgt gaacgtgaac 480
atgggcctga agatccggca gctgctgtgg ttccacatct cctgcctgac cttcggcaga 540
gaaaccgtgc tggaatacct ggtgtccttc ggcgtgtgga tcagaacccc tccagcctac 600
agacctccta acgctcccat cctgagcacc ctgcctgaga caacagtcgt gcggagaaga 660
ggcagaagcc ccagaagaag aaccccatct cctcggaggc ggagatctca gtcccctcgg 720
agaagaagat cccagagcag ggaaagccag tgcggtggtg gaagtggtgg cggaatgcct 780
ctgagctacc agcacttcag aaaactgctg ctgctggacg acgaggccgg acctcttgag 840
gaagaactgc ctagactggc cgacgagggc ctgaatagaa gagtggccga ggacctgaac 900
ctgggcaacc tgaatgtgtc tatcccctgg acacacaaag tgggcaactt cacaggcctg 960
gccagctcta ccgtgcctgt gttcaatccc gagtggcaga cccctagctt ccctcacatc 1020
catctgcaag aggacatcat caaccggtgc cagcagtacg tgggccctct gaccgtgaac 1080
gagaagcgga gactgaagct gatcatgccc gccagattct accccaacct gaccaagtac 1140
ctgcctctgg acaagggcat caagccttac taccctgagc acgccgtgaa ccactacttc 1200
aagacccggc actacctgca caccctgtgg aaggccggca tcctgtacaa gagagagaca 1260
accagaagcg ccagcttctg cggcagccct tactcttggg agcaagagct gcagcacggc 1320
agactggtgt tccagacctc tacaagacac ggcgacgagt ctttctgcag ccagagcagc 1380
gggatcctgt ctagatctcc tgtgggacct tgtgtgcgga gccagctgaa acagagcaga 1440
ctgggactgc agcctcagca gggatctctg gctagaggca agtctggcag aagcggcagc 1500
atcagagcca gagtgcaccc taccaccaga cggtcctttg gcgtggaacc tagcggcagc 1560
ggccacatcg ataatagcgc cagcagcacc agcagctgtc tgcatcagtc tgctgtgcgc 1620
aagaccgcct acagccacct gagcacaagc aagagacaga gcagctctgg ccacgccgtc 1680
gagctgcaca atatccctcc aagcagcgcc agaagccaga gcgagggccc tattttttct 1740
gcctggtggc tgcagttcag aaacagcaag cccgccagcg actacgccct gacacacatc 1800
gtgaacctgc tggaagattg gggccctgcc acagaacacg gcgagcacaa catcagaatc 1860
cccaggactc ccgccagagt gaccggcgga gttttcctgg tggacaagaa ccctcacaac 1920
accaccgaga gcaggctggt ggtggacttc agccagttta gcagaggcag cacccacgtg 1980
tcctggccta aattcgccgt gcctaacctg cagagcctga ccaatctgct gagcagcaac 2040
ctgagctggc tgagcctgga tgtgtccgcc gccttctatc acatcccact gcatcctgcc 2100
gctatgcccc atctgcttgt gggaagttct ggcctgccta gatatgtggc ccggctgtcc 2160
tctaccagcc ggaacatcaa ttaccagcac gggaccatgc aggacctgca cgatagctgc 2220
tcccggaacc tgtacgttag cctgctcctg ctgtacaaaa ccttcggccg gaagctgcac 2280
ctgtactctc accctatcat cctgggcttc agaaagatcc ccatgggcgt gggactgagc 2340
ccatttctgc tggcccagtt taccagcgcc atctgcagtg ttgtgcggag agcctttcct 2400
cactgcctgg ccttcagcta catggacgat gtggtgctgg gcgccaagtc tgtgcagcac 2460
ctggaatctc tgtttacctc catcaccaac tttctgctgt ccctgggaat ccatctgaac 2520
cccaacaaga caaagagatg gggctacagc ctgaacttca tgggctacgt gatcggcagc 2580
tggggcacac tgcctcaaga gcacatcgtg ctgaagatca agcagtgctt tagaaagctg 2640
cccgtgaaca gacccatcga ctggaaagtg tgccagcgga ttgtgggcct gctgggattt 2700
gccgctcctt tcacacagtg cggctacccc gctctcatgc ctctgtacgc ctgcatccag 2760
tccaagcagg ccttcacatt cagccctacc tacaaggcct tcctgtgcaa gcagtacctg 2820
aatctgtacc ccgtggctag acagagaagc ggcctgtgtc aggtgttcgc cgatgccaca 2880
cctacaggat ggggactcgc cattggacac agggccatga gaggaacctt tgtggcccct 2940
ctgcctattc acaccgccga attgctggct gcctgtttcg ccagatctag aagcggcgcc 3000
aagctgatcg gcaccgacaa ttcagtggtg ctgagccgga agtacaccag ctttccatgg 3060
ctgctgggct gtgccgccaa ctggattctg agaggcacca gcttcgtgta cgtgcccagc 3120
gctcttaacc ctgccgctga tcctagtgct ggacggctgg gactctacag accactgctg 3180
catctgccct tcagacccac cacaggcaga accagcctgt atgccgtgtc tcctagcgtg 3240
ccaagccatc tgcctgatcg ggtgcacttt gcctctccac tgcatgtggc ttggcggcct 3300
ccaaagagcc ccaacagcaa caaccccgac tgggatttca accctaacaa ggaccactgg 3360
cctgaggcca atcaagttgg agccggcgct tttggccctg gctttacacc tcctcatggc 3420
ggactgcttg gatggtcacc tcaggctcag ggcatcctga ctacagtgcc tgctgctcca 3480
cctcctgcca gcaccaatag acagtcaggc agacagccca cacctatcag ccctccactg 3540
cgggatagtc acccacaggc catgcaatgg aacagcacca ccttccatca ggccctgctg 3600
gatcctagag tgcggggcct gtattttcct gccggcggat ctagctccgg caccgtgaat 3660
cctgtgccta caaccgcctc tcctatcagc agcatcttca gccggacagg cgaccctgct 3720
cctaatggct ctaagggcaa gagaaagcgg agggcccctg tgaaacagac cctgaatttc 3780
gacctgctga agctggccgg cgacgtggaa tctaaccctg gacctatggg cggctggtcc 3840
agcaaaccta gacaaggcat gggcaccaat ctgagcgtgc ccaatccact gggattcttc 3900
ccagaccacc agctggaccc tgccttcggc gccaatagca acaatcctga ttgggacttt 3960
aatcccaaca aagatcattg gcccgaagct aatcaagtcg gcctggaagg cggaagcggc 4020
ggcatggaga ataccacatc tggctttctg ggcccactgc tggttctcca ggccggcttt 4080
tttctcctga cacggatcct gacaatccct cagagcctgg actcttggtg gacctctctg 4140
aacttccttg gcggagcccc tacctgtcct ggacagaata gccagtctcc taccagcaat 4200
cacagcccca caagctgccc tccaatctgc cctggctatc ggtggatgtg cctgcggcgg 4260
ttcatcatct ttctgttcat cctgctgctg tgtctgatct tcctgctggt cctcctggac 4320
taccagggca tgctgccagt ttgtcctctg ctgcctggca cctccacaac atctacaggc 4380
ccttgcaaga cctgtacaat ccccgctcag ggaaccagca tgttccccag ctgttgctgc 4440
accaagccaa gcgacggcaa ctgcacatgc atccccattc ctagcagctg ggcctttgcc 4500
agatttctgt gggagtgggc ctccgtgcgg tttagctggc tgtctctgct cgtgcctttc 4560
gtgcagtggt tcgtcggact gtctccaacc gtgtggctga gcgtgatctg gatgatgtgg 4620
tactggggcc ctagcctgta caatattctg agccccttcc tgcctctcct gccaatcttc 4680
ttttgtctgt gggtgtacat ctga 4704
<210> 49
<211> 4800
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 49
cccgccgcca ccatgtcttt gctttggggc ggagtgacag tgctggccgc catgcttatt 60
gctggacagg tggccagcgt ggtgttcctg gtcaaaggcg gaggacctgg cggaggcatg 120
cagctgtttc acctgtgcct gatcatcagc tgtagctgcc ctacagtgca ggccagcaag 180
ctgtgtcttg gatggctgtg gggcatggac atcgacccct acaaagaatt cggcgcctcc 240
gtggaactgc tgagcttcct gcctagcgac ttcttcccct ccatccggga tctgctggat 300
acagccagcg cactgtatag agaggccctg gaaagccccg agcactgttc tccacatcac 360
acagccctga gacaggccat cctgtgttgg ggcgagctga tgaatctggc cacatgggtc 420
ggaagcaacc tggaagatcc cgccagcaga gaactggtgg tgtcctacgt gaacgtgaac 480
atgggcctga agatccggca gctgctgtgg ttccacatct cctgcctgac cttcggcaga 540
gaaaccgtgc tggaatacct ggtgtccttc ggcgtgtgga tcagaacccc tccagcctac 600
agacctccta acgctcccat cctgagcacc ctgcctgaga caacagtcgt gcggagaaga 660
ggcagaagcc ccagaagaag aaccccatct cctcggaggc ggagatctca gtcccctcgg 720
agaagaagat cccagagcag ggaaagccag tgcggtggtg gaagtggtgg cggaatgcct 780
ctgagctacc agcacttcag aaaactgctg ctgctggacg acgaggccgg acctcttgag 840
gaagaactgc ctagactggc cgacgagggc ctgaatagaa gagtggccga ggacctgaac 900
ctgggcaacc tgaatgtgtc tatcccctgg acacacaaag tgggcaactt cacaggcctg 960
gccagctcta ccgtgcctgt gttcaatccc gagtggcaga cccctagctt ccctcacatc 1020
catctgcaag aggacatcat caaccggtgc cagcagtacg tgggccctct gaccgtgaac 1080
gagaagcgga gactgaagct gatcatgccc gccagattct accccaacct gaccaagtac 1140
ctgcctctgg acaagggcat caagccttac taccctgagc acgccgtgaa ccactacttc 1200
aagacccggc actacctgca caccctgtgg aaggccggca tcctgtacaa gagagagaca 1260
accagaagcg ccagcttctg cggcagccct tactcttggg agcaagagct gcagcacggc 1320
agactggtgt tccagacctc tacaagacac ggcgacgagt ctttctgcag ccagagcagc 1380
gggatcctgt ctagatctcc tgtgggacct tgtgtgcgga gccagctgaa acagagcaga 1440
ctgggactgc agcctcagca gggatctctg gctagaggca agtctggcag aagcggcagc 1500
atcagagcca gagtgcaccc taccaccaga cggtcctttg gcgtggaacc tagcggcagc 1560
ggccacatcg ataatagcgc cagcagcacc agcagctgtc tgcatcagtc tgctgtgcgc 1620
aagaccgcct acagccacct gagcacaagc aagagacaga gcagctctgg ccacgccgtc 1680
gagctgcaca atatccctcc aagcagcgcc agaagccaga gcgagggccc tattttttct 1740
gcctggtggc tgcagttcag aaacagcaag cccgccagcg actacgccct gacacacatc 1800
gtgaacctgc tggaagattg gggccctgcc acagaacacg gcgagcacaa catcagaatc 1860
cccaggactc ccgccagagt gaccggcgga gttttcctgg tggacaagaa ccctcacaac 1920
accaccgaga gcaggctggt ggtggacttc agccagttta gcagaggcag cacccacgtg 1980
tcctggccta aattcgccgt gcctaacctg cagagcctga ccaatctgct gagcagcaac 2040
ctgagctggc tgagcctgga tgtgtccgcc gccttctatc acatcccact gcatcctgcc 2100
gctatgcccc atctgcttgt gggaagttct ggcctgccta gatatgtggc ccggctgtcc 2160
tctaccagcc ggaacatcaa ttaccagcac gggaccatgc aggacctgca cgatagctgc 2220
tcccggaacc tgtacgttag cctgctcctg ctgtacaaaa ccttcggccg gaagctgcac 2280
ctgtactctc accctatcat cctgggcttc agaaagatcc ccatgggcgt gggactgagc 2340
ccatttctgc tggcccagtt taccagcgcc atctgcagtg ttgtgcggag agcctttcct 2400
cactgcctgg ccttcagcta catggacgat gtggtgctgg gcgccaagtc tgtgcagcac 2460
ctggaatctc tgtttacctc catcaccaac tttctgctgt ccctgggaat ccatctgaac 2520
cccaacaaga caaagagatg gggctacagc ctgaacttca tgggctacgt gatcggcagc 2580
tggggcacac tgcctcaaga gcacatcgtg ctgaagatca agcagtgctt tagaaagctg 2640
cccgtgaaca gacccatcga ctggaaagtg tgccagcgga ttgtgggcct gctgggattt 2700
gccgctcctt tcacacagtg cggctacccc gctctcatgc ctctgtacgc ctgcatccag 2760
tccaagcagg ccttcacatt cagccctacc tacaaggcct tcctgtgcaa gcagtacctg 2820
aatctgtacc ccgtggctag acagagaagc ggcctgtgtc aggtgttcgc cgatgccaca 2880
cctacaggat ggggactcgc cattggacac agggccatga gaggaacctt tgtggcccct 2940
ctgcctattc acaccgccga attgctggct gcctgtttcg ccagatctag aagcggcgcc 3000
aagctgatcg gcaccgacaa ttcagtggtg ctgagccgga agtacaccag ctttccatgg 3060
ctgctgggct gtgccgccaa ctggattctg agaggcacca gcttcgtgta cgtgcccagc 3120
gctcttaacc ctgccgctga tcctagtgct ggacggctgg gactctacag accactgctg 3180
catctgccct tcagacccac cacaggcaga accagcctgt atgccgtgtc tcctagcgtg 3240
ccaagccatc tgcctgatcg ggtgcacttt gcctctccac tgcatgtggc ttggcggcct 3300
ccaaagagcc ccaacagcaa caaccccgac tgggatttca accctaacaa ggaccactgg 3360
cctgaggcca atcaagttgg agccggcgct tttggccctg gctttacacc tcctcatggc 3420
ggactgcttg gatggtcacc tcaggctcag ggcatcctga ctacagtgcc tgctgctcca 3480
cctcctgcca gcaccaatag acagtcaggc agacagccca cacctatcag ccctccactg 3540
cgggatagtc acccacaggc catgcaatgg aacagcacca ccttccatca ggccctgctg 3600
gatcctagag tgcggggcct gtattttcct gccggcggat ctagctccgg caccgtgaat 3660
cctgtgccta caaccgcctc tcctatcagc agcatcttca gccggacagg cgaccctgct 3720
cctaatggct ctaagggcaa gagaaagcgg agggcccctg tgaaacagac cctgaatttc 3780
gacctgctga agctggccgg cgacgtggaa tctaaccccg gacctatgga cgccatgaag 3840
aggggcctgt gttgtgtcct gctgctgtgt ggcgctgtgt tcgtgtctcc cagccaagag 3900
atccacgcca gatttcggag aatgggcggc tggtccagca agcctagaca aggcatgggc 3960
accaatctga gcgtgcccaa tccactggga ttcttcccag accaccagct ggaccctgcc 4020
ttcggcgcca atagcaacaa tcctgattgg gactttaatc ccaacaaaga tcattggccc 4080
gaagctaatc aagtcggcct ggaaggcgga agcggcggca tggagaatac cacatctggc 4140
tttctgggcc cactgctggt tctccaggcc ggcttttttc tcctgacacg gatcctgaca 4200
atccctcaga gcctggacag ttggtggacc tctctgaact tccttggcgg agcccctacc 4260
tgtcctggac agaatagcca gtctcctacc agcaatcaca gccccacaag ctgccctcca 4320
atctgccctg gctatcggtg gatgtgcctg cggcggttca tcatctttct gttcattctg 4380
ctgctttgcc tgatcttcct gctggtcctc ctggactacc agggcatgct gccagtttgt 4440
cctctgctgc ctggcacctc cacaacctct acaggccctt gcaagacctg tacaatcccc 4500
gctcagggaa ccagcatgtt ccccagctgt tgctgcacca agccaagcga cggcaactgc 4560
acatgcatcc ccattcctag cagctgggcc tttgccagat tcctctggga atgggcctcc 4620
gtgcggttta gctggctgtc tctgctcgtg cctttcgtgc agtggttcgt cggactgtct 4680
ccaaccgtgt ggctgagcgt gatctggatg atgtggtact ggggccctag cctgtacaat 4740
attctgagcc ccttcctgcc tctcctgcca atcttctttt gtctgtgggt gtacatctga 4800
<210> 50
<211> 2100
<212> DNA
<213> 人工序列
<220>
<223> 启动子
<400> 50
tgagatttct gtcgccgact aaattcatgt cgcgcgatag tggtgtttat cgccgataga 60
gatggcgata ttggaaaaat cgatatttga aaatatggca tattgaaaat gtcgccgatg 120
tgagtttctg tgtaactgat atcgccattt ttccaaaagt gatttttggg catacgcgat 180
atctggcgat agcgcttata tcgtttacgg gggatggcga tagacgactt tggtgacttg 240
ggcgattctg tgtgtcgcaa atatcgcagt ttcgatatag gtgacagacg atatgaggct 300
atatcgccga tagaggcgac atcaagctgg cacatggcca atgcatatcg atctatacat 360
tgaatcaata ttggccatta gccatattat tcattggtta tatagcataa atcaatattg 420
gctattggcc attgcatacg ttgtatccat atcataatat gtacatttat attggctcat 480
gtccaacatt accgccatgt tgacattgat tattgactag ttattaatag taatcaatta 540
cggggtcatt agttcatagc ccatatatgg agttccgcgt tacataactt acggtaaatg 600
gcccgcctgg ctgaccgccc aacgaccccc gcccattgac gtcaataatg acgtatgttc 660
ccatagtaac gccaataggg actttccatt gacgtcaatg ggtggagtat ttacggtaaa 720
ctgcccactt ggcagtacat caagtgtatc atatgccaag tacgccccct attgacgtca 780
atgacggtaa atggcccgcc tggcattatg cccagtacat gaccttatgg gactttccta 840
cttggcagta catctacgta ttagtcatcg ctattaccat ggtgatgcgg ttttggcagt 900
acatcaatgg gcgtggatag cggtttgact cacggggatt tccaagtctc caccccattg 960
acgtcaatgg gagtttgttt tggcaccaaa atcaacggga ctttccaaaa tgtcgtaaca 1020
actccgcccc attgacgcaa atgggcggta ggcgtgtacg gtgggaggtc tatataagca 1080
gagctctccc tatcagtgat agagatctcc ctatcagtga tagagatcgt cgacgagctc 1140
gtttagtgaa ccgtcagatc gcctggagac gccatccacg ctgttttgac ctccatagaa 1200
gacaccggga ccgatccagc ctccgcggcc gggaacggtg cattggaacg cggattcccc 1260
gtgccaagag tgacgtaagt accgcctata gagtctatag gcccaccccc ttggcttctt 1320
atgcatgcta tactgttttt ggcttggggt ctatacaccc ccgcttcctc atgttatagg 1380
tgatggtata gcttagccta taggtgtggg ttattgacca ttattgacca ctcccctatt 1440
ggtgacgata ctttccatta ctaatccata acatggctct ttgccacaac tctctttatt 1500
ggctatatgc caatacactg tccttcagag actgacacgg actctgtatt tttacaggat 1560
ggggtctcat ttattattta caaattcaca tatacaacac caccgtcccc agtgcccgca 1620
gtttttatta aacataacgt gggatctcca cgcgaatctc gggtacgtgt tccggacatg 1680
ggctcttctc cggtagcggc ggagcttcta catccgagcc ctgctcccat gcctccagcg 1740
actcatggtc gctcggcagc tccttgctcc taacagtgga ggccagactt aggcacagca 1800
cgatgcccac caccaccagt gtgccgcaca aggccgtggc ggtagggtat gtgtctgaaa 1860
atgagctcgg ggagcgggct tgcaccgctg acgcatttgg aagacttaag gcagcggcag 1920
aagaagatgc aggcagctga gttgttgtgt tctgataaga gtcagaggta actcccgttg 1980
cggtgctgtt aacggtggag ggcagtgtag tctgagcagt actcgttgct gccgcgcgcg 2040
ccaccagaca taatagctga cagactaaca gactgttcct ttccatgggt cttttctgca 2100
<210> 51
<211> 673
<212> DNA
<213> 人工序列
<220>
<223> 启动子
<400> 51
cctttcactc attagatgca tgtcgttaca taacttacgg taaatggccc gcctggctga 60
ccgcccaacg acccccgccc attgacgtca ataatgacgt atgttcccat agtaacgcca 120
atagggactt tccattgacg tcaatgggtg gagtatttac ggtaaactgc ccacttggca 180
gtacatcaag tgtatcatat gccaagtacg ccccctattg acgtcaatga cggtaaatgg 240
cccgcctggc attatgccca gtacatgacc ttatgggact ttcctacttg gcagtacatc 300
tacgtattag tcatcgctat taccatggtg atgcggtttt ggcagtacat caatgggcgt 360
ggatagcggt ttgactcacg gggatttcca agtctccacc ccattgacgt caatgggagt 420
ttgttttgga accaaaatca acgggacttt ccaaaatgtc gtaacaactc cgccccattg 480
acgcaaatgg gcggtaggcg tgtacggtgg gaggtctata taagcagagc tctccctatc 540
agtgatagag atctccctat cagtgataga gatcgtcgac gagctcgttt agtgaaccgt 600
cagatcgcct ggagacgcca tccacgctgt tttgacctcc atagaagaca ccgggaccga 660
tccagcctcc ggt 673
<210> 52
<211> 119
<212> PRT
<213> 乙型肝炎病毒
<400> 52
Met Gly Gly Trp Ser Ser Lys Pro Arg Gln Gly Met Gly Thr Asn Leu
1 5 10 15
Ser Val Pro Asn Pro Leu Gly Phe Phe Pro Asp His Gln Leu Asp Pro
20 25 30
Ala Phe Gly Ala Asn Ser Asn Asn Pro Asp Trp Asp Phe Asn Pro Asn
35 40 45
Lys Asp His Trp Pro Glu Ala Asn Gln Val Gly Ala Gly Ala Phe Gly
50 55 60
Pro Gly Phe Thr Pro Pro His Gly Gly Leu Leu Gly Trp Ser Pro Gln
65 70 75 80
Ala Gln Gly Ile Leu Thr Thr Val Pro Ala Ala Pro Pro Pro Ala Ser
85 90 95
Thr Asn Arg Gln Ser Gly Arg Gln Pro Thr Pro Ile Ser Pro Pro Leu
100 105 110
Arg Asp Ser His Pro Gln Ala
115
<210> 53
<211> 55
<212> PRT
<213> 乙型肝炎病毒
<400> 53
Met Gln Trp Asn Ser Thr Thr Phe His Gln Ala Leu Leu Asp Pro Arg
1 5 10 15
Val Arg Gly Leu Tyr Phe Pro Ala Gly Gly Ser Ser Ser Gly Thr Val
20 25 30
Asn Pro Val Pro Thr Thr Ala Ser Pro Ile Ser Ser Ile Phe Ser Arg
35 40 45
Thr Gly Asp Pro Ala Pro Asn
50 55
<210> 54
<211> 25
<212> PRT
<213> 乙型肝炎病毒
<400> 54
Phe Leu Gly Pro Leu Leu Val Leu Gln Ala Gly Phe Phe Leu Leu Thr
1 5 10 15
Arg Ile Leu Thr Ile Pro Gln Ser Leu
20 25
<210> 55
<211> 19
<212> PRT
<213> 乙型肝炎病毒
<400> 55
Phe Ile Ile Phe Leu Phe Ile Leu Leu Leu Cys Leu Ile Phe Leu Leu
1 5 10 15
Val Leu Leu
<210> 56
<211> 25
<212> PRT
<213> 乙型肝炎病毒
<400> 56
Arg Phe Leu Trp Glu Trp Ala Ser Val Arg Phe Ser Trp Leu Ser Leu
1 5 10 15
Leu Val Pro Phe Val Gln Trp Phe Val
20 25
<210> 57
<211> 22
<212> PRT
<213> 乙型肝炎病毒
<400> 57
Thr Val Trp Leu Ser Val Ile Trp Met Met Trp Tyr Trp Gly Pro Ser
1 5 10 15
Leu Tyr Asn Ile Leu Ser
20
<210> 58
<211> 7239
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 58
gtaatctatt cgatataccg ttgctaacag tatactggcc caataactgt ggatggaaaa 60
tctataataa tacattaata tcatccgatg gtgctagggt tatttggatg gatgcgtata 120
aattttcttg cggtttatct ttacaagact attgttatca ttggggtagc aaaccagaga 180
gccgaccatt cgatttaata aaaaaatcag atgctaaacg caattctaaa tcgttggtca 240
aagaatctat ggcatccttg aaatccttgt acgaggcatt cgagacacaa tcaggagcgt 300
tagaagtttt aatgagtcca tgtaggatgt tttcgttttc tagaatagaa gacatgttct 360
taactagtgt cattaataga gtatccgaga atactggaat ggggatgtat tatcctacca 420
acgatatacc ttctctattt atcgaatcat ctatctgtct agattatatt atagtaaata 480
atcaggaatc caacaaatat cgtatcaaat ctgttctcga tatcatttct tcaaaacaat 540
accctgcagg acgtcccaac tacgttaaaa atggtacaaa aggaaagtta tatatcgcgt 600
tgtgtaaagt taccgtacct actaacgacc atattccagt agtttatcac gatgatgaca 660
atactaccac ctttattaca gtattgacgt ccgtcgatat tgaaactgct atcagagcag 720
gatattcgat agtcgaatta ggggctttac aatgggataa taatattcca gaacttaaaa 780
acggtttact ggatagtatc aagatgattt atgacttgaa cgcagttaca acaaataatt 840
tattggaaca gctcatagaa aatattaact ttaacaactc tagtataatt tcgttgtttt 900
atacatttgc cattagttat tgccgagcat tcatttactc aattatggaa accatagatc 960
cggtgtatat atctcagttc agttataaag aattatacgt tagtagctct tataaagata 1020
ttaatgaatc catgagtcag atggtaaaat tataaaaagt gaaaaacaat attattttta 1080
tcgttggttg ttacactatg tcacttcttt ggggcggagt tacagttctt gctgctatgc 1140
ttattgctgg acaagttgct tctgttgtgt ttcttgtttc taaatctgga cctccttctg 1200
gaaaatctaa ttctaacaat cctgattggg atttcaatcc taacaaagat cattggcctg 1260
aagctaatca agttggagct ggtgcttttg gacctggttt tacacctcct catggtggat 1320
tgcttggatg gtcacctcaa gctcagggaa ttcttacaac agttccagct gctcctcctc 1380
ctgcttctac aaatagacaa tctggtagac aacctacacc tatttctcca cctcttagag 1440
attctcatcc tcaagctatg caatggaatt ctactacatt tcatcaagct ttgcttgatc 1500
ctagagttag aggactttat tttcctgctg gtggaagttc ttctggaaca gttaatcctg 1560
ttcctacaac agcttctcca atttcttcta tattttctag aacaggcgat cctgctccta 1620
atggatcaaa atctggatca aaaatgcctc tgtcttatca acactttaga aaattgctgc 1680
ttcttgatga tgaagctgga cctcttgaag aagaattgcc tagacttgct gatgaaggac 1740
ttaatagaag agttgctgaa gatcttaatc tgggaaatct taatgtttct attccttgga 1800
cacacaaagt tggaaatttc acaggacttg catcttctac agtgcctgtt tttaatcctg 1860
aatggcaaac accttctttt ccacatattc atctgcaaga ggatatcatc aatagatgtc 1920
aacaatatgt tggaccactg acagttaatg agaagagaag gcttaaactt attatgcctg 1980
ctagattcta tcctaatctt acaaagtatt tgcctctgga taagggaatc aaaccttatt 2040
atcctgaaca tgctgtgaat cactacttta aaacaagaca ttatctgcat acactgtgga 2100
aagctggtat tctttacaaa agagaaacaa caagatctgc ttcattttgt ggatctccat 2160
attcttggga acaagaactt caacatggta gacttgtttt tcaaacatct acaagacatg 2220
gggatgaatc attttgttct caaagttctg gaattctttc tagatctcct gttggacctt 2280
gtgttagatc tcaacttaaa caatctagac ttggacttca acctcaacaa ggatctcttg 2340
ctagaggaaa aagtggaaga tctggatcta ttagagctag agttcatcct acaactagaa 2400
gatcttttgg agttgaacct tctggatctg gacatattga taattctgcc tcttctacat 2460
cttcttgtct gcatcaatct gctgttagaa agacagctta ttctcatttg tctacttcta 2520
agagacaatc atcttctgga catgctgttg aacttcataa tattcctcca agtagtgcta 2580
gaagtcaatc tgaaggacca atattttcag cttggtggct tcaattcaga aattctaaac 2640
ctgcttctga ttatgctctg acacatatag ttaatttgct tgaagattgg ggacctgcta 2700
cagaacatgg cgaacacaat attagaatac ctagaactcc tgctagagtt acaggcggag 2760
tctttttggt tgataagaat cctcataata ccacagaatc aagacttgtt gttgattttt 2820
cacagttttc tagaggatct acacatgttt cttggcctaa atttgctgtt ccaaatcttc 2880
aatctcttac aaatttgctt tcatctaatc tttcttggct gtctcttgat gtttctgctg 2940
ccttttatca tattcctctt catcctgctg caatgcctca tttgcttgtt ggatcatctg 3000
gacttccaag atatgttgct agacttagct ctacatctag aaatatcaat tatcagcatg 3060
gaacaatgca ggatcttcac gattcttgta gtaggaatct gtatgtttct ttgcttctgc 3120
tgtataagac atttggaaga aaacttcatc tgtattctca ccctattatt ctgggtttta 3180
gaaagattcc tatgggagtt ggactttctc cttttttgct tgctcaattc acatctgcta 3240
tttgttctgt tgttagaagg gcttttcctc attgtcttgc attttcttat atggatgatg 3300
ttgttcttgg agctaaatct gttcaacatc ttgaaagtct gtttacctct attactaatt 3360
ttctgctttc tctgggaatt catctgaatc caaacaaaac aaagagatgg ggatattctc 3420
ttaatttcat gggatatgtt attggatctt ggggaacact tcctcaagaa catatcgttt 3480
tgaaaatcaa gcaatgtttc agaaaactgc ctgtgaatag acctattgat tggaaagttt 3540
gtcaaagaat tgtgggactt cttggatttg ctgctccttt tacacaatgt ggatatcctg 3600
ctcttatgcc actttatgct tgtattcaat ctaaacaggc ttttacattt tctccaacat 3660
acaaagcttt tctgtgtaaa cagtatctga atctttatcc tgtggctaga caaagatctg 3720
gtctttgtca agtttttgct gatgctacac caacaggatg gggacttgct attggacata 3780
gagctatgag aggaacattt gttgctccat tgcctattca tacagctgaa ttgcttgctg 3840
cttgttttgc tagatctaga agcggagcaa aacttattgg tacagataat agtgttgtcc 3900
tgagtagaaa gtacacatct tttccatggt tgttgggatg tgctgctaat tggattctta 3960
gaggaacttc ttttgtttat gttccttctg ctcttaatcc tgcagctgat ccatctgctg 4020
gtagattggg actgtataga ccacttcttc atttgccttt tagaccaaca actggaagaa 4080
catctcttta tgctgtttct ccttctgttc catctcattt gcctgataga gttcattttg 4140
cttctccact tcatgttgct tggaggccac catctaaatc tccaggttct ggaccaccta 4200
tgcaactttt tcatttgtgt ttgatcatta gctgttcttg tcctacagtt caagcttcta 4260
aactttgtct tggatggctt tggggaatgg atattgatcc atacaaagaa tttggagcta 4320
gtgttgaatt gctgtcattt cttccatctg attttttccc ttctattcgt gatcttcttg 4380
atacagcatc tgctctgtat agagaagctc ttgaatctcc tgaacactgt tctccacatc 4440
atacagcact tagacaagct attctttgtt ggggagaact tatgaatctt gctacatggg 4500
ttggatctaa tttggaagat ccagcttcta gagaattggt ggtttcttat gttaatgtga 4560
atatgggact gaaaattaga caactgcttt ggtttcatat ctcttgtctt acatttggta 4620
gagaaacagt tttggaatat ttggtttctt ttggcgtttg gattagaaca cctccagctt 4680
atagacctcc taatgctcct attttgtcta cacttcctga aacaacagtc gttagaagaa 4740
gaggaagatc tccaagaaga agaacaccaa gtcctagaag aagaagatct caatcaccaa 4800
gaagaagaag aagtcaatct agagaatctc aatgttgatt tttgttcgac attaaaaatt 4860
gaaaataaat acaaaggttc ttgagggttg tgttaaattg aaagcgagaa ataatcataa 4920
atatgattca ggtgacggat ccatggatgc tatgaagcga ggactttgtt gtgttttgct 4980
tctttgtggt gctgtgtttg tttctccatc tcaagaaatt catgccagat tcagaagaat 5040
gggaggctgg tcatctaaac ctagacaagg catgggaaca aatctttctg ttcctaatcc 5100
tttgggattc tttcctgatc atcaattgga tccagcattt ggagcaaata gtaacaatcc 5160
agattgggac tttaacccaa acaaagatca ttggccagaa gctaatcaag ttggagcatc 5220
taaaggtgga aaaagtggaa tggaaaacac tacatctgga tttcttggac ctttgcttgt 5280
tcttcaagct ggatttttcc tgttgacaag aatacttaca attcctcaat cactggattc 5340
ttggtggaca agtcttaatt ttcttggagg tgctcctaca tgtcctggac aaaattctca 5400
atctccaact tctaatcatt ctcctacatc ttgtcctcca atttgtcctg gatatagatg 5460
gatgtgtctt agaagattca ttatctttct tttcatactg ctgctgtgtc tgattttcct 5520
tcttgttttg ttggattatc agggaatgct tcctgtttgt cctttgcttc ctggaacttc 5580
tacaacaagt acaggacctt gtaaaacatg tacaattcca gcacagggaa catctatgtt 5640
tccaagttgt tgttgtacaa aaccttctga tggaaattgc acatgtattc ctattccaag 5700
ttcttgggca tttgctagat ttctttggga atgggcttct gttagattca gttggttgtc 5760
tcttttggtt ccatttgttc agtggtttgt tggattgtct cctacagttt ggctttctgt 5820
tatttggatg atgtggtatt ggggaccttc tctttacaat attttgagtc cttttctccc 5880
tttgctgcca attttctttt gtctttgggt ttacatttga ttaaccgagt ttctgcatta 5940
ttgtaattcg tatgctggca ccatcaaaga atcacttcta aaagatatca atatcacaca 6000
tacaaatatt actaccctat tgaatgagac agccaaggtt atcaagttag taaaatctct 6060
ggtagataaa gaagatactg atattgtgaa taatttcatt accaaagaaa ttaaaaacag 6120
agacaaaata gttaatagtt tgtctctatc aaacctggac tttcgtttgt aaattggggc 6180
tttttgtaca ataaatgggt gttgccaatg attcatcccc tgaatatcaa tggatgtctc 6240
cccatagatt atcagatact gttatattag gagactgttt gtattttaac aatataatgt 6300
cccaattaga tttacaccaa aattgggctc catcagttag attgttaaat tattttaaga 6360
attttaataa ggaaacacta ctaaagatag aagagaatga ttacattaat tcatcctttt 6420
tccaacaaaa ggataaacga ttttatccta taaacgacga tttttatcac atatctacag 6480
gaggatatgg tatagtcttt aagatagata actatgtagt aaaatttgta ttcgaggcca 6540
caaaattata tagtcccatg gaaactacgg cggagttcac agtacccaaa tttctataca 6600
acaatctaaa gggagatgaa aaaaaattaa tcgtgtgtgc gtgggccatg ggattaaact 6660
ataaattaac atttttacat actctgtata aacgtgttct tcatatgttg ctattattga 6720
tacaaactat ggatggtcag gaactatcat tgagatattc ttctaaagtt tttttaaagg 6780
cgtttaacga gagaaaggac agtatcaaat tcgtgaaatt actatcccac ttttatccgg 6840
cagttattaa cagtaatatt aatgttataa actattttaa ccgcatgttt cactttttcg 6900
aacatgaaaa gagaactaac tacgaatacg aaagaggaaa tattataatt tttcccctag 6960
cactgtattc ggcagataaa gtagataccg agctagctat caaattagga tttaaatctt 7020
tggtacaata cataaagttt atctttttac agatggctct gttatacatt aaaatttacg 7080
aactaccatg ctgcgacaac tttttacacg cagatcttaa acccgataat atcttacttt 7140
ttgattccaa tgaaccaata ataattcatc taaaggataa aaagtttgtt tttaatgaac 7200
gtattaaatc ggcattaaac gactttgact tttcccaag 7239
<210> 59
<211> 3741
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 59
atgtcacttc tttggggcgg agttacagtt cttgctgcta tgcttattgc tggacaagtt 60
gcttctgttg tgtttcttgt ttctaaatct ggacctcctt ctggaaaatc taattctaac 120
aatcctgatt gggatttcaa tcctaacaaa gatcattggc ctgaagctaa tcaagttgga 180
gctggtgctt ttggacctgg ttttacacct cctcatggtg gattgcttgg atggtcacct 240
caagctcagg gaattcttac aacagttcca gctgctcctc ctcctgcttc tacaaataga 300
caatctggta gacaacctac acctatttct ccacctctta gagattctca tcctcaagct 360
atgcaatgga attctactac atttcatcaa gctttgcttg atcctagagt tagaggactt 420
tattttcctg ctggtggaag ttcttctgga acagttaatc ctgttcctac aacagcttct 480
ccaatttctt ctatattttc tagaacaggc gatcctgctc ctaatggatc aaaatctgga 540
tcaaaaatgc ctctgtctta tcaacacttt agaaaattgc tgcttcttga tgatgaagct 600
ggacctcttg aagaagaatt gcctagactt gctgatgaag gacttaatag aagagttgct 660
gaagatctta atctgggaaa tcttaatgtt tctattcctt ggacacacaa agttggaaat 720
ttcacaggac ttgcatcttc tacagtgcct gtttttaatc ctgaatggca aacaccttct 780
tttccacata ttcatctgca agaggatatc atcaatagat gtcaacaata tgttggacca 840
ctgacagtta atgagaagag aaggcttaaa cttattatgc ctgctagatt ctatcctaat 900
cttacaaagt atttgcctct ggataaggga atcaaacctt attatcctga acatgctgtg 960
aatcactact ttaaaacaag acattatctg catacactgt ggaaagctgg tattctttac 1020
aaaagagaaa caacaagatc tgcttcattt tgtggatctc catattcttg ggaacaagaa 1080
cttcaacatg gtagacttgt ttttcaaaca tctacaagac atggggatga atcattttgt 1140
tctcaaagtt ctggaattct ttctagatct cctgttggac cttgtgttag atctcaactt 1200
aaacaatcta gacttggact tcaacctcaa caaggatctc ttgctagagg aaaaagtgga 1260
agatctggat ctattagagc tagagttcat cctacaacta gaagatcttt tggagttgaa 1320
ccttctggat ctggacatat tgataattct gcctcttcta catcttcttg tctgcatcaa 1380
tctgctgtta gaaagacagc ttattctcat ttgtctactt ctaagagaca atcatcttct 1440
ggacatgctg ttgaacttca taatattcct ccaagtagtg ctagaagtca atctgaagga 1500
ccaatatttt cagcttggtg gcttcaattc agaaattcta aacctgcttc tgattatgct 1560
ctgacacata tagttaattt gcttgaagat tggggacctg ctacagaaca tggcgaacac 1620
aatattagaa tacctagaac tcctgctaga gttacaggcg gagtcttttt ggttgataag 1680
aatcctcata ataccacaga atcaagactt gttgttgatt tttcacagtt ttctagagga 1740
tctacacatg tttcttggcc taaatttgct gttccaaatc ttcaatctct tacaaatttg 1800
ctttcatcta atctttcttg gctgtctctt gatgtttctg ctgcctttta tcatattcct 1860
cttcatcctg ctgcaatgcc tcatttgctt gttggatcat ctggacttcc aagatatgtt 1920
gctagactta gctctacatc tagaaatatc aattatcagc atggaacaat gcaggatctt 1980
cacgattctt gtagtaggaa tctgtatgtt tctttgcttc tgctgtataa gacatttgga 2040
agaaaacttc atctgtattc tcaccctatt attctgggtt ttagaaagat tcctatggga 2100
gttggacttt ctcctttttt gcttgctcaa ttcacatctg ctatttgttc tgttgttaga 2160
agggcttttc ctcattgtct tgcattttct tatatggatg atgttgttct tggagctaaa 2220
tctgttcaac atcttgaaag tctgtttacc tctattacta attttctgct ttctctggga 2280
attcatctga atccaaacaa aacaaagaga tggggatatt ctcttaattt catgggatat 2340
gttattggat cttggggaac acttcctcaa gaacatatcg ttttgaaaat caagcaatgt 2400
ttcagaaaac tgcctgtgaa tagacctatt gattggaaag tttgtcaaag aattgtggga 2460
cttcttggat ttgctgctcc ttttacacaa tgtggatatc ctgctcttat gccactttat 2520
gcttgtattc aatctaaaca ggcttttaca ttttctccaa catacaaagc ttttctgtgt 2580
aaacagtatc tgaatcttta tcctgtggct agacaaagat ctggtctttg tcaagttttt 2640
gctgatgcta caccaacagg atggggactt gctattggac atagagctat gagaggaaca 2700
tttgttgctc cattgcctat tcatacagct gaattgcttg ctgcttgttt tgctagatct 2760
agaagcggag caaaacttat tggtacagat aatagtgttg tcctgagtag aaagtacaca 2820
tcttttccat ggttgttggg atgtgctgct aattggattc ttagaggaac ttcttttgtt 2880
tatgttcctt ctgctcttaa tcctgcagct gatccatctg ctggtagatt gggactgtat 2940
agaccacttc ttcatttgcc ttttagacca acaactggaa gaacatctct ttatgctgtt 3000
tctccttctg ttccatctca tttgcctgat agagttcatt ttgcttctcc acttcatgtt 3060
gcttggaggc caccatctaa atctccaggt tctggaccac ctatgcaact ttttcatttg 3120
tgtttgatca ttagctgttc ttgtcctaca gttcaagctt ctaaactttg tcttggatgg 3180
ctttggggaa tggatattga tccatacaaa gaatttggag ctagtgttga attgctgtca 3240
tttcttccat ctgatttttt cccttctatt cgtgatcttc ttgatacagc atctgctctg 3300
tatagagaag ctcttgaatc tcctgaacac tgttctccac atcatacagc acttagacaa 3360
gctattcttt gttggggaga acttatgaat cttgctacat gggttggatc taatttggaa 3420
gatccagctt ctagagaatt ggtggtttct tatgttaatg tgaatatggg actgaaaatt 3480
agacaactgc tttggtttca tatctcttgt cttacatttg gtagagaaac agttttggaa 3540
tatttggttt cttttggcgt ttggattaga acacctccag cttatagacc tcctaatgct 3600
cctattttgt ctacacttcc tgaaacaaca gtcgttagaa gaagaggaag atctccaaga 3660
agaagaacac caagtcctag aagaagaaga tctcaatcac caagaagaag aagaagtcaa 3720
tctagagaat ctcaatgttg a 3741
<210> 60
<211> 96
<212> DNA
<213> 人工序列
<220>
<223> 编码的TPA
<400> 60
atggatgcta tgaagcgagg actttgttgt gttttgcttc tttgtggtgc tgtgtttgtt 60
tctccatctc aagaaattca tgccagattc agaaga 96
<210> 61
<211> 882
<212> DNA
<213> 人工序列
<220>
<223> 疫苗构建体
<400> 61
atgggaggct ggtcatctaa acctagacaa ggcatgggaa caaatctttc tgttcctaat 60
cctttgggat tctttcctga tcatcaattg gatccagcat ttggagcaaa tagtaacaat 120
ccagattggg actttaaccc aaacaaagat cattggccag aagctaatca agttggagca 180
tctaaaggtg gaaaaagtgg aatggaaaac actacatctg gatttcttgg acctttgctt 240
gttcttcaag ctggattttt cctgttgaca agaatactta caattcctca atcactggat 300
tcttggtgga caagtcttaa ttttcttgga ggtgctccta catgtcctgg acaaaattct 360
caatctccaa cttctaatca ttctcctaca tcttgtcctc caatttgtcc tggatataga 420
tggatgtgtc ttagaagatt cattatcttt cttttcatac tgctgctgtg tctgattttc 480
cttcttgttt tgttggatta tcagggaatg cttcctgttt gtcctttgct tcctggaact 540
tctacaacaa gtacaggacc ttgtaaaaca tgtacaattc cagcacaggg aacatctatg 600
tttccaagtt gttgttgtac aaaaccttct gatggaaatt gcacatgtat tcctattcca 660
agttcttggg catttgctag atttctttgg gaatgggctt ctgttagatt cagttggttg 720
tctcttttgg ttccatttgt tcagtggttt gttggattgt ctcctacagt ttggctttct 780
gttatttgga tgatgtggta ttggggacct tctctttaca atattttgag tccttttctc 840
cctttgctgc caattttctt ttgtctttgg gtttacattt ga 882

Claims (45)

1.一种多HBV免疫原病毒载体疫苗,其包含:
包含免疫原表达盒的病毒载体,其中,由所述表达盒编码的蛋白的表达设置为由启动子驱动,其中,所述免疫原表达盒编码:
a)HBV核心;
b)修饰的HBV聚合酶(Pmut),其中,所述修饰是对野生型HBV聚合酶的突变以基本上除去聚合酶功能;
c)HBV表面抗原(HbsAg);和
d)基因间序列,其设置为导致至少所述HBV表面抗原(HbsAg)表达为与所述HBV核心和所述修饰的HBV聚合酶(Pmut)分离的蛋白,
其中,所述基因间序列在编码所述HBV核心和所述修饰的HBV聚合酶(Pmut)的序列的下游(3’)和编码所述HBV表面抗原(HbsAg)的序列的上游(5’)。
2.根据权利要求1所述的多HBV免疫原病毒载体疫苗,其中,所述基因间序列包含切割结构域、IRES(内部核糖体进入位点)、剪接信号或次级启动子。
3.根据权利要求1所述的多HBV免疫原病毒载体疫苗,其中,所述基因间序列包含切割结构域;
任选地其中,所述切割结构域包含核糖体跳跃切割结构域;
进一步任选地其中,所述切割结构域包含弗林蛋白酶2A(F2A)肽序列或其功能性变体、或由其组成。
4.根据权利要求1所述的多HBV免疫原病毒载体疫苗,其中,所述基因间序列包含促进至少所述表面抗原(HbsAg)表达的次级启动子。
5.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒进一步编码HBV前核心(PreC)。
6.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒进一步编码HBV PreS1和/或其截短形式。
7.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒进一步编码HBV PreS2。
8.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒编码HBV前核心(PreC)和HBV PreS1以及截短形式的PreS1。
9.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒能够表达HBV e-抗原。
10.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述HBV核心和修饰的聚合酶(Pmut)设置成表达为融合蛋白。
11.根据权利要求5-10所述的多HBV免疫原病毒载体疫苗,其中,所述HBV前核心、HBV核心和修饰的聚合酶(Pmut)设置成表达为融合蛋白。
12.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒不编码HBV X蛋白。
13.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒包含具有以下序列的核酸:
SEQ ID NO:46(SIi-HBV-CPmutS)或其变体;
SEQ ID NO:47(SIi-HBV-SCPmut)或其变体;
SEQ ID NO:48(SIi-HBV-CPmutPreS-S(sh))或其变体;
SEQ ID NO:49(SIi-HBV-CPmutPreS-TPA-S(sh))或其变体;SEQ
ID NO:24(MVA-SIi-HBV-PreS-Pmut-C-S(sh))或其变体;或者
SEQ ID NO:27或SEQ ID NO:58(MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh))或其变体。
14.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述病毒载体编码以下氨基酸序列:
SEQ ID NO:3(SIi-HBV-CPmutS)或其变体。
SEQ ID NO:11(SIi-HBV-SCPmut)或其变体。
SEQ ID NO:13(SIi-HBV-CPmutPreS-S(sh))或其变体。
SEQ ID NO:25(SIi-HBV-CPmutPreS-TPA-S(sh))或其变体。
SEQ ID NO:23(MVA-SIi-HBV-PreS-Pmut-C-S(sh))或其变体。
SEQ ID NO:26(MVA-SIi-HBV-PreS-Pmut-C-TPA-S(sh))或其变体。
15.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述病毒载体包含腺病毒载体或修饰的安卡拉痘苗(MVA)载体。
16.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述病毒载体包含E组猿猴腺病毒载体。
17.根据前述权利要求中任意一项所述的多HBV免疫原病毒载体疫苗,其中,所述启动子编码在所述免疫原表达盒中,例如,所述启动子编码在所述免疫原表达盒的5'端或与5'端相邻;或者
其中,将所述启动子编码为所述免疫原表达盒外部的病毒载体核酸的一部分。
18.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述启动子促进所述免疫原表达盒的全部编码蛋白的表达。
19.根据权利要求1-17所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒包含次级启动子,其中所述启动子是初级启动子,其设置为促进至少所述HBV核心和修饰的聚合酶(Pmut)的表达,并且不促进设置为由所述次级启动子单独促进的所述HBV表面抗原(HbsAg)的表达。
20.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述启动子包含CMV启动子或痘病毒启动子。
21.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述HBV核心包含全长野生型HBV核心序列、或由其组成。
22.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述修饰的HBV聚合酶(Pmut)不是截短形式的HBV聚合酶(即相对于野生型HBV聚合酶是全长)。
23.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述修饰的HBV聚合酶(Pmut)包含序列SEQ ID NO:8或其变体、或由其组成。
24.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述HbsAg包含全长野生型HbsAg序列或其变体、或由其组成。
25.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒编码截短形式的HBV PreS1,并且所述截短的PreS1设置为表达与所述HBV表面抗原(S/HbsAg)的融合蛋白。
26.根据权利要求25所述的多HBV免疫原病毒载体疫苗,其进一步包含在所述截短的PreS1和表面抗原(S/HbsAg)之间提供的接头序列。
27.根据权利要求25或26所述的多HBV免疫原病毒载体疫苗,其中,将具有融合的表面抗原的所述截短的PreS1编码在所述基因间序列的下游(3’)。
28.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述表达盒编码NΔPreS1和PreS2融合序列。
29.根据权利要求28所述的多HBV免疫原病毒载体疫苗,其中,所编码的NΔPreS1和PreS2融合序列编码在所述基因间序列的上游(5’)。
30.根据权利要求29所述的多HBV免疫原病毒载体疫苗,其中,所编码的NΔPreS1和PreS2融合序列进一步与所述修饰的聚合酶(Pmut)融合。
31.根据权利要求30所述的多HBV免疫原病毒载体疫苗,其中,在所述PreS2和修饰的聚合酶(Pmut)之间提供接头序列。
32.根据前述权利要求中任一项所述的多HBV免疫原病毒载体疫苗,其中,所述免疫原表达盒进一步编码肽佐剂。
33.根据权利要求32所述的多HBV免疫原病毒载体疫苗,其中,所述肽佐剂包含TPA(组织纤溶酶原活化剂)或人或非人不变链(Ii)或其片段。
34.根据权利要求32所述的多HBV免疫原病毒载体疫苗,其中,在融合蛋白中提供的一种或多种或全部蛋白/抗原序列之间编码接头残基。
35.一种包含HBV免疫原表达盒或由其组成的核酸,其中,所述免疫原表达盒编码:
a)HBV核心;
b)修饰的HBV聚合酶(Pmut),其中,所述修饰是对野生型HBV聚合酶的突变以基本上除去聚合酶功能;
c)HBV表面抗原(HbsAg);和
d)基因间序列,其设置为导致至少所述HBV表面抗原(HbsAg)表达为与所述HBV核心和所述修饰的HBV聚合酶(Pmut)分离的蛋白,
其中,所述基因间序列在编码HBV核心和修饰的HBV聚合酶(Pmut)的序列的下游(3’)和编码HBV表面抗原(HbsAg)的序列的上游(5’)。
36.根据权利要求35所述的核酸,其中,所述免疫原表达盒进一步编码启动子。
37.根据权利要求35或36所述的核酸,其中,在非病毒载体中分离或提供所述免疫原表达盒。
38.一种包含根据权利要求1-34中任一项所述的病毒载体或根据权利要求35-37中任一项所述的核酸的组合物,任选地其中,所述组合物是药学上可接受的组合物。
39.根据权利要求38所述的组合物,其进一步包含另一种治疗或预防活性成分和/或佐剂。
40.根据权利要求38或39所述的组合物,其中,所述组合物包含药学上可接受的载体,和/或其中所述组合物是疫苗组合物。
41.根据权利要求38-40中任一项所述的组合物、根据权利要求1-34中任一项所述的病毒载体或根据权利要求35-37中任一项所述的核酸在预防或治疗受试者的HBV感染中的用途,任选地其中,所述用途是作为疫苗。
42.一种治疗或预防HBV感染的方法,其包括将根据权利要求38-40中任一项所述的组合物、根据权利要求1-34中任一项所述的病毒载体或根据权利要求35-37中任一项所述的核酸施用于受试者。
43.根据权利要求41所述的组合物用途或根据权利要求42所述的方法,其中,将所述用途或施用与另一种治疗或预防活性成分的用途或施用组合。
44.一种初免加强接种疫苗试剂盒,其包含:
-初免接种疫苗,其包含根据权利要求38-40中任一项所述的组合物、根据权利要求1-34中任一项所述的病毒载体或根据权利要求35-37中任一项所述的核酸;和
-加强接种疫苗,其包含根据权利要求38-40中任一项所述的组合物、根据权利要求1-34中任一项所述的病毒载体或根据权利要求35-37中任一项所述的核酸。
45.根据权利要求44所述的初免和加强接种疫苗试剂盒,其中,所述初免和加强接种疫苗包含不同的病毒载体。
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