CN110869047A - 塞内卡病毒a免疫原性组合物及其方法 - Google Patents

塞内卡病毒a免疫原性组合物及其方法 Download PDF

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CN110869047A
CN110869047A CN201880045810.5A CN201880045810A CN110869047A CN 110869047 A CN110869047 A CN 110869047A CN 201880045810 A CN201880045810 A CN 201880045810A CN 110869047 A CN110869047 A CN 110869047A
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A·V·耶尔
A·R·帕特森
J·G·维多利亚
E·M·沃恩
L·A·赫尔南德斯
J·L·英格利希
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Boehringer Ingelheim Animal Health USA Inc
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Abstract

本发明涉及杀死的/灭活的和/或重组的塞内卡病毒A免疫原性组合物和疫苗，以及用此类免疫原性组合物和疫苗预防或治疗有需要的动物的方法。

Description

塞内卡病毒A免疫原性组合物及其方法
序列表
本申请含有根据37C.F.R.1.821–1.825的序列表。本申请所附的序列表通过引用整体并入本文。
发明背景
A.技术领域
本发明涉及塞内卡谷病毒A或塞内卡病毒A(SVA)，及其作为免疫原性组合物或疫苗以治疗受塞内卡病毒A感染的动物的用途。
B.相关技术描述
SVA是微小核糖核酸病毒科(Picornaviridae)内的无包膜、单链、正义RNA病毒。口蹄疫病毒(FMDV)和猪水泡病病毒(SVDA)也是微小核糖核酸病毒科的成员。
该病毒最初作为来自细胞培养基的污染物被发现(参见Hales，L.M.等人，Complete genome sequence analysis of Seneca Valley virus-001，a noveloncolytic picornavirus.J Gen Virol，2008.89(Pt 5)：第1265-75页，通过引用整体并入本文)。然而，已在猪、牛、鼠和人中检测到针对该病毒的中和抗体(参见Knowles，N.J.等人，Epidemiology of Seneca Valley Virus:Identification and Characterization ofIsolates from Pigs in the United States，in The Northern Lights EUROPIC 2006-14th meeting of the European Study Group on the Molecular Biology ofPicornaviruses.2006:Saairselka，Inari，芬兰，通过引用整体并入本文)。感染后报告的临床体征包括口鼻部和冠状带上的水泡病变，急性跛行，冠状带溃疡和蹄脱落(Singh，K.等人，Seneca Valley Virus and vesicular lesions in a pig with idiopathicvesicular disease.J Vet Sci Technol，2012.3(6)，以及Pasma，T.，S.Davidson和S.L.Shaw，Idiopathic vesicular disease in swine in Manitoba.CVJ，2008.49:第84-85页，两者均通过引用整体并入本文)。在2016年，当细胞培养繁殖的SVA分离株用于接种常规动物，并且在接种后四天观察到水泡病变时，Koch的假设得以实现(Montiel，N.等人，Vesicular Disease in 9-Week-Old Pigs Experimentally Infected with SenecavirusA.Emerg Infect Dis，2016.22(7)：第1246-8页，通过引用整体并入本文)。
US 8,039,606描述了塞内卡谷病毒治疗肿瘤的用途。然而，这种塞尼卡谷病毒不同于本发明的SVA。
在美国、加拿大、澳大利亚、意大利、新西兰和巴西，已存在无法解释的SVA病例增加。进一步地，由于临床体征与FMDV的相似性，这种病毒引起了养猪业的兴趣。兽医生物制品中心(Center for Veterinary Biologics)(CVB)通知16-03确认，CVB对许可用于SVA病毒的生物制品和/或预防剂感兴趣。
发明内容
本发明提供了克服本领域缺陷的免疫原性组合物、疫苗和相关方法。所述组合物和方法提供了免疫原性组合物，其包括SVA的无包膜(+)单链RNA病毒的灭活/杀死的和/或重组形式。特别地，本申请提供了用于在猪中生成免疫应答的疫苗，用于保护免受与塞内卡病毒A相关的疾病。本文的塞内卡病毒A分离株NAC#20150909(SEQ ID NO：1、SEQ ID NO：2和/或SEQ ID NO：3)从由5月龄的猪收集的水泡液中分离，所述猪显示出在口鼻部和冠状带上的水泡病变。
本发明的免疫原性组合物和疫苗包含SEQ ID NO：1、SEQ ID NO：2和/或SEQ IDNO：3。
本发明的示例性组合物包含SEQ ID NO：3的多肽序列或其对SVA具有免疫反应性的片段。
本发明的免疫原性组合物和疫苗包含SVA抗原，在一个非限制性实例中，所述SVA抗原经由重组杆状病毒在昆虫细胞中表达，所述重组杆状病毒表达经修饰的SVA P1、2A，部分2B和3B、以及3C蛋白酶，例如编码氨基酸序列(SEQ ID NO：19)的经修饰的SVA核酸序列(SEQ ID NO：18)，并且通常还包括佐剂。疫苗还可以包括其它组分，例如防腐剂、稳定剂和针对其它猪病原体的抗原。
适用于本发明的优选的P1-2A-P3核酸序列是编码P1-2A-P3多肽的多核苷酸，所述多核苷酸与SEQ ID NO：18、20、22、24、32和33具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％或89％，更优选至少90％、91％、92％、93％或94％，且最优选至少95％、96％、96.1％、96.2％、96.3％、96.4％、96.5％、96.6％、96.7％、96.8％、96.9％、97％、97.1％、97.2％、97.3％、97.4％、97.5％、97.6％、97.7％、97.8％、97.9％、98％、98.1％、98.2％、98.3％、98.4％、98.5％、98.6％、98.7％、98.8％、98.9％、99％、99.1％、99.2％、99.3％、99.4％、99.5％、99.6％、99.7％、99.8％、99.9％的序列相同性。“如本文使用的，应特别理解术语“与SEQ ID NO：X的序列相同性”或“相同SEQ ID NO：X”分别等价于术语“在SEQ ID NO：X的长度上与SEQ ID NO：X的序列相同性”或“在SEQ ID NO：X的长度上与SEQ IDNO：X的序列相同”，分别地，其中在此上下文中，“X”是选自18、20、22、24、32和33”的任何整数。
适用于本发明的优选P1-2A-P3多肽是具有SEQ ID NO:19、21、23、25、27和29中所示的序列的多肽，与SEQ ID NO:19、21、23、25、27和29具有至少80％的同源性，例如与SEQID NO:19、21、23、25、27和29具有至少85％的同源性，例如与SEQ ID NO:19、21、23、25、27和29具有至少85％的同源性，例如与SEQ ID NO:19、21、23、25、27和29具有至少90％的同源性，例如与SEQ ID NO:19、21、23、25、27和29具有至少95％、至少98％或至少99％的同源性。
在另一个方面，本发明提供了编码一种或多种多肽、抗体构建体或抗体缀合物的核酸序列。编码多肽的基因序列包含与SEQ ID NO：1或SEQ ID NO：2的序列至少95％、90％、85％或甚至80％同源和/或相同的核酸序列，或其编码对SVA具有免疫反应性的多肽的片段。本发明的示例性核酸序列包括SEQ ID NO：1、SEQ ID NO：2及其编码对SVA具有免疫反应性的多肽的片段的任何一种序列。
此外，如本文使用的，本发明的多肽包括但不限于包含以下的多肽：
i)包含SEQ ID NO：3的氨基酸序列的多肽；
ii)与i)的多肽至少80％同源和/或相同的多肽；
iii)i)和/或ii)的多肽的片段；
iv)i)或ii)的多肽；
v)iii)或iv)的片段，其包含SEQ ID NO：3的序列中包括的至少5个，优选8个，更优选10个，甚至更优选15个邻接氨基酸；
vi)由包含SEQ ID NO：1或2的序列的多核苷酸编码的多肽；
vii)由与vi)的多核苷酸至少80％同源或相同的多核苷酸编码的多肽；
viii)由多核苷酸编码的蛋白质片段，所述多核苷酸包含SEQ ID NO：1或SEQ IDNO：2的序列中包括的至少15个，优选24个，更优选30个，甚至更优选45个邻接核苷酸。
包含如本文定义的至少一种或多种SVA多肽的本发明的免疫原性组合物可以进一步包含生理学可接受的媒介物，例如药学或兽医学可接受的载体、佐剂或其组合。
本文提供的任何SVA多肽、或者包含本文提供的这些SVA多肽中的一种或多种的任何免疫原性组合物可以用作药物，优选用作疫苗或免疫原性组合物，最优选用于对象针对SVA感染的预防或治疗。
本领域技术人员将理解，本文使用的组合物可以掺入已知的可注射的、生理学可接受的无菌溶液。为了制备用于肠胃外注射或输注的即用溶液，等渗水溶液，例如盐水或血浆蛋白溶液是可容易获得的。另外，本发明的免疫原性和疫苗组合物可以包括兽医学可接受的载体、稀释剂、等渗剂、稳定剂或佐剂。
本发明的方法包括但不限于在对象中引发针对SVA感染的免疫应答的方法，其包括向对象施用包含如本文定义的一种或多种SVA多肽的免疫原性组合物的步骤。本发明的组合物可以用于治疗或可替代地用于预防SVA感染。优选地，这种免疫应答减少与SVA血清型感染相关或由其引起的一种或多种临床症状的发生率或严重性。
在本文中，合适的对象和需要对其施用本发明的组合物的对象包括需要预防或治疗病毒相关感染、疾病或状况的动物。其中通过使用本发明的组合物或方法刺激免疫应答的动物包括家畜，例如猪、牛、山羊和绵羊。优选动物包括猪科动物、鼠科动物、马科动物、兔形目动物和牛科动物。最优选地，在猪中刺激免疫应答。
本发明还提供了减少与SVA感染相关或由其引起的一种或多种临床体征的发生率或严重性的方法，其包括施用本发明免疫原性组合物的步骤，所述免疫原性组合物包含如本文提供的一种或多种SVA肽以及优选包含载体分子，使得相对于仍未接受如随同提供的免疫原性组合物的对象，SVA感染的临床体征的发生率或严重性减少至少10％，优选至少20％，甚至更优选至少30％，甚至更优选至少50％，甚至更优选至少70％，最优选至少100％。
此类临床体征包括水疱病，例如位于口鼻部、口腔粘膜和/或其中皮肤和蹄壁相交处(冠状带)的开放或闭合性水泡或病变，甲床出血，伴随在冠状带处或周围的发红和肿胀的突然跛行；以及突然停止进食，嗜睡，厌食和/或发烧高达华氏105°(摄氏～40.6°)的繁殖雌性。
看起来存在新生仔猪(小于7天)的死亡率中的短期(4-10天)增加，所述新生仔猪可能具有或没有与之相关的腹泻。关于短时间段的发病率和死亡率估计为30-70％。在调查新生儿死亡率的增加时通常注意到育龄动物中的水泡病变。在猪中导致口鼻部和冠状带水泡的这类感染也已被称为猪中的特发性水泡病。
根据一个进一步方面，本发明还涉及用于预防SVA感染的方法，其中所述SVA感染可以由塞内卡谷病毒A引起，所述方法包括施用本发明的免疫原性组合物的步骤，所述免疫原性组合物包含如本文提供的一种或多种SVA肽。
本发明还提供了制备本文提供的任何免疫原性组合物的方法，该方法包括将如本文提供的一种或多种SVA肽与载体分子混合，优选地使得一种或多种SVA肽和载体分子是彼此共价偶联或缀合的。此类缀合物可以是多价或单价的。多价组合物或疫苗包括多重SVA肽与载体分子的免疫缀合。在一个进一步方面，本发明提供了产生一种或多种SVA肽的方法，该方法包括用核酸分子转化宿主细胞，优选原核细胞，例如大肠杆菌(E.coli)，所述核酸分子编码如本文提供的任何SVA肽。可替代地，宿主细胞可以是真核细胞，例如动物细胞、原生生物细胞、植物细胞或真菌细胞。优选地，真核细胞是哺乳动物细胞，例如CHO、BHK或COS，或真菌细胞，例如酿酒酵母(Saccharomyces cerevisiae)，或昆虫细胞，例如Sf9。
本发明的另一个方面提供了产生一种或多种SVA肽的方法，所述一种或多种SVA肽诱导针对SVA的免疫应答。这包括培养经转化的表达载体，其编码并表达本文公开的一种或多种SVA肽。表达的蛋白质或被表达生物保留或被分泌到培养基内。在足以产生能够诱导针对SVA的免疫应答的SVA肽的条件下进行表达。
还提供了经由表达经修饰的SVA P1-2A-P3蛋白的重组杆状病毒，产生在昆虫细胞中生成的重组表达的P1-2A-P3抗原疫苗的方法。在一个示例性实施方案中，该方法包括将SVA P1-2A-P3序列克隆到载体pVL1393(BD Biosciences)内，并且共转染Sf9昆虫细胞。对于灭活的重组SVA材料，使用5mM BEI将SVA杆状病毒收获物灭活24小时，澄清且进行0.45μm过滤。通常，灭活的病毒例如通过浓缩以及与其它组分共混进行进一步加工，以产生商业制剂。例如，可以将含有灭活病毒的流体浓缩，并且与佐剂和/或针对一种或多种其它猪病原体的抗原共混。
制备本发明的组合物的方法可以进一步包括将一种或多种SVA肽或灭活的全病毒制剂和载体分子的缀合物与生理学可接受的媒介物，例如药学或兽医学可接受的载体、佐剂或其组合混合。本领域技术人员将认识到，媒介物、佐剂或组合的选择尤其由递送途径、个人偏好和动物物种决定。
在另一个方面，本发明提供了诊断对象中的SVA感染的方法。该方法包括提供一种或多种SVA肽；使一种或多种SVA肽与得自对象的样品接触；并且如果在样品中检测到能够结合一种或多种SVA肽的抗体，则将对象鉴定为具有SVA感染。
在另一个方面，本发明提供了确定对象先前已暴露于SVA感染并且能够表达针对SVA的免疫应答的方法。该方法包括提供一种或多种SVA肽；使一种或多种SVA肽与得自对象的样品接触；并且如果在样品中检测到能够结合一种或多种SVA肽的抗体，则将对象鉴定为具有SVA感染。
本发明还提供了包含以下的试剂盒：免疫原性组合物，所述免疫原性组合物包含一种或多种SVA肽，优选地连同载体分子一起；用于包装免疫原性组合物的容器；一组印刷说明书；以及能够将免疫原性组合物施用于动物的分配器。任选地，一种或多种SVA肽和载体分子可以包装为缀合物或分开的化合物。当分开供应时，还供应了使一种或多种SVA肽和载体分子缀合的工具，以及适当的印刷说明书。
本发明还提供了用于给动物接种疫苗的试剂盒，其包括一组印刷说明书；能够向动物施用包含一种或多种SVA肽的本文提供的免疫原性组合物的分配器；并且其中至少一种SVA肽针对与SVA感染相关的至少一种疾病有效地免疫动物。优选地，一种或多种SVA肽选自本文提供的那些。本发明的试剂盒可以进一步包含兽医学可接受的载体、佐剂或其组合。
本发明的试剂盒中的分配器能够将其内容物作为液滴分配；并且当鼻内、经口、皮内或肌内施用于动物时，试剂盒中包括的如本文提供的包含SVA肽的免疫原性组合物，能够减少SVA感染的至少一种临床体征的严重性。优选地，与未治疗的受感染动物相比，临床体征的严重性减少至少10％，优选至少20％，甚至更优选至少30％，甚至更优选至少50％，甚至更优选至少70％，最优选至少100％。
还公开了用于治疗或预防由SVA引起的感染的方法。该方法包括向对象施用有效量的本发明的免疫原性组合物，其中所述治疗或预防选自减少SVA感染的体征、减少SVA感染的临床体征的严重性或发生率、减少对象因SVA感染的死亡率及其组合。
本发明的组合物进一步包含兽医学可接受的载体、佐剂或其组合。此类组合物可以用作疫苗，并且包含灭活疫苗。此类疫苗引起针对与SVA相关的至少一种疾病的保护性免疫应答。
本领域技术人员将理解，本文使用的组合物可以掺入已知的可注射的、生理学可接受的无菌溶液。为了制备用于肠胃外注射或输注的即用溶液，等渗水溶液，例如盐水或血浆蛋白溶液是可容易获得的。另外，本发明的免疫原性和疫苗组合物可以包括药学或兽医学可接受的载体、稀释剂、等渗剂、稳定剂或佐剂。
本发明的方法还可以包括将本发明的组合物与兽医学可接受的载体、佐剂或其组合混合。本领域技术人员将认识到，载体、佐剂或组合的选择尤其由递送途径、个人偏好和动物物种决定。
还公开了用于治疗或预防由SVA引起的感染的方法。该方法包括向动物施用有效量的本发明的免疫原性组合物，其中所述治疗或预防选自减少SVA感染的体征、减少SVA感染的临床体征的严重性或发生率、减少动物因SVA感染的死亡率及其组合。
优选的施用途径包括鼻内、经口、皮内和肌内。经由肌内途径的施用是优选的，最优选在单一剂量中。本领域技术人员将认识到，本发明的组合物也可以在两个或更多个剂量中，以及通过其它施用途径来施用。例如，此类其它途径包括皮下、皮内、静脉内、血管内、动脉内、腹膜内、鞘内、气管内、皮内、心内、叶内、髓内、肺内或阴道内。取决于治疗的所需持续时间和有效性，本发明的组合物可以一次或几次，以及间歇地施用，例如在每天一次的基础上共几天、几周或几个月，并且以不同的剂量。
本发明还提供了用于给动物接种疫苗的试剂盒，其包括一组印刷说明书；能够向动物施用疫苗的分配器；以及来自SVA培养物的至少一种分离株。本发明的试剂盒可以进一步包含兽医学可接受的载体、佐剂或其组合。
本发明的试剂盒中的分配器能够将其内容物作为液滴分配；并且当鼻内、经口、皮内或肌内施用于动物时，试剂盒中包括的分离株能够减少SVA感染的至少一种临床体征的严重性。在一些试剂盒中，分离株还能够减少SVA感染的至少一种临床体征的严重性。优选地，与未治疗的受感染动物相比，临床体征的严重性减少至少10％。
本发明的其它目的、特征和优点根据下述详细描述将变得显而易见。然而，应该理解，详细描述和具体实例虽然指示了本发明的优选实施方案，但仅通过举例说明的方式给出，因为在本发明的精神和范围内的各种改变和修改根据该详细描述对于本领域技术人员将变得显而易见。
附图说明
图1显示了用于杆状病毒表达系统的SVVP13C构建体设计(A)(SEQ ID NO：18)，以及SVVP 13C-CO(密码子优化的)构建体设计(B)(SEQ ID NO：20)。
图2显示了用于杆状病毒表达系统的SVVP1-His-sIRES-SVV3C构建体设计(A)(SEQID NO：32)，以及SVVP1CO-His-sIRES-SVV3C(密码子优化的)构建体设计(B)(SEQ ID NO：33)。
图3显示了用于杆状病毒表达系统的突变VP3/VP1切割位点的SVVP13C VP3/VP1构建体设计(A)(SEQ ID NO：22)，以及SVVP13CD构建体设计(B)(SEQ ID NO：24)。
图4显示了与用抗α-SVV VP1、抗α-SVV VP2和抗α-SVV VP3交叉吸收的兔多克隆抗体检测的天然SVV抗原相比，BaculoFBU/SVVP13C(A)(SEQ ID NO：18)和BaculoFBU/SVVP13C-CO(B)(SEQ ID NO：20)上清液样品的蛋白质印迹。泳道A是蛋白质标准，泳道1是SVV Baculo收获物上清液，泳道2是SVV抗原(SEQ ID NO：3)，且泳道3是Baculo收获物上清液阴性对照。预期的条带大小：全长SVV P1＝约95kDa(SEQ ID NO：19，氨基酸1-859)，VP1＝约29kDa(SEQ ID NO：19，氨基酸596-859)，VP2-约32kDa(SEQ ID NO：19，氨基酸73-356)，VP3＝约26kDa(SEQ ID NO：19，氨基酸357-595)。
图5显示了用抗α-SVV VP1、α-SVV VP2和α-SVV VP3兔多克隆抗体的天然SVV病毒蔗糖级分(A)和BauloFBU/SVVP13C蔗糖级分(B)的蛋白质印迹。泳道A是蛋白质标准，泳道1-10是蔗糖级分1-10，N-BaculoFBU/无插入片段阴性对照，P是阳性对照天然灭活的SVV，且S是关于蔗糖梯度的起始样品。预期的条带大小：全长SVV P1＝约95kDa(SEQ ID NO：19，氨基酸1-859)，VP1＝约29kDa(SEQ ID NO：19，氨基酸596-859)，VP2-约32kDa(SEQ ID NO：19，氨基酸73-356)，VP3＝约26kDa(SEQ ID NO：19，氨基酸357-595)。
图6显示了用α-SVV VP1(顶部行)和α-SVV VP3(底部行)兔多克隆抗体的BaculoFBU/SVVP13C(SEQ ID NO：18)和BaculoFBU/VVP13C VP3/VP1(SEQ ID NO：22)上清液收获物的蛋白质印迹。泳道A-蛋白质标准，泳道1-SVV Baculo收获物上清液，泳道2-SVV抗原和泳道3-Baculo收获物上清液阴性对照。
图7显示了用抗SVV VP1、抗SVV VP2和抗SVV VP3兔多克隆抗体的BaculoFBU/VVP13C VP3/VP1(SEQ ID NO：22)蔗糖级分的蛋白质印迹。泳道A是蛋白质标准，N是BaculoFBU/无插入片段天然对照，P是阳性对照天然灭活的SVV(SEQ ID NO：3)，S是重悬浮于TBS中的SVVP13C VP3/VP1(SEQ ID NO：22)团块，且泳道1-9是蔗糖级分1-9。全长SVV P1＝约95kDa(SEQ ID NO：19，氨基酸1-859)，VP1＝约29kDa(SEQ ID NO：19，氨基酸596-859)，VP2-约32kDa(SEQ ID NO：19，氨基酸73-356)，VP3＝约26kDa(SEQ ID NO：19，氨基酸357-595)。
图8显示了用抗SVV VP1、抗SVV VP2和抗SVV VP3兔多克隆抗体检测的BaculoFBU/VVP13CD(SEQ ID NO：24)上清液收获物的蛋白质印迹。泳道A是蛋白质标准，泳道1是SVVBaculo收获物上清液，泳道2是SVV抗原(SEQ ID NO：3)，且泳道3是Baculo收获物上清液阴性对照。预期的条带大小：全长SVV P1＝约95kDa(SEQ ID NO：19，氨基酸1-859)，VP1＝约29kDa(SEQ ID NO：19，氨基酸596-859)，VP2-约32kDa(SEQ ID NO：19，氨基酸73-356)，VP3＝约26kDa(SEQ ID NO：19，氨基酸357-595)。
图9显示了用抗SVV VP1、抗SVV VP2和抗SVV VP3兔多克隆抗体的BaluloFBU/SVVP13CD(SEQ ID NO：24)蔗糖级分的蛋白质印迹。泳道A是蛋白质标准，泳道1是SVVBaculo收获物上清液，泳道N是BaculoFBU/无插入片段阴性对照，P是阳性对照天然灭活的SVV(SEQ ID NO.3)，S是重悬浮于TBA中的SVVP13CD(SEQ ID NO.25)团块，且泳道1-10是蔗糖级分1-10。预期的条带大小：全长SVV P1＝约95kDa(SEQ ID NO：19，氨基酸1-859)，VP1＝约29kDa(SEQ ID NO：19，氨基酸596-859)，VP2-约32kDa(SEQ ID NO：19，氨基酸73-356)，VP3＝约26kDa(SEQ ID NO：19，氨基酸357-595)。
图10显示了BaculoFBU/SVVP13C(A)(SEQ ID NO:18)、BaculoFBU/SVVP13CD(A)(SEQ ID NO:24)和BaculoFBU/SVVP13CVP3/VP1(B)(SEQ ID NO:22)的蛋白质印迹。第3天可溶性级分具有α-SVVVP1、α-SVVVP2和α-SVVVP3兔多克隆抗体。用于BaculoFBU/SVVP13C和BaculoFBU/SVVP13CD(C)的SDS-PAGE凝胶。泳道A-蛋白质标准，泳道P-阳性对照天然SVV抗原，泳道1-第3天可溶性级分SVVP13C，泳道2-第3天可溶性级分SVVP13CD，泳道3-第3天可溶性级分SVVP13C VP3/VP1和泳道N-阴性对照BaculoFBU/无插入片段可溶性级分。预期的条带大小：全长SVV P1＝约95kDa(SEQ ID NO：19，氨基酸1-859)，VP1＝约29kDa(SEQ ID NO：19，氨基酸596-859)，VP2-约32kDa(SEQ ID NO：19，氨基酸73-356)，VP3＝约26kDa(SEQ IDNO：19，氨基酸357-595)。
图11显示了用抗α-SVV VP1、抗α-SVV VP2和抗α-SVV VP3兔多克隆抗体的第3天可溶性BaculoFBU/SVVP13C(SEQ ID NO:18)、BaculoFBU/SVVP13CD(SEQ ID NO:24)和BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO:22)的蔗糖级分的蛋白质印迹。泳道A是蛋白质标准，P是阳性对照天然灭活的SVV，泳道1-11是蔗糖级分1-11，且N是阴性对照BaculoFBU/无插入片段可溶性级分。预期的条带大小：全长SVV P1＝约95kDa(SEQ ID NO：19，氨基酸1-859)，VP1＝约29kDa(SEQ ID NO：19，氨基酸596-859)，VP2-约32kDa(SEQ ID NO：19，氨基酸73-356)，VP3＝约26kDa(SEQ ID NO：19，氨基酸357-595)。
图12显示了按研究天数和组的最小均方直肠温度(℃)。
图13显示了按组和天数，在血清中的组中值log10基因组拷贝/mL SVA RNA。
发明详述
除非另有说明，否则本发明的实践采用分子生物学、微生物学、重组DNA技术、蛋白质化学和免疫学的常规技术，其在本领域的技术内。此类技术在文献中得到充分解释。参见例如，Sambrook，Fritsch&Maniatis，Molecular Cloning:A Laboratory Manual，第I、II和III卷，第二版(1989)；DNA Cloning，第I和II卷(D.N.Glover编辑1985)；OligonucleotideSynthesis(M.J.Gait编辑1984)；Nucleic Acid Hybridization(B.D.Hames&S.J.Higgins编辑1984)；Animal Cell Culture(R.K.Freshney编辑1986)；Immobilized Cells andEnzymes(IRL press，1986)；Perbal，B.，A Practical Guide to Molecular Cloning(1984)；the series，Methods In Enzymology(S.Colowick和N.Kaplan编辑，AcademicPress，Inc.)；Protein purification methods–a practical approach(E.L.V.Harris和S.Angal，编辑，IRL Press at Oxford University Press)；以及Handbook ofExperimental Immunology，第I-IV卷(D.M.Weir和C.C.Blackwell编辑，1986，BlackwellScientific Publications)。
在详细描述本发明之前，应理解，本发明并不限于特定的DNA、多肽序列或过程参数，因为这些当然可以变化。还应理解，本文使用的术语仅用于描述本发明的特定实施方案的目的，并且不预期是限制性的。必须注意的是，如在本说明书和所附权利要求中使用的，单数形式“一个”、“一种”和“该/所述”包括复数指示物，除非内容另有明确规定。因此，例如，提及“抗原”包括两种或更多种抗原的混合物；提及“赋形剂”包括两种或更多种赋形剂的混合物，等等。
A.定义
除非另有定义，否则本文使用的所有技术和科学术语都具有与本发明在提交时所属领域的技术人员通常理解相同的含义。术语的含义和范围应该是明确的；然而，在任何潜在的歧义的情况下，本文提供的定义优先于任何字典或外部定义。进一步地，除非上下文另有要求，否则单数术语应该包括复数，并且复数术语应该包括单数。在本文中，除非另外说明，否则“或”的使用意指“和/或”。此外，术语“包括(including)”以及其它形式如“包括(includes)”和“包括(included)”的使用不是限制性的。本文提及的所有专利和出版物都引入本文作为参考。
“针对疾病的保护”、“保护性免疫”、“功能性免疫”和类似短语，意指通过施用本发明的一种或多种治疗组合物或其组合，而生成的针对疾病或状况的应答，其导致在已暴露于疾病或感染的非免疫对象中预期的更少的有害效应。即，感染的有害效应的严重性在接种疫苗的对象中减弱。感染在接种疫苗的对象中可以减少，减慢或可能完全预防。在本文中，当意指感染的完全预防时，它被明确陈述。如果未陈述完全预防，则该术语包括部分预防。
在本文中，“临床体征的发生率和/或严重性的减少”或“临床症状的减少”意指，但不限于与野生型感染相比，减少组中的受感染对象数目、减少或消除显示出感染的临床体征的对象数目、或者减少一个或多个对象中存在的任何临床体征的严重性。例如，它应该指病原体载量的任何减少、病原体脱落、病原体传播中的减少、或疟疾的任何临床体征症状的减少。优选地，与未接受该组合物且变得被感染的对象相比，这些临床体征在接受本发明的治疗组合物的一个或多个对象中减少至少10％。更优选地，临床体征在接受本发明的组合物的对象中减少至少20％，优选至少30％，更优选至少40％，且甚至更优选至少50％。
术语“增加的保护”在本文中意指但不限于，相对于未接种疫苗的对象的对照组，在接种疫苗的对象组中，与被传染原优选SVA感染相关的一种或多种临床症状的统计学显著减少。术语“临床症状的统计学显著减少”意指但不限于，在传染原攻击后，与未接种疫苗的对照组相比，在接种疫苗的对象组中至少一种临床症状的发生率频率低至少10％，优选20％，更优选30％，甚至更优选50％，且甚至更优选70％。
“持久保护”应该指持续至少3周，但更优选至少3个月，还更优选至少6个月的“改善功效”。在家畜的情况下，最优选持久保护应该持续直到动物在其下因肉而出售的平均年龄。
“免疫原性或免疫学组合物”指包含至少一种SVA免疫原性组合物或其免疫原性部分的物质组合物，其在宿主中引发针对该组合物的细胞或抗体介导的免疫应答的免疫学应答。在本发明的一个优选实施方案中，免疫原性组合物诱导免疫应答，并且更优选地，赋予针对SVA感染的一种或多种临床体征的保护性免疫。
如本文使用的，“免疫原性”或“抗原”指引发如本文所述的免疫应答的多肽或蛋白质。“免疫原性”SVA蛋白或多肽包括本文鉴定的任何SVA或其类似物或免疫原性片段的全长序列。术语“免疫原性片段”或“免疫原性部分”指SVA的片段或者截短的和/或取代的形式，其包括一个或多个表位并且因此引发本文所述的免疫应答。一般而言，此类截短的和/或取代的形式或片段包含来自全长SVA蛋白的至少六个邻接氨基酸。更优选地，截短的或取代的形式或片段具有来自全长SVA蛋白的至少10个，更优选至少15个，且还更优选至少19个邻接氨基酸。可以使用本领域众所周知的许多表位作图技术来鉴定此类片段。参见例如，Epitope Mapping Protocols in Methods in Molecular Biology，第66卷(GlennE.Morris编辑，1996)，Humana Press，Totowa，New Jersey。例如，线性表位可以通过以下进行测定：同时合成在固体支持物上的大量肽，所述肽对应于蛋白质分子的一部分，并且在肽仍附着至载体的同时，使肽与抗体反应。此类技术是本领域已知且描述的，参见例如，美国专利号4,708,871；Geysen等人(1984)Proc.Natl.Acad.Sci.USA 81:3998-4002；以及Geysen等人(1986)Molec.Immunol.23:709-715。类似地，例如通过x射线晶体学和二维核磁共振，通过测定氨基酸的空间构象，容易地鉴定构象表位。参见Epitope MappingProtocols，同上。合成抗原也包括在定义内，例如多表位、侧翼表位和其它重组或合成衍生的抗原。参见例如，Bergmann等人(1993)Eur.J.Immunol.23:2777-2781；Bergmann等人(1996)，J.Immunol.157:3242-3249；Suhrbier，A.(1997)，Immunol.and Cell Biol.75:402-408；以及Gardner等人，(1998)12th World AIDS Conference，Geneva，瑞士，1998年6月28日-7月3日。(其教导和内容全都通过引用引入本文)。
“免疫应答”或“免疫学应答”意指但不限于针对目的组合物或疫苗的细胞和/或抗体介导的免疫应答的发展。通常，免疫应答或免疫学应答包括但不限于下述效应中的一种或多种：特异性针对目的组合物或疫苗中包括的一种或多种抗原的抗体、B细胞、辅助性T细胞、抑制性T细胞和/或细胞毒性T细胞的产生或激活。优选地，宿主展示治疗性或保护性免疫学(记忆)应答，使得对新感染的抗性得以增强和/或疾病的临床严重性得以减少。通过症状数目、症状严重性中的减少、或与病原体感染相关的一种或多种症状的缺乏、病毒血症发作中的延迟、减少的病毒持续性、总体病毒载量中的减少和/或病毒排出的减少来证实此类保护。
在本文中，“特异性免疫反应性”指识别SVA感染特有的抗原，但不与严格攻击对照特有的抗原反应的免疫反应性蛋白质或多肽。
如本文使用的，“药学或兽医学可接受的载体”包括任何和所有溶剂、分散介质、包衣、佐剂、稳定试剂、稀释剂、防腐剂、抗菌剂和抗真菌剂、等渗剂、吸附延迟剂等等。在一些优选实施方案中，且尤其是包括冻干的免疫原性组合物的那些实施方案，用于在本发明中使用的稳定试剂包括用于冻干或冷冻干燥的稳定剂。
在一些实施方案中，本发明的免疫原性组合物含有佐剂。如本文使用的，“佐剂”可以包括氢氧化铝和磷酸铝、皂苷例如Quil A、QS-21(Cambridge Biotech Inc.，CambridgeMA)、GPI-0100(Galenica Pharmaceuticals，Inc.，Birmingham，AL)、油包水型乳液、水包油型乳液、水包油包水型乳液。该乳液可以特别地基于轻质液体石蜡油(欧洲药典型)；类异戊二烯油，例如角鲨烷或角鲨烯；起因于烯烃，特别是异丁烯或癸烯的寡聚化的油；含有线性烷基基团的酸或醇的酯，更特别是植物油、油酸乙酯、丙二醇二(辛酸酯/癸酸酯)、甘油三(辛酸酯/癸酸酯)或丙二醇二油酸酯；支链脂肪酸或醇的酯，特别是异硬脂酸酯。该油与乳化剂组合使用，以形成乳液。乳化剂优选为非离子型表面活性剂，特别是脱水山梨糖醇、二缩甘露醇(例如脱水甘露醇油酸酯)、二醇、聚甘油、丙二醇以及油酸、异硬脂酸、蓖麻油酸或羟基硬脂酸的酯，其任选地被乙氧基化，以及聚氧丙烯-聚氧乙烯共聚物嵌段，特别是Pluronic产品，尤其是L121。参见Hunter等人，The Theory and Practical Applicationof Adjuvants(Ed.Stewart-Tull，D.E.S.)，JohnWiley and Sons，NY，第51-94页(1995)，以及Todd等人，Vaccine 15:564-570(1997)。示例性的佐剂是由M.Powell和M.Newman，PlenumPress，1995编辑的“Vaccine Design，The Subunit and Adjuvant Approach”的第147页上描述的SPT乳液，以及在这同一本书的第183页上描述的乳液MF59。
佐剂的进一步实例是选自丙烯酸或甲基丙烯酸的聚合物，以及马来酸酐和烯基衍生物的共聚物的化合物。有利的佐剂化合物是丙烯酸或甲基丙烯酸的聚合物，其尤其与糖或多元醇的聚烯基醚交联。这些化合物通过术语卡波姆已知(Phameuropa，第8卷，第2期，1996年6月)。本领域技术人员还可以参考美国专利号2,909,462，其描述了与具有至少3个羟基基团，优选不超过8个羟基基团的多羟基化化合物交联的此类丙烯酸聚合物，至少三个羟基的氢原子被替换为具有至少2个碳原子的不饱和脂族原子团。优选的原子团是含有2至4个碳原子的那些原子团，例如乙烯基、烯丙基和其它烯键式不饱和基团。不饱和原子团本身可以含有其它取代基，例如甲基。以名称
Figure BDA0002360499750000111
(Lubrizol)销售的产品是特别合适的。它们与烯丙基蔗糖或烯丙基季戊四醇交联。其中可以提及的是Carbopol 974P、934P和971P。最优选的是Carbopol 971P的使用。在马来酸酐和烯基衍生物的共聚物中有共聚物EMA(Monsanto)，其是马来酸酐和乙烯的共聚物。这些聚合物在水中的溶解导致酸溶液，其优选被中和至生理pH，以便给出免疫原性、免疫学或疫苗组合物本身掺入其内的佐剂溶液。
进一步的合适佐剂包括但不限于尤其是RIBI佐剂系统(Ribi Inc.)，嵌段共聚物(CytRx，Atlanta GA)，SAF-M(Chiron，Emeryville CA)，单磷酰脂质A，阿夫立定脂质-胺佐剂，来自大肠杆菌的热不稳定性肠毒素(重组或其它形式)，霍乱毒素，IMS 1314或胞壁酰二肽，或者天然存在的或重组的细胞因子或其类似物或内源性细胞因子释放的刺激物。
预期可以以约100μg至约10mg/剂的量，优选以约100μg至约10mg/剂的量，更优选以约500μg至约5mg/剂，甚至更优选以约750μg至约2.5mg/剂的量，且最优选以约1mg/剂的量添加佐剂。可替代地，佐剂可以为按最终产物的体积计约0.01至50％的浓度，优选为约2％至30％的浓度，更优选为约5％至25％的浓度，还更优选为约7％至22％的浓度，且最优选为10％至20％的浓度。
“稀释剂”可以包括水、盐水、右旋糖、乙醇、甘油等等。等渗剂可以尤其包括氯化钠、右旋糖、甘露醇、山梨糖醇和乳糖。稳定剂尤其包括白蛋白和乙二胺四乙酸的碱金属盐。
“分离的”意指“通过人为”从其天然状态改变，即，如果它在自然界中出现，则它已被改变或从其原始环境中取出、或两者。例如，天然存在于活生物中的多核苷酸或多肽不是“分离的”，但是与其天然状态的共存材料分开的相同的多核苷酸或多肽是“分离的”，如该术语在本文中采用的。
“安全性”指在疫苗接种后在接种疫苗的动物中不存在不良后果，包括但不限于：基于细菌的疫苗潜在逆转为毒力，临床上显著的副作用，例如持续的全身性疾病或在疫苗施用的部位处无法接受的炎症。
如本文使用的，术语“疫苗接种(vaccination)”或“疫苗接种(vaccinating)”或其变体意指但不限于，包括施用本发明的免疫原性组合物的过程，当施用于动物时，所述免疫原性组合物在动物中引发或能够引发(直接或间接地)针对SVA的免疫应答。
在本发明的上下文中，“死亡率”指由SVA感染引起的死亡，并且包括其中感染如此严重使得对动物实施安乐死，以防止痛苦且对其生命提供人道终结的情况。
在本文中，“有效剂量”意指但不限于引发或能够引发免疫应答的抗原量，所述免疫应答在抗原施用于其的动物中产生临床体症状的减少。
如本文使用的，术语“有效量”在组合物的上下文中意指能够诱导免疫应答的免疫原性组合物的量，所述免疫应答在动物中减少感染的发生率或减轻感染的严重性或疾病的发生率。特别地，有效量指集落形成单位(CFU)/剂量。可替代地，在治疗的上下文中，术语“有效量”指这样的疗法量，其足以减少或改善疾病或病症、或者其一种或多种症状的严重性或持续时间，预防疾病或病症的前进，引起疾病或病症的消退，预防与疾病或病症相关的一种或多种症状的复发、发展、发作或进展，或者增强或改善另一种疗法或治疗剂的预防或治疗。
术语“片段”指SVA肽或编码此类SVA肽的基因的片段或者截短的和/或取代的形式，其包括一个或多个表位并且因此引发针对SVA的免疫应答。优选地，此类片段是本文提供的任何SVA肽或任何SVA基因的片段或者截短的和/或取代的形式。一般而言，此类截短的和/或取代的形式或片段包含来自全长SVA序列的至少六个邻接氨基酸。更优选地，截短的或取代的形式或片段具有来自全长SVA序列的至少10个，更优选地至少15个，且还更优选地至少19个邻接氨基酸。可以使用本领域众所周知的许多表位作图技术来鉴定此类片段。参见例如，Epitope Mapping Protocols in Methods in Molecular Biology，第66卷(GlennE.Morris编辑，1996)，Humana Press，Totowa，New Jersey。例如，线性表位可以通过以下进行测定：同时合成在固体支持物上的大量肽，所述肽对应于蛋白质分子的一部分，并且在肽仍附着至载体的同时，使肽与抗体反应。此类技术是本领域已知且描述的，参见例如，美国专利号4,708,871；Geysen等人(1984)Proc.Natl.Acad.Sci.USA 81:3998-4002；以及Geysen等人(1986)Molec.Immunol.23:709-715。类似地，例如通过x射线晶体学和二维核磁共振，通过测定氨基酸的空间构象，容易地鉴定构象表位。参见Epitope MappingProtocols，同上。合成抗原也包括在定义内，例如多表位、侧翼表位和其它重组或合成衍生的抗原。参见例如，Bergmann等人(1993)Eur.J.Immunol.23:2777-2781；Bergmann等人(1996)，J.Immunol.157:3242-3249；Suhrbier，A.(1997)，Immunol.and Cell Biol.75:402-408；以及Gardner等人，(1998)12th World AIDS Conference，Geneva，瑞士，1998年6月28日-7月3日。(其教导和内容全都通过引用引入本文)。
关于序列(例如，多肽或核酸序列)的术语“变体”预期意指基本上相似的序列。对于包含开放读码框的核苷酸序列，变体包括由于遗传密码的简并性，编码天然蛋白质的相同氨基酸序列的那些序列。变体核苷酸序列还包括合成衍生的核苷酸序列，例如通过使用定点诱变生成的那些，并且对于开放读码框，编码天然蛋白质，以及编码相对于天然蛋白质具有氨基酸取代用于密码子优化的目的的多肽的那些。一般地，使用由标准参数描述的比对程序之一，与参考序列相比，本发明的核苷酸序列变体具有至少80％、81％、82％、83％、84％、85％、86％、87％、88％或89％，更优选至少90％、91％、92％、93％或94％，且最优选至少95％、96％、96.1％、96.2％、96.3％、96.4％、96.5％、96.6％、96.7％、96.8％、96.9％、97％、97.1％、97.2％、97.3％、97.4％、97.5％、97.6％、97.7％、97.8％、97.9％、98％、98.1％、98.2％、98.3％、98.4％、98.5％、98.6％、98.7％、98.8％、98.9％、99％、99.1％、99.2％、99.3％、99.4％、99.5％、99.6％、99.7％、99.8％、99.9％的序列相同性。
如本文使用的，术语“对SVA具有免疫反应性”意指该肽或片段引发针对SVA的免疫学应答。
如本文使用的，“序列同源性”指测定两个序列的相关性的方法。为了测定序列同源性，将两个或更多个序列最佳比对，并且需要时引入缺口。然而，与“序列相同性”形成对比，当测定序列同源性时，保守氨基酸取代被视为匹配。换言之，为了获得与参考序列具有95％序列同源性的多肽或多核苷酸，参考序列中85％，优选90％，甚至更优选95％的氨基酸残基或核苷酸必须匹配或包含由另一种氨基酸或核苷酸的保守取代，或者参考序列中高达15％，优选高达10％，甚至更优选高达5％的总氨基酸残基或核苷酸的多个氨基酸或核苷酸(不包括保守取代)可以插入参考序列中。优选地，同源序列包含至少50个，甚至更优选100个，甚至更优选250个，甚至更优选地500个核苷酸的段。
“保守取代”指氨基酸残基或核苷酸由具有相似特征或性质(包括大小、疏水性等)的另一个氨基酸残基或核苷酸的取代，使得总体功能没有明显改变。
如本领域已知的，“序列相同性”指两个或更多个多肽序列、或者两个或更多个多核苷酸序列之间的关系，即参考序列以及待与参考序列进行比较的给定序列。如通过此类序列的串之间的匹配测定的，在序列已进行最佳比对以产生最高程度的序列相似性后，通过将给定序列与参考序列进行比较来测定序列相同性。在此类比对后，在逐个位置的基础上确定序列相同性，例如，如果在特定位置处核苷酸或氨基酸残基是相同的，则序列在该位置处是“相同的”。然后将此类位置相同性的总数目除以参考序列中核苷酸或残基的总数目，以给出％序列相同性。序列相同性可以通过已知方法容易地计算，所述方法包括但不限于在以下中描述的那些：Computational Molecular Biology，Lesk，A.N.，编辑，OxfordUniversity Press，New York(1988)，Biocomputing:Informatics and Genome Projects，Smith，D.W.，编辑，Academic Press，New York(1993)；Computer Analysis of SequenceData，Part I，Griffin，A.M.和Griffin，H.G.，编辑，Humana Press，New Jersey(1994)；Sequence Analysis in Molecular Biology，von Heinge，G.，Academic Press(1987)；Sequence Analysis Primer，Gribskov，M.和Devereux，J.，编辑，M.Stockton Press，NewYork(1991)；以及Carillo，H.和Lipman，D.，SIAM J.Applied Math.，48:1073(1988)，其教导通过引用引入本文。测定序列相同性的优选方法被设计为给出在测试的序列之间的最大匹配。测定序列相同性的方法被编码在测定给定序列之间的序列相同性的可公开获得的计算机程序中。此类程序的实例包括但不限于GCG程序包(Devereux，J.等人，Nucleic AcidsResearch，12(1):387(1984))，BLASTP、BLASTN和FASTA(Altschul，S.F.等人，J.Molec.Biol.，215:403-410(1990)。BLASTX程序可从NCBI和其它来源公开获得(BLASTManual，Altschul，S.等人，NCVI NLM NIH Bethesda，MD 20894，Altschul，S.F.等人，J.Molec.Biol.，215:403-410(1990)，其教导引入本文作为参考)。这些程序使用缺省的缺口权重来最佳比对序列，以便产生在给定序列和参考序列之间最高水平的序列相同性。作为说明，通过具有与参考核苷酸序列具有至少例如85％，优选90％，甚至更优选95％的“序列相同性”的核苷酸序列的多核苷酸，意指给定多核苷酸的核苷酸序列与参考序列相同，除了给定的多核苷酸序列可以包括高达15个，优选高达10个，甚至更优选高达5个点突变/参考核苷酸序列的每100个核苷酸之外。换言之，在具有相对于参考核苷酸序列具有至少85％，优选90％，甚至更优选95％相同性的核苷酸序列的多核苷酸中，参考序列中高达15％，优选10％，甚至更优选5％的核苷酸可以被缺失或被另一种核苷酸取代，或者参考序列中高达15％，优选10％，甚至更优选5％的总核苷酸的多个核苷酸可以被插入参考序列内。参考序列的这些突变可以在参考核苷酸序列的5'或3'末端位置处、或者在那些末端位置之间的任何位置处出现，或个别地散布在参考序列中的核苷酸中、或散布在参考序列内的一个或多个邻接基团中。类似地，通过具有与参考氨基酸序列具有至少例如85％，优选90％，甚至更优选95％的序列相同性的给定氨基酸序列的多肽，意指多肽的给定氨基酸序列与参考序列相同，除了给定的多肽序列可以包括高达15个，优选高达10个，甚至更优选高达5个氨基酸改变/参考氨基酸序列的每100个氨基酸之外。换言之，为了获得与参考氨基酸序列具有至少85％，优选90％，甚至更优选95％的序列相同性的给定多肽序列，参考序列中高达15％，优选高达10％，甚至更优选高达5％的氨基酸残基可以被缺失或被另一种氨基酸取代，或者参考序列中高达15％，优选高达10％，甚至更优选高达5％的氨基酸残基总数目的多个氨基酸可以被插入参考序列内。参考序列的这些改变可以在参考氨基酸序列的氨基或羧基末端位置处、或者在那些末端位置之间的任何位置处出现，或个别地散布在参考序列中的残基中、或散布在参考序列内的一个或多个邻接基团中。优选地，并不相同的残基位置通过保守氨基酸取代而不同。然而，当测定序列相同性时，保守取代不包括作为匹配。
术语“序列相同性”或“百分比相同性”在本文可互换使用。为了本发明的目的，在本文中定义，为了测定两个氨基酸序列或两个核酸序列的相同性百分比，序列为了最佳比较的目的进行比对(例如，可以在第一氨基酸或核酸序列中引入缺口，用于与第二氨基酸或核酸序列的最佳比对)。然后比较在相应的氨基酸或核苷酸位置处的氨基酸或核苷酸残基。当第一序列中的位置由与第二序列中的相应位置相同的氨基酸或核苷酸残基占据时，则分子在该位置处是相同的。两个序列之间的相同性百分比是由序列共享的相同位置数目的函数(即，％相同性＝相同位置数目/位置(即重叠位置)总数目x 100)。优选地，两个序列是相同长度的。
可以在待比较的两个序列的整个长度上或在两个序列的片段上进行序列比较。且在本发明的范围内通常且优选的，比较将在待比较的两个序列的全长上进行。然而，序列相同性可以在例如二十、五十、一百个或更多个邻接基酸残基的区域上进行。
如本文使用的，特别应理解，术语“与根据SEQ ID NO：Y的核酸/氨基酸序列具有至少X％的序列相同性”(或可替代地，术语“与SEQ ID NO：Y的/中所示的核酸/氨基酸序列具有至少X％的序列相同性”)分别等价于术语“在SEQ ID NO：Y的长度上，与根据SEQ ID NO：Y的核酸/氨基酸序列具有至少X％的序列相同性”、或术语“在SEQ ID NO：Y的整个长度上，与根据SEQ ID NO：Y的核酸/氨基酸序列具有至少X％的序列相同性”。
用于表达的载体以及用于制备和/或使用载体(或重组体)的方法可以通过以下中公开的方法或类似于以下中公开的方法：关于DNA病毒载体，尤其是美国专利号4,603,112、4,769,330、5,174,993、5,505,941、5,338,683、5,494,807、4,722,848、5,942,235、5,364,773、5,762,938、5,770,212、5,942,235、382,425，PCT公开WO 94/16716、WO96/39491、WO95/30018；Paoletti，"Applications of pox virus vectors to vaccination:Anupdate，"PNAS USA 93:11349-11353，1996年10月；Moss，"Genetically engineeredpoxviruses for recombinant gene expression，vaccination，and safety,"PNAS USA93:11341-11348，1996年10月；Smith等人，美国专利号4,745,051(重组杆状病毒)；Richardson，C.D.(编辑)，Methods in Molecular Biology 39，"Baculovirus ExpressionProtocols"(1995Humana Press Inc.)；Smith等人，"Production of Human BetaInterferon in Insect Cells Infected with a Baculovirus Expression Vector"，Molecular and Cellular Biology，1983年12月，第3卷，第12期，第2156-2165页；Pennock等人，"Strong and Regulated Expression of Escherichia coli B-Galactosidase inInfect Cells with a Baculovirus vector，"Molecular and Cellular Biology，1984年3月，第4卷，第3期，第406页；EPA0370 573；于1986年10月16日提交的美国申请号920,197；EP专利公开号265785；美国专利号4,769,331(重组疱疹病毒)；Roizman，"The function ofherpes simplex virus genes:A primer for genetic engineering of novelvectors,"PNAS USA 93:11307-11312，1996年10月；Andreansky等人，"The applicationof genetically engineered herpes simplex viruses to the treatment ofexperimental brain tumors,"PNAS USA 93:11313-11318，1996年10月；Robertson等人，"Epstein-Barr virus vectors for gene delivery to B lymphocytes"，PNAS USA 93:11334-11340，1996年10月；Frolov等人，"Alphavirus-based expression vectors:Strategies and applications,"PNAS USA 93:11371-11377，1996年10月；Kitson等人，J.Virol.65，3068-3075，1991；美国专利号5,591,439、5,552,143；WO 98/00166；两者均于1996年7月3日提交的批准的美国申请序列号08/675,556和08/675,566(重组腺病毒)；Grunhaus等人，1992，"Adenovirus as cloning vectors,"Seminars in Virology(第3卷)第237-52页，1993；Ballay等人EMBO Journal，第4卷，第3861-65页，Graham，Tibtech8，85-87，1990年4月；Prevec等人，J.Gen Virol.70，42434；PCT WO 91/11525；Felgner等人(1994)，J.Biol.Chem.269，2550-2561，Science，259:1745-49，1993；以及McClements等人，"Immunization with DNA vaccines encoding glycoprotein D or glycoprotein B，alone or in combination，induces protective immunity in animal models ofherpes simplex virus-2disease"，PNAS USA 93:11414-11420，1996年10月；以及美国专利号5,591,639、5,589,466和5,580,859，以及WO 90/11092、WO93/19183、WO94/21797、WO95/11307、WO95/20660；Tang等人，Nature，以及Furth等人，Analytical Biochemistry。还参见WO 98/33510；Ju等人，Diabetologia，41:736-739，1998(慢病毒表达系统)；Sanford等人，美国专利号4,945,050；Fischbach等人(Intracel)；WO 90/01543；Robinson等人，Seminars in Immunology第9卷，第271-283页(1997),(DNA载体系统)；Szoka等人，美国专利号4,394,448(将DNA插入活细胞内的方法)；McCormick等人，美国专利号5,677,178(致细胞病变病毒的使用)；以及美国专利号5,928,913(用于基因递送的载体)；以及本文引用的其它文件。
优选的病毒载体包括杆状病毒，例如BaculoGold(BD Biosciences Pharmingen，San Diego，Calif.)，特别条件是生产细胞是昆虫细胞。尽管杆状病毒表达系统是优选的，但本领域技术人员应理解，其它表达系统也可用于本发明的目的。
B.载体分子
本发明的SVA肽可以与之缀合或共价连接的载体分子优选是上文描述的那些。用于动物使用的优选载体是牛血清白蛋白和钥孔血蓝蛋白。适合于人使用的蛋白质载体包括破伤风类毒素、白喉类毒素、无细胞百日咳疫苗(LPF类毒素)、交叉反应材料(CRM)，其在抗原上与细菌毒素相似，但借助于突变而是无毒的。例如，可以使用根据Pappenheimer等人，Immunochemistry，9，891-906(1972)获得的CRM 197，以及其它细菌蛋白载体，例如脑膜炎球菌外膜蛋白。优选地，载体蛋白本身是免疫原。
本发明的SVA肽可以通过本领域已知的任何方便的方法共价偶联至载体。虽然如通过Schneerson等人，J.Experimental Medicine，152，361-376(1980)描述的对称接头例如己二酸二酰肼的使用，或如通过Fattom等人，Infection and Immunity，56，2292-2298(1988)描述的异双功能接头例如N-琥珀酰亚胺基3-(2-吡啶基二硫基)丙酸酯的使用在本发明的范围内，优选避免使用任何接头，而是将本发明的SVA肽直接偶联至载体分子。如通过Landi等人J.Immunology，127，1011-1019(1981)所述，可以借助于还原胺化来实现此类偶联。
如通过平均分子量定义的，免疫原性组合物的大小是可变的，并且取决于选择的SVA肽和SVA肽与载体的偶联方法。因此，它可以小至1,000道尔顿(103)或大于106道尔顿。用还原胺化偶联方法，SVA肽的分子量通常在5,000至500,000，例如300,000至500,000，或例如5,000至50,000道尔顿的范围内。
可以通过本领域已知的各种方法来产生特异性结合本发明的SVA肽的载体分子，即肽、其衍生物和类似物以及肽模拟物，所述方法包括但不限于固相合成或通过溶液(Nakanishi等人，1993，Gene 137:51-56；Merrifield，1963，J.Am.Chem.Soc.15:2149-2154；Neurath，H.等人，编辑，The Proteins，第II卷，第3版，第105-237页，AcademicPress，New York，N.Y.(1976)，其整体通过引用引入本文)。
本发明的SVA肽或者本发明的抗体或其结合部分可以通过在具有药学或兽医学载体的稀释剂中的溶液或悬浮液，以可注射剂量施用。
此类分子的毒性和治疗功效可以通过细胞培养或实验动物中，例如用于测定LD50(对50％的群体致死的剂量)的标准药学程序来测定。
本发明的疫苗可以是多价的或单价的。多价疫苗由多重SVA肽与载体分子的免疫缀合制成。
在一个方面，SVA肽组合物包含有效免疫量的免疫原性缀合物，优选与免疫刺激剂组合；以及生理学可接受的载体。如本上下文中使用的，“免疫刺激剂”预期涵盖具有增强免疫系统活性的能力的任何化合物或组合物，无论它是与特定抗原组合的特异性增强效应，还是简单地对免疫应答的一种或多种元件的活性的独立效应。免疫刺激剂化合物包括但不限于矿物质凝胶，例如氢氧化铝；表面活性物质，如溶血卵磷脂，
Figure BDA0002360499750000171
多元醇；聚阴离子；肽；油乳液；明矾和MDP。利用这些材料的方法是本领域已知的，并且对于给定疫苗测定刺激剂的最佳量在技术人员的能力内。在给定的制剂中可以使用超过一种免疫刺激剂。免疫原也可以掺入脂质体内，或者与多糖和/或其它聚合物缀合用于在疫苗制剂中使用。
需要时，组合物可以存在于包装或分配器装置中，其可以包含含有活性成分的一种或多种单位剂型。包装可以例如包含金属或塑料箔，如泡罩包装。包装或分配器装置可以伴随有施用说明书，优选用于施用于哺乳动物，尤其是猪。与此类容器相关的可以是以由管理药物或生物制品制造、使用或销售的政府机构规定形式的通知，所述通知反映了由制造、使用或销售机构批准用于人施用。
C.佐剂
为了进一步增加本文提供的并且含有一种或多种SVA肽的免疫原性组合物的免疫原性，还可以包含一种或多种佐剂。
佐剂可以通过先前描述的或本领域已知的任何技术来纯化。优选的纯化技术是硅胶色谱，特别是“闪速”(快速)色谱技术，如通过W.Clark Still等人，J.OrganicChemistry，43，2923-2925(1978)所述。然而，其它色谱方法，包括HPLC，也可以用于佐剂的纯化。结晶也可以用于纯化佐剂。在一些情况下，不需要纯化，因为直接从合成获得分析纯度的产物。
通过根据已知技术在适当的无菌条件下，将佐剂与SVA肽物理混合以产生佐剂化组合物，来制备本发明的疫苗组合物。SVA肽与佐剂的络合通过在缀合物上净负电荷的存在得到促进，所述净负电荷被静电吸引至长链烷基化合物佐剂上存在的正电荷。
预期可以以约100μg至约10mg/剂的量，优选以约100μg至约10mg/剂的量，更优选以约500μg至约5mg/剂，甚至更优选以约750μg至约2.5mg/剂的量，且最优选以约1mg/剂的量添加佐剂。可替代地，佐剂可以为按最终产物的体积计约0.01％至75％的浓度，优选为约2％至30％的浓度，更优选为约5％至25％的浓度，还更优选为约7％至22％的浓度，且最优选为10％至20％的浓度。
D.生理学可接受的媒介物
本发明的疫苗组合物可以使用类似于用于其它药物多肽组合物的技术进行配制。因此，佐剂以及优选与载体分子缀合和/或与佐剂混合的SVA肽可以以冻干形式贮存，并且在施用前在生理学可接受的媒介物中重构以形成悬浮液。可替代地，佐剂和缀合物可以贮存于媒介物中。优选的媒介物是无菌溶液，特别是无菌缓冲溶液，例如磷酸盐缓冲盐水。将佐剂和缀合物在媒介物中组合使得改善免疫原性组合物的免疫学有效性的任何方法都是适当的。
本发明的疫苗的单一剂量的体积可以变化，但一般在常规疫苗中通常采用的范围内。在上述缀合物和佐剂的浓度下，单一剂量的体积优选在约0.1ml至约3ml之间，优选在约0.2ml至约1.5ml之间，更优选在约0.2ml至约0.5ml之间。
本发明的疫苗组合物可以通过任何方便的手段施用。
E.制剂
包含与载体分子偶联的SVA肽的免疫原性缀合物可以用作用于针对SVA免疫的疫苗。包含在生理学可接受的媒介物中的免疫原性缀合物的疫苗可用于免疫动物，优选猪的方法中，用于治疗或预防通过SVA的感染。
通过用免疫原性缀合物免疫而生成的针对本发明的免疫原性缀合物的抗体可以用于被动免疫疗法和生成用于治疗或预防SVA感染的抗独特型抗体。
组合物施用于其的对象优选是动物，包括但不限于牛、马、绵羊、猪、家禽(例如鸡)、山羊、猫、犬、仓鼠、小鼠和大鼠，最优选地哺乳动物是猪。
本发明的制剂包含有效免疫量的一种或多种免疫原性组合物或针对其的抗体和生理学可接受的媒介物。疫苗包含有效免疫量的一种或多种免疫原性组合物和生理学可接受的媒介物。该制剂应该适合施用模式。
需要时，免疫原性组合物还可以含有少量的润湿剂或乳化剂或pH缓冲剂。免疫原性组合物可以是液体溶液、悬浮液、乳剂、片剂、丸剂、胶囊、缓释制剂或粉末。经口制剂可以包括标准载体，例如药物级别的甘露醇、乳糖、淀粉、硬脂酸镁、糖精钠、纤维素、碳酸镁等。
F.有效剂量
本文所述的化合物可以以治疗有效剂量施用于对象，以治疗SVA相关的疾病。剂量将取决于接受疫苗的宿主，以及诸如宿主的大小、重量和年龄等因素。
待在制剂中采用的本发明的免疫原性缀合物或抗体的精确量取决于施用途径和对象的性质(例如，物种、年龄、大小、疾病的阶段/水平)，并且应该根据从业者的判断和每个对象的情况根据标准临床技术来决定。有效免疫量是足以治疗或预防对象中的SVA传染病的量。适当剂量的实例是约6至7log TCID50/mL。可替代地，有效剂量也可以从衍生自动物模型测试系统的剂量应答曲线外推，并且可以从0.001mg/kg到100mg/kg不等。
化合物的毒性和治疗功效可以通过细胞培养或实验动物中，例如用于测定LD50(对50％的群体致死的剂量)和ED50(在50％的群体中治疗有效的剂量)的标准药学程序来测定。毒性和疗效之间的剂量比是治疗指数，并且它可以表示为比率LD50/ED50。显示出大治疗指数的化合物是优选的。虽然可以使用显示出毒性副作用的化合物，但应该小心设计将此类化合物靶向受影响组织的部位的递送系统，以便最小化对未感染细胞的潜在损害，且从而减少副作用。
从细胞培养测定和动物研究中获得的数据可以用于制定用于在动物，尤其是猪中使用的剂量范围。此类化合物的剂量优选位于循环浓度的范围内，所述循环浓度包括具有很少毒性或没有毒性的ED50。剂量可以在这个范围内变化，取决于所采用的剂型和所利用的施用途径。对于本发明的方法中使用的任何化合物，治疗有效剂量可以最初由细胞培养测定估计。剂量可以在动物模型中制定，以达到包括如在细胞培养中测定的IC50(即，达到症状的半最大抑制的测试化合物浓度)的循环血浆浓度范围。此类信息可以用于更准确地测定在对象中的有用剂量。血浆中的水平可以例如通过高效液相色谱进行测量。
组合物的免疫原性可以通过使用本领域已知的任何免疫测定，监测在用组合物免疫后的测试对象的免疫应答来测定。体液(抗体)应答和/或细胞介导的免疫的生成可以视为免疫应答的指示。测试对象可以包括动物，例如猪、小鼠、仓鼠、犬、猫、兔、牛、马、羊、家禽(例如鸡、鸭、鹅和火鸡)。
可以通过各种方法来分析测试对象的免疫应答，所述方法例如：如通过已知技术例如酶联免疫吸附测定(ELISA)、免疫印迹、免疫沉淀等测定的，所得的免疫血清对免疫原性缀合物的反应性；或者通过保护免疫宿主免于通过病原体的感染和/或减弱免疫宿主中由于通过病原体感染的症状，如通过本领域已知用于测定传染病原的水平，例如细菌水平(例如，通过培养来自对象的样品)的任何方法，或本领域已知的其它技术测定的。传染病原的水平也可以通过测量免疫球蛋白针对其的抗原的水平来测定。传染病原的水平中的降低或传染病症状的改善指示该组合物是有效的。
在体内用于动物或人之前，本发明的治疗剂可以在体外测试所需治疗或预防活性。例如，可以用于测定是否指示特定治疗剂的施用的体外测定包括体外细胞培养测定，其中来自细胞系的适当细胞或者从患有特定疾病或病症的对象培养的细胞暴露于或以其它方式施用治疗剂，并且观察到治疗剂对细胞的作用。
可替代地，治疗剂可以通过以下进行测定：使治疗剂与易受传染病原感染但未被传染病原感染的细胞(从对象培养或培养的细胞系培养)接触，使细胞暴露于传染病原，然后测定与治疗剂接触的细胞的感染率是否低于未与治疗剂接触的细胞的感染率。可以通过本领域已知的任何方法来测定细胞被传染病原的感染。
另外，可以通过在治疗之前、过程中或之后的合适时间间隔，测量动物模型或人对象中抗体针对其的分子水平来评价治疗剂。可以鉴定分子的量中的任何变化或变化的不存在，并且与治疗对对象的作用相关联。分子的水平可以通过本领域已知的任何方法测定。
使用本发明的方法和组合物使动物对SVA感染疫苗接种后，本领域已知的任何结合测定可以用于评价所得到的抗体与特定分子之间的结合。也可以进行这些测定，以选择对于特定抗原显示出更高亲和力或特异性的抗体。
G.检测和诊断方法
起因于本发明的SVA肽的使用的抗体或其结合部分可用于检测样品中SVA病毒的存在。这种检测方法包括以下步骤：提供针对本发明的SVA肽的分离的抗体或其结合部分，向分离的抗体或其结合部分中加入怀疑含有一定数量的SVA的样品，并且检测包含与SVA结合的分离的抗体或其结合部分的复合物的存在。
本发明的抗体或其结合部分也可用于检测样品中SVA肽的存在。这种检测方法包括以下步骤：提供针对SVA肽的分离的抗体或其结合部分，向分离的抗体或其结合部分中加入怀疑含有一定数量的SVA肽的样品，并且检测包含与SVA肽结合的分离的抗体或其结合部分的复合物的存在。
如本文所述，结合其为结合对成员的特定分子的免疫球蛋白，特别是抗体(及其功能活性片段)可以用作诊断剂和预后剂。在各种实施方案中，本发明提供了结合对成员的测量，以及此类测量在临床应用中的用途。本发明中的免疫球蛋白可以用于例如检测生物样品中的抗原，由此可以测试对象的免疫球蛋白与之结合的分子的异常水平、和/或此类分子的异常形式的存在。“异常水平”意指相对于来自身体的一部分或没有疾病的对象的类似样品中存在的水平、或者代表其的标准水平的增加或降低。本发明的抗体也可以作为试剂包括在用于诊断或预后技术的试剂盒中。
在一个方面，与SVA肽免疫特异性结合的本发明的抗体可以用于诊断、预后或筛查SVA感染。
在另一个方面，本发明提供了诊断或筛选SVA感染或针对其的免疫的存在的方法，其包括在其中所述抗体免疫特异性结合SVA肽的对象中，测量抗体与衍生自对象的样品的免疫特异性结合的水平，其中相对于来自没有传染病原的对象的类似样品中的所述免疫特异性结合的水平，所述免疫特异性结合的水平中的增加指示SVA的存在。
检测SVA肽或其拮抗剂的存在的合适测定的实例包括但不限于ELISA、放射免疫测定、凝胶扩散沉淀反应测定、免疫扩散测定、凝集测定、荧光免疫测定、蛋白A免疫测定或免疫电泳测定。
用于特定分子的免疫测定通常包括在可检测地标记的抗体的存在下，温育样品，例如生物流体、组织提取物、新鲜收获的细胞或培养的细胞的裂解产物，并且通过本领域众所周知的许多技术中的任一种检测结合的抗体。
可以根据众所周知的方法测定给定抗体的结合活性。本领域技术人员能够通过采用常规实验来测定用于每次测定的操作和最佳测定条件。
本发明的另一个方面涉及用于检测或测量SVA的诊断试剂盒。提供了用于诊断用途的试剂盒，其包含在一个或多个容器中的抗SVA肽抗体，以及任选地与该抗体的标记的结合配偶体。可替代地，抗SVA肽抗体可以是被标记的(用可检测的标记物，例如化学发光、酶促、荧光或放射性部分)。相应地，本发明提供了诊断试剂盒，其包含抗SVA肽抗体和对照免疫球蛋白。在一个具体实施方案中，容器的前述化合物之一可以进行可检测地标记。试剂盒可以任选地进一步包含在容器中的预定量的由试剂盒的抗体识别的SVA肽，用于用作标准或对照。
优选的施用途径包括但不限于鼻内、经口、皮内和肌内。经由肌内途径，最优选在单一剂量中的施用是期望的。本领域技术人员将认识到，本发明的组合物也可以在两个或更多个剂量中，以及通过其它施用途径来施用。例如，此类其它途径包括皮下、皮内、静脉内、血管内、动脉内、腹膜内、鞘内、气管内、皮内、心内、叶内、髓内、肺内和阴道内。取决于治疗的所需持续时间和有效性，本发明的组合物可以一次或几次，以及间歇地施用，例如在每天一次的基础上共几天、几周或几个月，并且以不同的剂量。
包括下述实施例以证实本发明的优选实施方案。本领域技术人员应该了解，下述实施例中公开的技术代表由发明人发现的在本发明的实践中发挥良好作用的技术，且因此可以视为构成用于其实践的优选模式。然而，根据本公开内容，本领域技术人员应了解，可以在所公开的特定实施例中进行许多改变，并且仍获得同样或相似的结果，而不脱离本发明的精神和范围。
序列表
本申请含有序列表。序列表包括下述序列：
SEQ ID NO：1表示本发明的SVA毒株的接近完整的基因组的RNA序列。
SEQ ID NO：2表示编码病毒多蛋白(SVV抗原；SEQ ID NO：3)的基因组RNA序列的子集。
SEQ ID NO：3表示由SEQ ID NO：2编码的病毒多蛋白(SVV抗原)的氨基酸序列。
SEQ ID NO：4表示GenBank_KX377924。
SEQ ID NO：5表示GenBank_KT321458。
SEQ ID NO：6表示GenBank_KR063107。
SEQ ID NO：7表示GenBank_KR063108。
SEQ ID NO：8表示GenBank_KR063109。
SEQ ID NO：9表示GenBank_HJ999048。
SEQ ID NO：10表示GenBank_KC667560。
SEQ ID NO：11表示GenBank_GY488390。
SEQ ID NO：12表示GenBank_GV614995。
SEQ ID NO：13表示GenBank_DM060849。
SEQ ID NO：14表示GenBank_NC_011349。
SEQ ID NO：15表示GenBank_GY488390_CDS。
SEQ ID NO：16表示GenBank_GV614995_CDS。
SEQ ID NO：17表示GenBank_DM060849_CDS。
SEQ ID NO：18表示构建体BaculoFBU/SVVP13C(A)中的SVVP13C插入的核苷酸序列。
SEQ ID NO：19表示从BaculoFBU/SVVP13C表达的SVVP13C多蛋白的氨基酸序列。
SEQ ID NO：20表示构建体BaculoFBU/SVVP13C-CO中的SVVP13C插入的核苷酸序列，其中SVV P1区进行密码子优化用于在昆虫细胞中表达(B)。
SEQ ID NO：21表示从BaculoFBU/SVVP13C-CO表达的SVVP13C多蛋白的氨基酸序列。
SEQ ID NO：22表示BaculoFBU/VVP13C VP3/VP1。
SEQ ID NO：23表示构建体BaculoFBU/SVVP13C VP3/VP1的SVVP13C VP3/VP1插入的核酸序列。
SEQ ID NO：24表示构建体BaculoFBU/SVVP13CD的SVVP13CD插入的核酸序列。
SEQ ID NO：25表示从BaculoFBU/SVVP13CD表达的SVVP13CD多蛋白的氨基酸序列。
SEQ ID NO：26表示含有关于SVVP1-His的编码序列的PCR产物的核酸序列。
SEQ ID NO：27表示从构建体BaculoG/SVVP1-His-sIRES-SVV3C表达的SVVP1-His的氨基酸序列。
SEQ ID NO：28表示含有关于SVVP1-His的编码序列的PCR产物的核酸序列，所述编码序列已进行密码子优化用于在昆虫细胞中表达(SVVP1CO-His)。
SEQ ID NO：29表示从构建体BaculoG/SVVP1CO-His-sIRES-SVV3C表达的SVVP1-His的氨基酸序列。
SEQ ID NO：30表示含有关于SVV3C的编码序列的PCR产物的核酸序列。
SEQ ID NO：31表示从构建体BaculoG/SVVP1-His-sIRES-SVV3C和BaculoG/SVVP1CO-His-sIRES-SVV3C表达的SVV3C的氨基酸序列。
SEQ ID NO：32表示pORB-SVVP1-His-sIRES-SVV3C中的SVVP1-His-sIRES-SVV3C表达盒的核酸序列。
SEQ ID NO：33表示pORB-SVVP1CO-His-sIRES-SVV3C中的SVVP1CO-His-sIRES-SVV3C表达盒的核酸序列。
SEQ ID NO：34表示PCR引物P3219012A(SVVP1正向)。
SEQ ID NO：35表示PCR引物P3219039A(SVVP1 His反向)。
SEQ ID NO：36表示PCR引物P3219012C(SVVP1-CO正向)。
SEQ ID NO：37表示PCR引物P3219039B(SVVP1-CO His反向)。
SEQ ID NO：38表示PCR引物P3219012E(SVV3C正向)。
SEQ ID NO：39表示PCR引物P3219039C(SVV3C反向)。
SEQ ID NO：40表示PCR引物P3219165A(VP3/VP1正向)。
SEQ ID NO：41表示PCR引物P3219165B(VP3/VP1反向)。
SEQ ID NO：42表示PCR引物P3219166A(SVV3D正向)。
SEQ ID NO：43表示PCR引物P3219166B(SVV3C反向)。
SEQ ID NO：44表示PCR引物P3219166C(SVV3D反向)。
SEQ ID NO：45表示SVV3D编码序列。
本发明进一步包括下述条款：
1.一种在哺乳动物中生成免疫应答的方法，其包括施用免疫学有效量的杀死的塞内卡谷病毒A(SVA)，其包含：
(a)SEQ ID NO：1或SEQ ID NO：2的核酸序列，或
(b)与SEQ ID NO：1 97％相同的核酸序列，其编码具有SEQ ID NO：3的多肽的免疫学有效活性的多肽。
2.一种在哺乳动物中生成免疫应答的方法，其包括施用免疫学有效量的杀死的SVA，其包含：
(a)具有SEQ ID NO：3的氨基酸序列；
(b)具有与SEQ ID NO：3 80％相同的氨基酸序列，并且具有由SEQ ID NO：3编码的多肽的生物学或免疫学有效活性；或
(c)其为SEQ ID NO：3的氨基酸序列的片段，其包含SEQ ID NO：3的至少15个邻接氨基酸并且具有免疫学有效活性。
3.一种在哺乳动物中生成免疫应答的方法，其包括施用免疫学有效量的杀死的SVA，其包含：
(a)SEQ ID NO：1或SEQ ID NO：2的核酸序列，或
(b)与SEQ ID NO：1或SEQ ID NO：2 97％相同的核酸序列，其编码具有SEQ ID NO：3的多肽的免疫学有效活性的多肽。
4.一种在哺乳动物中生成免疫应答的方法，其包括施用免疫有效量的根据条款1的免疫原性组合物。
5.一种在哺乳动物中生成免疫应答的方法，其包括施用免疫有效量的根据条款2的免疫原性组合物。
6.一种在哺乳动物中生成免疫应答的方法，其包括施用免疫有效量的根据条款3的免疫原性组合物。
7.根据条款1的方法，其中所述哺乳动物是猪，并且所述免疫应答提供对由SVA感染引起的疾病的保护性免疫。
8.根据条款2的方法，其中所述哺乳动物是猪，并且所述免疫应答提供对由SVA感染引起的疾病的保护性免疫。
9.根据条款3的方法，其中所述哺乳动物是猪，并且所述免疫应答提供对由SVA感染引起的疾病的保护性免疫。
10.一种疫苗，其包含塞内卡病毒A(SVA)的一种或多种抗原，其中所述SVA是包含以下的任何SVA：
(a)由SEQ ID NO：1编码，和/或包含SEQ ID NO：1的序列和/或包含SEQ ID NO：1的RNA等价物的核酸；
(b)其序列与SEQ ID NO：1至少99％相同和/或与SEQ ID NO：1的RNA等价物至少99％相同的核酸；
(c)由包含SEQ ID NO：1或2的序列的多核苷酸编码的多肽；
(d)由与a)的多核苷酸至少80％同源或相同的多核苷酸编码的多肽；
(e)由多核苷酸编码的蛋白质片段，所述多核苷酸包含SEQ ID NO：1或SEQ ID NO：2的序列中包括的至少15个，优选24个，更优选30个，甚至更优选45个邻接核苷酸；
(f)包含SEQ ID NO：3的氨基酸序列的多肽；
(g)与f)的多肽至少80％同源和/或相同的多肽；
(h)f)和/或g)的多肽的片段；
(i)f)或g)的多肽；或
(j)h)或i)的片段，其包含SEQ ID NO：3的序列中包括的至少5个，优选8个，更优选10个，甚至更优选15个邻接氨基酸。
11.条款10的疫苗，其中所述疫苗是重组疫苗或杀死的疫苗。
12.条款10的疫苗，其中所述疫苗是杀死的疫苗。
13.条款10的疫苗，其中所述塞内卡病毒A(SVA)是化学灭活的。
14.条款13的疫苗，其中所述塞内卡病毒A(SVA)通过用化学灭活剂处理进行化学灭活，所述化学灭活剂包括选自乙烯亚胺、二元乙烯亚胺、乙酰乙烯亚胺及其混合物的化合物。
15.条款14的疫苗，其中所述塞内卡病毒A(SVA)通过用二元乙烯亚胺处理进行化学灭活。
16.条款10的疫苗，其中所述疫苗进一步包含佐剂。
17.条款16的疫苗，其中所述佐剂是
Figure BDA0002360499750000251
基于水包油型乳液的佐剂。
18.条款6的疫苗，其中所述塞内卡病毒A(SVA)包含SEQ ID NO：1，和/或包含SEQID NO：1的RNA等价物。
19.条款11的疫苗，其中所述疫苗是重组疫苗。
20.条款11的疫苗，其中此类重组疫苗包含选自以下的一种或多种免疫原性组分：
(a)编码塞内卡病毒A(SVA)抗原的分离的核酸，其中所述重组多肽与SEQ ID NO：3具有至少90％的同源性，
(b)包含a)的分离的核酸的载体，
(c)由a)的核酸编码的重组蛋白，和
(d)其任何组合。
21.条款20的疫苗，其中此类疫苗包含药学可接受的载体和/或赋形剂。
22.条款21的疫苗，其中所述赋形剂是一种或多种佐剂。
23.条款22的疫苗，其中所述佐剂是
Figure BDA0002360499750000252
基于水包油型乳液的佐剂。
24.条款20的疫苗，其中所述疫苗进一步包含一种或多种另外的抗原。
25.条款20的疫苗，其中免疫原性组分是分离的核酸。
26.条款20的疫苗，其中免疫原性组分是载体。
27.条款11的疫苗，其中免疫原性组分是重组塞内卡病毒A(SVA)P1蛋白。
28.条款20的疫苗，其中免疫原性组分是组合。
实施例
实施例1
这项研究利用常规动物来测定疫苗施用后的血清学应答诱导的初步可行性。这项研究的主要目的是评估使用塞内卡病毒A(SVA)(SEQ ID NO：1或SEQ ID NO：2，和/或与SEQID NO：1 97％相同的核酸序列，其编码具有SEQ ID NO：3的多肽的免疫学有效活性的多肽)的灭活的全病毒制剂，在常规猪中是否血清转化为SVA疫苗。
对于病毒分离，通过0.2/0.8μm注射器式滤器(Pall Acrodisc目录4658)过滤0.5mL水泡液，并且将滤液用于接种到猪睾丸细胞(ST细胞)上。ST细胞在6孔板中生长至80-100％融合。抽吸培养基，并且将0.25mL滤液接种到细胞上。在37℃下的一小时吸附后，将简单的无血清培养基加入细胞中。使板在37℃、5％CO2大气下温育，并且每天检查致细胞病变效应(CPE)。CPE通常在24-28小时内完成。收获的病毒传代几次且用于生成系列。
通过用5mL病毒原液和160mL培养基(最低基础培养基+2.5％HEPES)接种用AI-ST细胞种植的烧瓶来制备病毒原液。使烧瓶温育大约48小时。将烧瓶冷冻，然后在室温下解冻。材料进行0.2μm过滤。用10mM BEI和0.2％甲醛的组合来灭活病毒，伴随在37℃下72小时的恒定搅动。用硫代硫酸钠(添加了17％的BEI体积)和亚硫酸氢钠中和灭活。灭活通过材料在AI-ST细胞上的两次传代加以确认。对于最初的传代，将10mL灭活的材料接种到AI-ST细胞的T75烧瓶上。使烧瓶在37℃+5％CO2下温育7天，并且定期评估致细胞病变效应的存在。对于第二次传代，将烧瓶冷冻，然后解冻。将材料离心并且将10mL上清液接种到AI-ST细胞的T75烧瓶上。使烧瓶在37℃+5％CO2下温育7天，并且定期评估致细胞病变效应的存在。测定中包括阳性和阴性对照样品。结果确认这两个批次中的生长缺乏。使用10k，650cm2超滤中空纤维药液筒，将灭活的病毒收获物浓缩至12.4x。将浓缩的系列与
Figure BDA0002360499750000263
D(从Phibro Animal Health Corporation商购可得)进行无菌组合，以实现12.5％的制剂。将混合物在室温下搅拌30分钟，然后无菌分配到30mL疫苗瓶内，并且贮存于4℃下。通过在血琼脂平板上在37℃下48小时的常规培养(厌氧和好氧)，测试材料的细菌无菌性。未检测到细菌污染。
如表1中所示，将二十头猪随机分成两组。关于组的描述和住房结构，参见下表1。在D0时，向猪施用2mL肌内剂量的SVA疫苗或安慰剂。在第21时，动物接受SVA疫苗或安慰剂的加强施用。在每次疫苗接种(D0和D21)和D35时的治疗施用之前，从所有猪中收集血液。就血清转化为SVA的证据测定血清样品的子集。在研究自始至终记录一般健康观察。在疫苗施用后观察注射部位的反应最少三天。在试验结束时对动物实施人道安乐死。
表1：研究设计
Figure BDA0002360499750000261
这项研究证实，在施用两个剂量的用12.5％
Figure BDA0002360499750000262
D佐剂化的BEI灭活的SVA原型后，对SVA的100％血清转化(如通过病毒中和测量的)。关于关键事件和样品收集的时间表参见表2。
表2.关键事件和样品收集的时间表
Figure BDA0002360499750000271
*注意观察持续直到反应消退
为了避免偏差，通过不涉及动物临床监测的人员在D0和D21时施用治疗。在D0时，使用适当大小的无菌针头和注射器，将2mL剂量的疫苗施用于健康猪的右颈部的肌肉组织内。在D21时，该过程相同，除了注射在颈部的左侧给予之外。在疫苗剂量确认记录(VaccineDose Confirmation Record)上，记录批号、剂量的量、动物标识号和疫苗材料的施用时机。
在疫苗接种期过程中，每天使用一般健康观察表对动物进行评估。具体地，如果所有动物都是正常的，则对于状态输入N。如果发现异常猪，则对于状态输入A，并且列出具体动物标识号和异常。每次疫苗接种后，监测注射部位区域的发红、肿胀、发热和疼痛的存在(或存在或不存在)和大小(cm)至少三天。如果病变显而易见，则监测它们直至消退。
在血液收集日，使用适当大小的
Figure BDA0002360499750000272
针、
Figure BDA0002360499750000273
持针器(两者均从Becton Dickinson and Company Corporation商购可得)和适当大小的血清分离管(SST)，通过研究人员或指定人员经由前腔静脉从每头猪中收集3至8mL静脉全血。
将血清样品保持在2-8℃下直至测试。加工在收到后48小时内完成。血液管在4℃下以1960x g离心10分钟。血清通过离心与凝块分开，并且倾析到两个螺旋盖低温小瓶内，所述小瓶标有至少研究编号、研究日和动物ID。等分试样贮存于-70℃±10℃下。在这项研究完成后，样品贮存最少六个月。
使用SVA分离株NAC#20150909，通过病毒中和测定来测试选择的血清样品。
在测试结束时，将动物深度麻醉，并且从每只动物中收集1x 250mL离心瓶的血液。对动物实施安乐死并且触诊注射部位。所有动物都按照AUP和设施标准操作程序进行饲养。
猪被视为实验单位。母猪编号9、116、787和895(n＝30)出生的以及来自母猪编号141和145(n＝6)的可用猪列表用于随机化。具体地，对猪分配随机编号(使用random.org)。猪按母猪分类，然后为随机编号。围栏分配被分配随机编号(使用random.org)。然后将围栏分配按随机编号分类，并且与动物列表组合。
统计分析和数据概括由研究监测仪进行。所有数据都输入
Figure BDA0002360499750000282
版本11.1.1内用于分析。生成按治疗组的数据列表和概括统计学。
内部开发的病毒中和测定用于测量疫苗接种后动物中的血清转化。在疫苗接种之前，没有动物具有可检测的血清学应答。到D35时，所有接种疫苗的动物(组1)都具有可检测的应答。该测定以1:80的稀释度运行，并且将动物视为阳性或阴性。关于SVA VN结果的概括，参见下表3。
表3：按组和研究日的SVA VN结果
Figure BDA0002360499750000281
这项研究的主要目的是评估在用SVA疫苗的疫苗接种后，常规猪是否血清转化为SVA。
关于SVA疫苗，用灭活的SVA原型疫苗接种疫苗的100％猪能够生成中和抗体应答。总之，这项研究能够证实原型灭活SVA疫苗的功效的合理预期。
实施例2
在pUCIDT-Amp载体(Integrated DNA Technologies)中排序了两个基因序列。SVVP13C基因(SEQ ID NO：18)是全长P1多蛋白的天然序列，具有连接P1多蛋白和3C自切割蛋白酶的2A以及部分2B和3B序列。SVVP13C-CO基因(SEQ ID NO：20)是SVVP13C的昆虫密码子优化版本，其中P1、2A和2B序列具有使用IDT密码子优化工具(IDT Codon OptimizationTool)进行密码子优化，而3B和3C保留为天然序列。这两个基因均具有在起始密码子之前的Kozak序列，以及分别在5'和3'末端处的BamHI和NotI限制性位点。SVVP13C(SEQ ID NO：18)和SVVP13C-CO(SEQ ID NO：20)插入片段分别通过BamHI和NotI消化从pUCIDT-AMP-SVVP13C和pUCIDT-AMP-SVVP13C-CO质粒中切下，并且连接到pVL1393载体(BD Biosciences)内。关于天然和密码子优化的pVL1393构建体的构建体设计，参见图1。
使用在每个基因的3'末端上添加关于6X His标签的编码序列的引物(SEQ ID NO：34、35、36和37)进行PCR扩增，以分别从pIDT-AMP-SVVP13C和pIDT-AMP-SVVP13C-CO扩增SVVP1-His(SEQ ID NO：26)和SVVP1CO-His(SEQ ID NO：27)序列。使用引物从pIDT-AMP-SVVP13C扩增SVV3C序列(SEQ ID NO：30)，以添加5’SpeI位点和3’SacI位点(SEQ ID：38和39)。(关于引物见表4)。
表4.关于SVVP1-His-SVV3C和SVVP1CO-His-SVV3C的引物序列
Figure BDA0002360499750000291
表5.关于SVVP13C VP3/VP1和SVVP13CD的引物序列
Figure BDA0002360499750000292
使用SpeI和SacI限制性位点，将SVV3C插入片段(SEQ ID NO：30)连接到pORB-MCS1-sIRES-MCS2载体(Allele Biotechnology)的第二个多克隆位点(MCS2)内。随后，利用BamHI和NotI限制性位点，将SVVP1-His或SVVP1CO-His连接到pORB-MCS1-sIRES-SVV3C的MCS1内，以分别生成pORB-SVVP1-His-sIRES-SVV3C(SEQ ID NO：32)和pORB-SVVP1CO-His-sIRES-SVV3C(SEQ ID NO：33)。
引物设计为使pUCIDT-AMP-SVVP13C中的SVVP13C序列(SEQ ID NO：18)的VP3/VP1切割位点(核苷酸1786-1797)从FH/ST突变为PQ/GV(关于引物参见上表5，SEQ ID NO：40和41)，使用Lightning Quik Site Directed Mutagenesis试剂盒(Stratagene)。突变的序列，SVVP13C VP3/VP1(SEQ ID NO：22)从pUCIDT-AMP-SVVP13C VP3/VP1中切下，并且连接到pVL1393载体内，以产生pVL1393-SVVP13C VP3/VP1。使用重叠引物组(SEQ ID NO：34、42、43和44)，通过重叠延伸PCR(OE-PCR)，另外的构建体将SVV3D编码序列(SEQ ID NO:45)与SVVP13C序列(SEQ ID NO：18)的3'末端融合。使用BamHI和NotI限制性位点，将所得到的PCR产物SVVP13CD(SEQ ID NO：24)克隆到pVL1393内。(关于SVVP13C VP3/VP1(SEQ ID NO：22)和SVVP13CD构建体(SEQ ID NO：24)的图解，参见图3)。
根据制造商的说明书，使用ESCORT转染试剂(Sigma Aldrich)，将基于pVL1393的质粒中的重组SVV衣壳构建体与FlashBAC ULTRA(FBU)杆状病毒DNA(Oxford ExpressionTechnologies)一起共转染到Sf9细胞内，而将基于pORB的质粒与BaculoGold杆状病毒DNA(BD Biosciences)一起共转染到Sf9昆虫细胞内。收获来自转染的Sf9细胞的细胞培养上清液，并且以1,000xg离心5分钟进行澄清，以使细胞碎片形成团块。收集澄清的上清液，进行0.2μM过滤，并且作为P1转染收获物贮存。Sf9昆虫细胞用于生成P2原液，然后P2原液用于生成SVV构建体的P3和P4扩增，用于SF+昆虫细胞中的蛋白质表达评估。收获杆状病毒感染的SF+细胞，并且在4℃下以10,000xg的速率澄清10分钟。每天取样杆状病毒感染的SF+细胞的培养物，以通过Vi-Cell分析监测总细胞/mL、活细胞/mL、活力百分比和细胞直径。当活力≤30％活力或活细胞≤1x106个细胞/mL时，收获扩增。每天收集另外1mL样品，以评估随着感染进展的蛋白质表达，并且如上所述进行加工。将收集的上清液和细胞团块样品贮存在-70℃下直至评估。
裂解昆虫细胞团块以分开可溶性和不溶性级分
将SF+昆虫细胞培养物样品离心，以使细胞形成团块，这之后去除培养基，并且将细胞团块冷冻直至裂解。将团块重悬浮于含有下述的裂解缓冲液中：在去离子水中的20mMTris、1％Triton X-100、用于加上His标签的蛋白质的蛋白酶抑制剂混合物(10μL/mL)和Benzonase(250单位/mL)，其中pH为7.4。将重悬浮的昆虫细胞裂解产物涡旋10秒，在室温下温育5分钟，再次涡旋10秒，然后在4℃下以19,090xg离心10分钟，以使不溶性材料形成团块。将可溶性裂解产物吸取离开不溶性级分，并且在-70℃下贮存于管中。
SVV重组衣壳蛋白的纯化
将含有表达的重组SVV衣壳蛋白的上清液收获物进行0.2μM过滤，分配到超速离心管内，并且在4℃下以100,000xg离心2小时，以使蛋白质和可能的VLP形成团块。小心倾析澄清的上清液，然后将形成团块的材料重悬浮于TBS中，并且贮存于4℃下。不连续的10％-60％蔗糖梯度用于进一步纯化关于分别构建体的重组SVV衣壳蛋白。将分别重悬浮的材料加入梯度的顶部，并且在4℃下以100,000xg离心2小时。将来自蔗糖梯度的级分平均收集到管内(其中级分1从梯度表面的顶部开始)，并且贮存于4℃。
SDS-PAGE和蛋白质
使用NuPAGE电泳系统和4-12％Bis-Tris MES微型凝胶进行SDS-PAGE。在还原条件下，使用0.05M DTT，在175V下适当的时间来分开样品。凝胶使用eStain 2.0ProteinStaining Device就总蛋白质进行染色，或使用iBlot系统转移到硝酸纤维素膜用于蛋白质印迹。，通过Snap ID Protein Detection System(EMD Millipore)，利用在抗体稀释物中的阴性对照杆状病毒抗原，用抗SVV肽兔多克隆抗体(抗VP1-2、抗VP2-2和抗VP3-1，不同稀释度)和山羊抗兔过氧化物酶标记的二抗(1：500)进行蛋白质印迹，并且使用TMB膜过氧化物酶底物显色。
纯化的SVV重组衣壳蛋白的透析和浓缩
将如通过蛋白质印迹测定的含有重组蛋白质的蔗糖梯度级分合并在一起，并且分配到10,000MWCO或50,000MWCO纤维素膜透析盒内。将透析盒置于具有磁力搅拌棒的3.5LTBS中，盖上盖子，并且在搅拌板上在4℃下放置最少6小时。然后将透析盒置于3.5L TBS的新鲜烧杯内，并且伴随搅拌进一步透析过夜或更长时间。从透析盒中取出样品，并且根据需要进行浓缩，取决于透析样品的体积。使用尺寸排阻过滤器单元进行浓缩，并且根据制造商的指导离心，直到达到所需的样品体积。
电子显微镜(EM)成像
通过在USDA NADC Facility处的透射电子显微镜检查(EM)，评估蔗糖梯度纯化和透析的重组SVV衣壳蛋白样品，用于VLP的可视化。关于天然SVV的二十面体病毒衣壳的预期大小为直径大约27nm。
结果与讨论
天然SVV P1多蛋白(SEQ ID NO：19，氨基酸1-859)由自切割蛋白酶加工，以形成个别的病毒衣壳亚基蛋白VP1-VP4。以类似于用于FMDV杆状病毒构建体的方式设计本发明中描述的SVV杆状病毒构建体，利用表达的多蛋白自切割成个别的蛋白质亚基，用于形成空衣壳或VLP。用天然编码序列或对于昆虫细胞密码子优化的P1、2A和2B序列(SEQ ID NO：20)，来制备编码全长SVV P1多蛋白、2A、部分2B和3B以及3C(SEQ ID NO：18)的构建体。用类似的基于pVL1393的FMDV杆状病毒构建体的先前研究揭示了归于3C表达的SF+细胞毒性。通过还生成基于pORB的杆状病毒构建体用于评估，解决了关于潜在的SVV 3C毒性的关注。基于pORB的构建体利用内部核糖体进入位点(WSSV sIRES)(SEQ ID NO：32，核酸2647-2826)，允许起始帽不依赖性mRNA翻译，其不同于与多角体蛋白启动子的3'-末端最邻近的序列的5'帽依赖性翻译。几项研究已显示，sIRES(例如来自WSSV的那种)的使用已经常导致放置在sIRES之后的翻译序列的蛋白质表达降低。在所述SVV杆状病毒构建体(SEQ ID NO：32和33)的背景下，sIRES的利用可以减少SVV 3C自切割蛋白酶的表达，其依次又可以缓解3C毒性问题，而不减少SVVP1的表达。基于pORB和基于pVL1393的构建体是相似的，因为它们均利用相同的SVVP1序列，并且包括C末端6x-His标签。然而，基于pORB或pVL1393的构建体之间的主要差异在于，基于pORB的构建体将SVV3C蛋白酶序列置于sIRES位点后面。在构建体的这些初始集合的评估后，又创建了修饰原始SVV DNA序列的两种构建体。一种构建体修饰VP3/VP1切割位点序列(SEQ ID NO：22)，而另一种构建体在SVV3C序列(SEQ ID NO：24)的末端处进一步掺入了SVV3D DNA序列。评估所有构建体的衣壳亚基的表达以及VLP的产生。
SVV衣壳蛋白在杆状病毒感染的昆虫细胞中的表达
BaculoFBU/SVVP13C(SEQ ID NO：18)和BaculoFBU/SVVP13C-CO(SEQ ID NO：20)构建体用于感染SF+细胞，其中收集样品以评估SVV衣壳蛋白的表达。在来自杆状病毒感染的昆虫细胞上清液中，通过用抗SVV P1亚基特异性抗体的蛋白质印迹，检测关于VP1(SEQ IDNO：19，氨基酸596-859)、VP2(SEQ ID NO：19，氨基酸73-356)和VP3(SEQ ID NO：19，氨基酸357-595)衣壳亚基的预期大小的蛋白质条带，其大小与天然SVV衣壳蛋白相似(图4)。有趣的是，在α-SVV VP1和α-SVV VP3蛋白质印迹中检测到～55kDa的另外蛋白质条带。在天然SVV抗原样品或阴性对照中未检测到～55kDa条带(图4)。大小～55kDa的另外蛋白质的存在提示它可能包含未切割的VP3-VP1蛋白质产物。
图4还提供了杆状病毒感染的SF+细胞中的天然(A)(SEQ ID NO：18)和密码子优化的(B)(SEQ ID NO：20)SVV DNA序列之间的SVV衣壳蛋白表达水平的比较。基于这些蛋白质印迹，在密码子优化的BaculoFBU/SVVP13C-CO(SEQ ID NO：20)与原始的天然BaculoFBU/SVVP13C(SEQ ID NO：18)之间，不存在SVV衣壳蛋白表达水平中的明显差异，因此，仅进一步评估了BaculoFBU/SVVP13C(SEQ ID NO：18)构建体。具有置于sIRES后面的3C蛋白酶的第二个构建体集合在SF+昆虫细胞的感染期间未产生可检测的SVV衣壳亚基蛋白。sIRES构建体不仅没有产生可检测水平的SVV衣壳亚单位蛋白，而且未观察到SF+细胞毒性问题。因而，没有进一步评估sIRES构建体。基于这些总体观察，关于BaculoFBU/SVVP13C感染的SF+昆虫细胞的上清液收获物是最有希望的构建体，以前进至蔗糖梯度纯化和VLP存在的评估。
为了测定BaculoFBU/SVVP13C衍生的SVV衣壳蛋白在蔗糖梯度中的预期迁移率，将形成团块的天然SVV病毒在蔗糖梯度上分开，并且通过蛋白质印迹进行分析(图5A)。在关于天然SVV的蔗糖梯度纯化后，在级分5和6中检测到大多数天然SVV亚基蛋白。预计如果VLP在杆状病毒感染的SF+细胞中形成，则它们将存在于相似或略微更高的收集梯度级分范围内。
来自BaculoFBU/SVVP13C构建体的收获物上清液也进行加工用于蔗糖梯度纯化。蔗糖梯度级分的蛋白质印迹仅在蔗糖级分一中的一小部分重组SVV VP2衣壳蛋白中检测到(图5B)。在蔗糖级分中未检测到VP1和VP3，尽管通过α-SVV VP1蛋白质印迹，在蔗糖级分各处检测到在～55kDa处的微弱蛋白质条带，被认为是未切割的VP3-VP1。与从天然SVV中检测到的预期蛋白质形成对比，在级分5和6中未检测到重组SVV衣壳蛋白。这些结果提示，在BaculoFBU/SVVP13C感染的昆虫细胞中表达的衣壳亚基蛋白不形成VLP。
即使BaculoFBU/SVVP13C(SEQ ID NO：18)产生用α-SVV抗体作为亚基蛋白检测到的重组SVV衣壳蛋白，但未观察到VLP。当与天然SVV病毒蛋白相比较时，衣壳亚基蛋白具有相似的大小，但在杆状病毒感染的SF+细胞中也检测到几个其它蛋白质条带，包括在α-SVVVP1和α-SVV VP3蛋白质印迹中的～55kDa处的蛋白质条带，提示天然SVV病毒中不存在未切割的VP3-VP1蛋白产物。这可能指示关于VP3-VP1亚基的有效切割和分开的问题，其依次又可能阻碍杆状病毒感染的昆虫细胞中的VLP形成。
修饰的BaculoFBU/SVVP13C构建体的评估
为了调查SVV衣壳亚基蛋白VP1和VP3不能完全分开的可能性，基于先前的出版物设计了两种新的构建体。通过Hales等人的2008年出版物陈述了SVV P1 VP3/VP1切割位点FH/ST是非典型的微小核糖核酸病毒，包括与SVV最密切相关的属，心病毒属。相比之下，PQ/GV的典型切割位点在许多已知的微小核糖核酸病毒中是保守的。因此，VP3/VP1切割位点突变为典型的微小核糖核酸病毒切割序列可以增强VP3和VP1衣壳亚基的切割。使BaculoFBU/SVVP13C(SEQ ID NO：18)构建体突变，以在VP3/VP1界面处含有PQ/GV序列，导致指定为BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO：22)的构建体。这种新的构建体用于感染SF+细胞，并且以与BaculoFBU/SVVP13C构建体(SEQ ID NO：18)相似的方式在蛋白质表达评价中进行评估。使用α-SVVVP1或α-SVVVP3抗体的BaculoFBU/SVVP13C VP3/VP1衍生的上清液样品的蛋白质印迹分析，检测到推定的未切割的VP3-VP1蛋白产物、以及以与从BaculoFBU/SVVP13C(SEQ ID NO：18)观察到的相同比例的VP3或VP1条带的个别亚基(图6)。在BaculoFBU/SVVP13C VP3/VP1收获物上清液中也检测到在SVV P1多蛋白的预期全长处的蛋白质条带，～95kDa。
另外，收获物上清液的蔗糖梯度级分的蛋白质印迹评估(图7)与BaculoFBU/SVVP13C(SEQ ID NO：18)的结果可比较。α-SVV VP2蛋白质印迹检测到在蔗糖级分各处的重组SVV VP2衣壳蛋白，其中大部分在级分一和九中。在蔗糖级分中未检测到亚基VP1和VP3蛋白，尽管在α-VP1蛋白的蔗糖级分各处、以及在α-VP3蛋白质的蔗糖级分一和九中检测到在～55kDa处的蛋白质条带，其可能是VP3-VP1未切割的蛋白质。所有三个蛋白质都具有在最后一个蔗糖级分中检测到的几个蛋白质条带，其看起来与蔗糖梯度的起始样品相似。这提示SVV衣壳蛋白可能聚集并沉淀到梯度的底部。衣壳蛋白在图5b中的BaculoFBU/SVVP13C(SEQ ID NO：18)蔗糖梯度蛋白质的最后一个级分中未检测到，但在先前的评估中观察到(NB 3219-123)。根据这些蛋白质评估看起来，切割序列从FH/ST到PQ/GV的突变对被视为未切割的VP3-VP1的～55kDa条带的存在没有作用。与原始构建体相比，未检测到亚基VP3和VP1蛋白的量中的增加，并且也未观察到VLP形成。
当天然病毒中具有3CD蛋白酶时，在微小核糖核酸病毒内的其它属包括肠道病毒和口疮病毒已显示更有效的VP3-VP1切割；因此，设计了第二种塞内卡病毒构建体BaculoFBU/SVVP13CD(SEQ ID NO：24)。BaculoFBU/SVVP13CD(SEQ ID NO：24)在SF+细胞中表达，并且通过蛋白质印迹评估上清液收获物(图8)。观察到与先前的VLP评价可比较的结果，其中在α-SVV VP1和α-SVV VP3蛋白质印迹中检测到VP1、VP2和VP3亚基，以及～55kDa的可疑的未切割的VP3-VP1蛋白。
与用其它SVV杆状病毒构建体的SVV蛋白质表达评价形成对比，关于BaculoFBU/SVVP13CD(SEQ ID NO：24)的蔗糖级分的蛋白质印迹评估显示出存在于蔗糖级分1和2中的单体SVV VP1、VP2和VP3衣壳亚基蛋白，其中在蔗糖级分各处检测到VP1和VP2。～55kDa蛋白质条带存在于蔗糖级分1和2中的α-SVV VP1和α-SVV VP3蛋白质印迹中，但不存在于阴性对照样品或α-SVV VP2蛋白质印迹中(图9)。类似于BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO：22)蔗糖级分评估，大部分SVV衣壳蛋白聚集并沉淀到关于BaculoFBU/SVVP13CD(SEQ IDNO：24)的蔗糖梯度底部。然而，在衍生自BaculoFBU/SVVP13CD感染的SF+细胞构建体的级分各处检测到SVV VP1和VP2亚基蛋白提示了VLP形成的可能性。
尽管来自每种构建体的蔗糖梯度评估的不明确结果，仍通过在USDA NADC处的电子显微镜检查(EM)评估预期含有VLP的级分。来自上清液收获物BaculoFBU/SVVP13C(SEQID NO:18)、BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO:22)和BaculoFBU/SVVP13CD(SEQ IDNO:24)的合并的蔗糖级分在TBS中进行透析，并且在制剂中进行浓缩用于EM成像。样品具有较高的背景，使得难以通过EM阴性染色明确地描绘VLP。在BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO:22)和BaculoFBU/SVVP13CD(SEQ ID NO:24)合并的蔗糖级分中稀疏地可见一些球形，其大小与预期的SVV VLP相似，但在样品各处不存在足够的球形以确认VLP的存在。
重组SVV蛋白在SF+昆虫细胞内部表达
关于为何在上清液中检测到个别重组SVV病毒衣壳蛋白，但看起来没有形成VLP的一种可能性是，由于昆虫细胞培养基的低pH，VLP在释放到上清液内之后不久可能解离。为了测试这一假设，来自BaculoFBU/SVVP13C(SEQ ID NO:18)、BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO:22)和BaculoFBU/SVVP13CD(SEQ ID NO:24)感染的第3天(当细胞的活力仍相对较高时)的细胞团块样品，在生理pH缓冲液中裂解，以获得可溶性蛋白质级分，用于通过蛋白质印迹评估重组SVV亚基蛋白(图10)。如用杆状SVV构建体的上清液收获物样品可见的，在第3天的可溶性级分中存在可检测水平的亚基衣壳蛋白VP1、VP2和VP3。如先前观察到的，在杆状SVV样品泳道中的α-SVV VP1和α-SVV VP3蛋白质中，也检测到疑为未切割的VP3-VP1蛋白的～55kDa条带。第3天可溶性级分样品进行蔗糖梯度纯化，并且通过蛋白质印迹进行评估，以观察VLP是否存在于裂解前的细胞中(图11)。
如分别用来自由BaculoFBU/SVVP13C(SEQ ID NO:18)、BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO:22)和BaculoFBU/SVVP13CD(SEQ ID NO:24)感染的昆虫细胞的上清液收获物蔗糖级分可见的，来自第3天可溶性级分的蔗糖级分具有可比较的结果。预期为SVV衣壳蛋白的蛋白条带大部分在级分一和二中检测到和/或沉淀到底部，提示昆虫细胞内部的SVV亚基蛋白在细胞裂解前不形成VLP。对BaculoFBU/SVVP13C VP3/VP1(SEQ ID NO：22)第3天可溶性样品的合并的蔗糖级分进行EM，其中对于这种样品未观察到VLP。BaculoFBU/SVVP13C(SEQ ID NO：18)和BaculoFBU/SVVP13CD(SEQ ID NO：24)第3天可溶性蔗糖级分未通过EM进行评估。
结论
尽管测定重组SVV病毒衣壳蛋白VP1、VP2和VP3在某种程度上被表达为完全切割的蛋白质，但基于蔗糖梯度纯化和EM成像，它们并未导致VLP形成。在蔗糖梯度级分的蛋白质印迹评估中，在梯度的前几个级分和/或最后一个级分中检测到重组SVV衣壳蛋白。这些结果提示，蛋白质并不组装成VLP，而是作为非结合单体保留或形成大聚集体，指示错误折叠或错误组装的蛋白质。电子显微镜检查支持这些结果，因为在含有SVV衣壳亚基蛋白的合并的蔗糖级分中未检测到VLP。
实施例3
这项研究利用常规动物来测定疫苗施用后的血清学应答诱导的初步可行性。这项研究的主要目的是评估原型疫苗BaculoFBU/SVVP13C(SEQ ID NO:18)、BaculoFBU/SVVP13CVP3/VP1(SEQ ID NO:22)和BaculoFBU/SVVP13CD(SEQ ID NO:24)的施用是否导致在常规猪中的血清转化。
如表1中所示，将四十头猪随机分成四组。关于组的描述和住房结构，参见下表6。在D0时，向猪施用2mL肌内剂量的原型疫苗或安慰剂。在第21时，动物接受原型疫苗或安慰剂的加强施用。在每次疫苗接种(D0和D21)和D35时的治疗施用之前，从所有猪中收集血液。就血清转化为SVA的证据测定血清样品的子集。在研究自始至终记录一般健康观察。在疫苗施用后观察注射部位的反应最少三天。在试验结束时对动物实施人道安乐死。关于关键事件和样品收集的时间表，参见表7。
表6：研究设计
Figure BDA0002360499750000351
表7.关键事件和样品收集的时间表
Figure BDA0002360499750000352
Figure BDA0002360499750000361
*注意观察持续直到反应消退
为了避免偏差，通过不涉及动物临床监测的人员在D0和D21时施用治疗。在D0时，使用适当大小的无菌针头和注射器，将2mL剂量的疫苗施用于健康猪的右颈部的肌肉组织内。在D21时，该过程相同，除了注射在颈部的左侧给予之外。在疫苗剂量确认记录(VaccineDose Confirmation Record)上，记录批号、剂量的量、动物标识号和疫苗材料的施用时机。
在疫苗接种期过程中，每天使用一般健康观察表对动物进行评估。具体地，如果所有动物都是正常的，则对于状态输入N。如果发现异常猪，则对于状态输入A，并且列出具体动物标识号和异常。每次疫苗接种后，监测注射部位区域的发红、肿胀、发热和疼痛的存在(或存在或不存在)和大小(cm)至少三天。如果病变显而易见，则监测它们直至消退。
在血液收集日，使用适当大小的
Figure BDA0002360499750000362
针、
Figure BDA0002360499750000363
持针器(两者均从Becton Dickinson and Company Corporation商购可得)和适当大小的血清分离管(SST)，通过研究人员或指定人员经由前腔静脉从每头猪中收集三至八mL静脉全血。
将血清样品保持在2-8℃下直至测试。加工在收到后48小时内完成。血液管在4℃下以1960x g离心10分钟。血清通过离心与凝块分开，并且倾析到两个螺旋盖低温小瓶内，所述小瓶标有至少研究编号、研究日和动物ID。等分试样贮存于-70℃±10℃下。在这项研究完成后，样品贮存最少六个月。
实施例4
这项研究利用常规动物来评估两剂量的塞内卡病毒A疫苗、灭活的全病毒针对异源塞内卡病毒A野外分离株的异源攻击的功效。总共25头猪用于该研究。将动物随机分成两个治疗组。在第D0天时，SVA-Vx组中的十三头猪用塞内卡病毒A疫苗(灭活的全病毒)进行肌内(IM)接种，而安慰剂组中的剩余十二头猪接受对照产品。在第14天时，使用适当的材料，对所有猪肌内施用加强疫苗。在D35时，所有猪都用总体积为5mL(经口2mL和鼻内3mL)的8.36log TCID50/剂量的异源塞内卡病毒A野外分离株(病毒收获物)进行攻击。所有的猪都混合饲养在一个房间里。从D0到D33每天监测猪的一般健康。从D34到D49，每天监测猪的与SVA感染相关的临床体征。在研究自始至终定期获取血液和直肠温度。在D49(攻击后14天)时，对所有动物进行尸检。关于实验设计概括，参见表8。
表8.研究设计
Figure BDA0002360499750000371
关于疫苗和对照产品制剂的概括，参见下表9。对疫苗材料进行常规培养和支原体属物种(Mycoplasma sp.)PCR；未检测到生长(血琼脂上的厌氧或好氧)或支原体DNA污染。使用适当大小的无菌针和注射器，在D0时，将疫苗肌内施用到颈部的右侧内，在耳根与肩点之间的中间位置。在第14天时，疫苗在与先前所述相同的位置中施用，但在颈部的左侧上。所有组都接受2mL剂量。
表9.疫苗和对照
Figure BDA0002360499750000372
基于来自野外病例和先前出版物的报道，监测动物的跛行、蹄病变和水泡的存在。如果动物在研究自始至终具有任何临床异常，则它被视为受影响的。表10按组报告了受影响动物的频率。预防分数估计值0.322(0.004，0.539；95％CI)指示疫苗接种减少受影响动物的数目。还对动物表展示异常临床体征的天数完成缓解分数分析。缓解分数估计值0.710(0.333，0.935；95％CI)指示疫苗接种减少动物视为受影响的天数。
表10.在攻击期过程中按组的临床体征存在/不存在的频率分布
Figure BDA0002360499750000373
*受影响＝临床体征在研究期间观察到至少一次
Figure BDA0002360499750000374
动物#648从分析中去除
在攻击期过程中收集直肠温度；图12中呈现了按研究日和组的最小均方直肠温度。疫苗接种导致在D40和42时显著降低的温度。
通过病毒中和测定评估来自D0、14、35和49的血清样品。表11中呈现了按组和研究日的几何平均滴度。在两个剂量的疫苗后，13/13(100％)个动物具有大于400的中和滴度。
表11.关于按研究日和组的病毒中和滴度的概括统计。<40的值报告为20；>2560的值设为2560。
Figure BDA0002360499750000381
通过qRT-PCR测定检测血清中病毒RNA的存在。图13展示了血清中SVA RNA的组中值数量(log10基因组拷贝/mL)。在研究期间的任何时间，在接种疫苗的动物中未检测到SVARNA。相比之下，从D36直到D42，在安慰剂组中检测到病毒血症。
总之，用两个剂量的塞内卡病毒A(灭活的全病毒)的疫苗接种导致病毒血症的完全减少、临床体征中的统计学显著减少(PF＝0.322；95％CI＝0.004，0.539)、以及在13/13个疫苗接种的动物中攻击前4倍的病毒中和滴度。
根据本公开内容，无需过度实验即可制备且实施本文公开且请求保护的所有组合物和方法。尽管本发明的组合物和方法已根据优选实施方案进行描述，但对于本领域技术人员而言显而易见的是，可以对组合物和方法以及在本文中描述的方法的步骤或步骤顺序应用变化，而不背离本发明的概念、精神和范围。更具体地，显而易见的是，化学和生理学相关的某些试剂可以取代本文所述的试剂，同时达到相同或相似的结果。对于本领域技术人员显而易见的所有此类相似的取代和修改都视为在如由下述权利要求限定的本发明的精神，范围和概念内。
序列表
<110> 勃林格殷格翰动物保健美国有限公司
<120> 塞内卡病毒A免疫原性组合物及其方法
<130> 10-0177-WO-1
<160> 45
<170> PatentIn version 3.5
<210> 1
<211> 7221
<212> RNA
<213> 塞内卡病毒
<400> 1
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<210> 2
<211> 6546
<212> RNA
<213> 塞内卡病毒
<400> 2
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aacgucccuu aucaaccucc uuuguucuac acauacaugu cagaguacgc ucaucggguu 5400
uucuccuuuu ugggaaaaga caaugacauu cugaccguca aagaagcaau ccugggcauc 5460
ccuggacuag acccuaugga uccccacaca gcuccggguu ugcccuacgc cauuagcggc 5520
cuucgacgua cugaucucgu cgauuuugcg aacggcacgg uagacccggc acuggccaug 5580
cagauccaga aauucuuaga cggugacuac ucugaucaug ucuuccaaac uuuucugaaa 5640
gaugaaauca gacccucaga gaagguccgg gcgggaaaaa cccgcauugu cgaugugccc 5700
ucccuggcgc acugcauugu gggcagaaug cugcuugggc gcuuugccgc caaguuucaa 5760
ucccauccug gcuuucuccu uggcuccgcu aucgggucug acccugaugu cuucuggacc 5820
gucauagggg cucagcucga gggaagaaag aacacguaug acguggacua cagugccuuu 5880
gacucuucac acggcacugg cuccuucgag gcucucaucu cucacuuuuu caccguggac 5940
aaugguuuca gcccugcgcu gggaccguau cucagauccc uggcugucuc ggugcacgcu 6000
uacggcgagc gucgcaucaa gauuaccgga ggccuccccu cugguugugc cgcgaccagc 6060
cugcugaaca cagugcucaa caaugugauc aucaggacug cucuggcauu gaccuacaag 6120
gaauuugaau augacauggu ugauaucauc gccuacggug acgaccuucu gguugguacg 6180
gauuaugauc uggacuucaa ugagguggcg cggcgcgcug ccaaacuggg guauaagaug 6240
acuccugcca acaaggguuc ugucuucccu ccgacuuccu cucucuccga ugcuguuuuu 6300
cuaaaacgca aauucgucca aaacaaugac ggcuuauaua aaccaguuau ggauuuaaag 6360
aauuuggaag ccaugcucuc cuacuucaaa ccaggaacac uacucgagaa gcugcaaucu 6420
guuucuaugu uggcucaaca uucuggaaaa gaagaauacg auagauugau gcaccccuuc 6480
gcugacuaug gugccguacc gagucacgag uaccugcagg caagauggag ggccuuguuc 6540
gacuga 6546
<210> 3
<211> 2181
<212> PRT
<213> 塞内卡病毒
<400> 3
Met Gln Asn Ser His Phe Ser Phe Asp Thr Ala Ser Gly Thr Phe Glu
1 5 10 15
Asp Val Thr Gly Thr Lys Val Lys Ile Val Glu His Pro Arg Ser Val
20 25 30
Asn Asn Gly Val Tyr Asp Ser Ser Thr His Leu Glu Ile Leu Asn Leu
35 40 45
Gln Gly Glu Ile Glu Ile Leu Lys Ser Phe Asn Glu Tyr Gln Ile Arg
50 55 60
Ala Ala Lys Gln Gln Leu Gly Leu Asp Ile Val Tyr Glu Leu Gln Gly
65 70 75 80
Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly Asn Asn
85 90 95
Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn Ser Val
100 105 110
Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly Asn Ser
115 120 125
Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile Leu Asn
130 135 140
Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu Asn Ser
145 150 155 160
Ala Asp Arg Val Ile Thr Gln Thr Ala Gly Asn Thr Ala Ile Asn Thr
165 170 175
Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro Thr Lys
180 185 190
Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr Phe Thr
195 200 205
Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr Lys Ala
210 215 220
Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala Phe Leu
225 230 235 240
Ser Arg Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr Leu His
245 250 255
Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln Cys Asn
260 265 270
Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val Pro Glu
275 280 285
Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu Gln Glu
290 295 300
Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg Thr Gly
305 310 315 320
Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro Pro Asn
325 330 335
Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr Val Phe
340 345 350
Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp Ile Ser
355 360 365
Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr Gln Asn
370 375 380
Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr Lys Glu
385 390 395 400
Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro Thr Ser
405 410 415
Pro Tyr Phe Asn Gly Leu Arg Asn Arg Phe Lys Thr Gly Thr Asp Glu
420 425 430
Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu Met Phe
435 440 445
Leu Ser Thr Ile Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn Val Arg
450 455 460
Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu Leu Gln
465 470 475 480
Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Gly Arg Ala Ser Glu Pro
485 490 495
Glu Pro Ala Ser Asp Ala Tyr Val Pro Tyr Val Ala Val Pro Ala Gln
500 505 510
Phe Asp Asp Lys Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser Asp Pro
515 520 525
Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe Ala Asn
530 535 540
Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro Met Met
545 550 555 560
Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly Ala Gln
565 570 575
Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile Trp Asp
580 585 590
Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Ile Pro Tyr Ile Ser Pro
595 600 605
Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr Ser Ala
610 615 620
Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu Pro Pro
625 630 635 640
Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala Gly Glu
645 650 655
Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr Val Phe
660 665 670
His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly Asn Thr
675 680 685
Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn His Thr
690 695 700
Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val Ile Lys
705 710 715 720
Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr Ala Thr
725 730 735
Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro Arg Pro
740 745 750
Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Val Asn Pro
755 760 765
Ser Asp Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn Phe Tyr
770 775 780
Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val Thr Val
785 790 795 800
Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe Pro Ser
805 810 815
Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu His Val
820 825 830
Pro Tyr His Phe Thr Gly Arg Thr Pro Arg Ala Phe Thr Ser Lys Gly
835 840 845
Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser Val Leu
850 855 860
Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr Arg Gly
865 870 875 880
Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Ile Pro Arg
885 890 895
Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val Tyr Val
900 905 910
Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro Phe Arg
915 920 925
Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Val Glu Thr Asn
930 935 940
Pro Gly Pro Ala Ser Asp Asn Pro Ile Leu Glu Phe Leu Glu Ala Glu
945 950 955 960
Asn Asp Leu Val Thr Leu Ala Ser Leu Trp Lys Met Val His Ser Val
965 970 975
Gln Gln Thr Trp Arg Lys Tyr Val Lys Asn Asp Asn Phe Trp Pro Asn
980 985 990
Leu Leu Ser Glu Leu Val Gly Glu Gly Ser Ile Ala Leu Ala Ala Thr
995 1000 1005
Leu Ser Asn Gln Ala Ser Val Lys Ala Leu Leu Gly Leu His Phe
1010 1015 1020
Leu Ser Arg Gly Leu Asn Tyr Thr Asp Phe Tyr Ser Leu Leu Ile
1025 1030 1035
Glu Lys Cys Ser Ser Phe Phe Thr Val Glu Pro Pro Pro Pro Pro
1040 1045 1050
Ala Glu Asn Leu Met Thr Lys Pro Ser Val Lys Ser Lys Phe Arg
1055 1060 1065
Lys Leu Phe Lys Met Gln Gly Pro Met Asp Thr Val Lys Asp Trp
1070 1075 1080
Asn Gln Ile Ala Ala Gly Leu Lys Asn Phe Gln Phe Val Arg Asp
1085 1090 1095
Leu Val Lys Glu Val Val Asp Trp Leu Gln Ala Trp Ile Asn Lys
1100 1105 1110
Glu Lys Ala Ser Pro Val Leu Gln Tyr Gln Leu Glu Met Lys Lys
1115 1120 1125
Leu Gly Pro Val Ala Leu Ala His Asp Ala Phe Met Ala Gly Ser
1130 1135 1140
Gly Pro Pro Leu Gly Asp Asp Gln Ile Glu Tyr Leu Gln Asn Leu
1145 1150 1155
Lys Ser Leu Ala Leu Thr Leu Gly Lys Thr Asn Leu Ala Gln Ser
1160 1165 1170
Leu Thr Thr Met Ile Asn Ala Lys Gln Ser Ser Ala Gln Arg Val
1175 1180 1185
Glu Pro Val Val Val Val Leu Arg Gly Lys Pro Gly Cys Gly Lys
1190 1195 1200
Ser Leu Ala Ser Thr Leu Ile Ala Gln Ala Val Ser Lys Arg Leu
1205 1210 1215
Tyr Gly Ser Gln Ser Val Tyr Ser Leu Pro Pro Asp Pro Asp Phe
1220 1225 1230
Phe Asp Gly Tyr Lys Gly Gln Phe Val Thr Leu Met Asp Asp Leu
1235 1240 1245
Gly Gln Asn Pro Asp Gly Gln Asp Phe Ser Thr Phe Cys Gln Met
1250 1255 1260
Val Ser Thr Ala Gln Phe Leu Pro Asn Met Ala Asp Leu Ala Glu
1265 1270 1275
Lys Gly Arg Pro Phe Thr Ser Asn Leu Ile Ile Ala Thr Thr Asn
1280 1285 1290
Leu Pro His Phe Ser Pro Val Thr Ile Ala Asp Pro Ser Ala Val
1295 1300 1305
Ser Arg Arg Ile Asn Tyr Asp Leu Thr Leu Glu Val Ser Glu Ala
1310 1315 1320
Tyr Lys Lys His Thr Arg Leu Asn Phe Asp Leu Ala Phe Arg Arg
1325 1330 1335
Thr Asp Ala Pro Pro Ile Tyr Pro Phe Ala Ala His Val Pro Phe
1340 1345 1350
Val Asp Val Ala Val Arg Phe Lys Asn Gly His Gln Ser Phe Asn
1355 1360 1365
Leu Leu Glu Leu Val Asp Ser Ile Cys Ala Asp Ile Arg Ala Lys
1370 1375 1380
Gln Gln Gly Ala Arg Asn Met Gln Thr Leu Val Leu Gln Ser Pro
1385 1390 1395
Asn Glu Asn Asp Asp Thr Pro Val Asp Glu Ala Leu Gly Arg Val
1400 1405 1410
Leu Thr Pro Ala Ala Val Asp Glu Ala Leu Val Asp Leu Ala Pro
1415 1420 1425
Asp Ala Asp Pro Val Gly Arg Leu Ala Ile Leu Ala Lys Leu Gly
1430 1435 1440
Leu Ala Leu Ala Ala Val Thr Pro Gly Leu Ile Ile Leu Ala Val
1445 1450 1455
Gly Leu Tyr Lys Tyr Phe Ser Gly Ser Asp Thr Asp Gln Glu Glu
1460 1465 1470
Thr Glu Ser Glu Glu Pro Ala Lys Val Pro Arg Ser Glu Asn Ala
1475 1480 1485
Tyr Asp Gly Pro Lys Lys Asn Ser Lys Pro Pro Gly Ala Leu Ser
1490 1495 1500
Leu Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala
1505 1510 1515
Ala Val Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro
1520 1525 1530
Asn Arg Pro Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Ala Gly
1535 1540 1545
Arg Thr Phe Leu Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp
1550 1555 1560
Thr Ser Phe Thr Ile Arg Gly Glu Val His Thr Arg Asp Glu Pro
1565 1570 1575
Phe Gln Thr Val His Phe Thr His His Gly Leu Pro Thr Asp Leu
1580 1585 1590
Met Met Val Arg Leu Gly Pro Gly Asn Ser Phe Pro Asn Asn Leu
1595 1600 1605
Asp Lys Phe Gly Leu Asp Gln Met Pro Ala Arg Asn Ser Arg Val
1610 1615 1620
Val Gly Val Ser Ala Ser Tyr Gly Asn Phe Phe Phe Ser Gly Asn
1625 1630 1635
Phe Leu Gly Phe Val Asp Ser Ile Thr Ser Asp Gln Gly Thr Tyr
1640 1645 1650
Ala Arg Leu Phe Arg Tyr Arg Val Thr Thr Tyr Lys Gly Trp Cys
1655 1660 1665
Gly Ser Ala Leu Val Cys Glu Ala Gly Gly Val Arg Arg Ile Ile
1670 1675 1680
Gly Met His Ser Ala Gly Ala Ala Gly Ile Gly Ala Gly Thr Tyr
1685 1690 1695
Ile Ser Lys Leu Gly Leu Ile Lys Ala Leu Lys His Leu Gly Glu
1700 1705 1710
Pro Leu Ala Thr Met Gln Gly Leu Met Thr Glu Leu Glu Pro Gly
1715 1720 1725
Val Thr Val His Val Pro Arg Lys Ser Lys Leu Arg Lys Thr Thr
1730 1735 1740
Ala His Ala Val Tyr Lys Pro Glu Phe Glu Pro Ala Val Leu Ser
1745 1750 1755
Lys Phe Asp Pro Arg Leu Asn Lys Asp Val Asp Leu Asp Glu Val
1760 1765 1770
Ile Trp Ser Lys His Thr Ala Asn Val Pro Tyr Gln Pro Pro Leu
1775 1780 1785
Phe Tyr Thr Tyr Met Ser Glu Tyr Ala His Arg Val Phe Ser Phe
1790 1795 1800
Leu Gly Lys Asp Asn Asp Ile Leu Thr Val Lys Glu Ala Ile Leu
1805 1810 1815
Gly Ile Pro Gly Leu Asp Pro Met Asp Pro His Thr Ala Pro Gly
1820 1825 1830
Leu Pro Tyr Ala Ile Ser Gly Leu Arg Arg Thr Asp Leu Val Asp
1835 1840 1845
Phe Ala Asn Gly Thr Val Asp Pro Ala Leu Ala Met Gln Ile Gln
1850 1855 1860
Lys Phe Leu Asp Gly Asp Tyr Ser Asp His Val Phe Gln Thr Phe
1865 1870 1875
Leu Lys Asp Glu Ile Arg Pro Ser Glu Lys Val Arg Ala Gly Lys
1880 1885 1890
Thr Arg Ile Val Asp Val Pro Ser Leu Ala His Cys Ile Val Gly
1895 1900 1905
Arg Met Leu Leu Gly Arg Phe Ala Ala Lys Phe Gln Ser His Pro
1910 1915 1920
Gly Phe Leu Leu Gly Ser Ala Ile Gly Ser Asp Pro Asp Val Phe
1925 1930 1935
Trp Thr Val Ile Gly Ala Gln Leu Glu Gly Arg Lys Asn Thr Tyr
1940 1945 1950
Asp Val Asp Tyr Ser Ala Phe Asp Ser Ser His Gly Thr Gly Ser
1955 1960 1965
Phe Glu Ala Leu Ile Ser His Phe Phe Thr Val Asp Asn Gly Phe
1970 1975 1980
Ser Pro Ala Leu Gly Pro Tyr Leu Arg Ser Leu Ala Val Ser Val
1985 1990 1995
His Ala Tyr Gly Glu Arg Arg Ile Lys Ile Thr Gly Gly Leu Pro
2000 2005 2010
Ser Gly Cys Ala Ala Thr Ser Leu Leu Asn Thr Val Leu Asn Asn
2015 2020 2025
Val Ile Ile Arg Thr Ala Leu Ala Leu Thr Tyr Lys Glu Phe Glu
2030 2035 2040
Tyr Asp Met Val Asp Ile Ile Ala Tyr Gly Asp Asp Leu Leu Val
2045 2050 2055
Gly Thr Asp Tyr Asp Leu Asp Phe Asn Glu Val Ala Arg Arg Ala
2060 2065 2070
Ala Lys Leu Gly Tyr Lys Met Thr Pro Ala Asn Lys Gly Ser Val
2075 2080 2085
Phe Pro Pro Thr Ser Ser Leu Ser Asp Ala Val Phe Leu Lys Arg
2090 2095 2100
Lys Phe Val Gln Asn Asn Asp Gly Leu Tyr Lys Pro Val Met Asp
2105 2110 2115
Leu Lys Asn Leu Glu Ala Met Leu Ser Tyr Phe Lys Pro Gly Thr
2120 2125 2130
Leu Leu Glu Lys Leu Gln Ser Val Ser Met Leu Ala Gln His Ser
2135 2140 2145
Gly Lys Glu Glu Tyr Asp Arg Leu Met His Pro Phe Ala Asp Tyr
2150 2155 2160
Gly Ala Val Pro Ser His Glu Tyr Leu Gln Ala Arg Trp Arg Ala
2165 2170 2175
Leu Phe Asp
2180
<210> 4
<211> 7300
<212> RNA
<213> 塞内卡病毒
<400> 4
uuugaaaugg ggggcugggc ccucaugccc aguccuuccu uuccccuucc gggggguaaa 60
ccggcugugu uugcuagagg cacagaggag caacauccaa ccugcucuug uggggaacgg 120
ugcggcucca auuccugcgu cgccaaaggu guuagcgcac ccaaacggcg caucuaccaa 180
ugcuauuggu guggucugcg aguucuagcc uacucguuuc uccccuaucc acucacucac 240
gcacaaaaag uguguuguaa cuacaagacu uagcccucgc acgagaugug cgauaaccgc 300
aagauugacu caagcgcgga aagcgcugua accacaugcu guuagucccu uuauggcugc 360
gagauggcua uccaccucgg aucacugaac uggagcucga cccuccuuag uaagggaacc 420
gagaggccuu cuugcaacaa gcuccgacac agaguccacg ugauugcuac caccaugagu 480
acaugguucu ccccucucga cccaggacuu cuuuuugaau auccacggcu cgauccagag 540
gguggggcau gaucccccua gcauagcgag cuacagcggg aacuguagcu aggccuuagc 600
gugcuuugga uacugccuga uagggcgacg gccuagucgu gucgguucua uagguagcac 660
auacaaauau gcagaacucu cauuuuucuu ucgauacagc cucuggcacc uuugaagacg 720
uaaccggaac aaaagucaag aucguugaau acccuagauc ggugaacaau gguguuuacg 780
auucguccac ucauuuagag auacugaacc uacaggguga aauugaaauu uuaaggucuu 840
ucaaugaaua ccaaauucgc gccgccaaac aacaacuugg acuggacauc guauaugaac 900
uacaggguaa uguucagaca accucaaaga augauuuuga uucccgcggc aauaauggua 960
acaugaccuu caauuacuac gcaaacacuu aucagaauuc aguagacuuc ucgaccuccu 1020
cgucggcguc aggcgccgga cccgggaacu cccggggcgg auuagcgggu cuccucacaa 1080
auuucagugg aaucuugaac ccucuuggcu accucaaaga ccacaauacc gaagaaaugg 1140
aaaacucugc ugaucgaguc auaacacaaa cggcgggcaa cacugccaua aacacgcaau 1200
caucacuggg uguguugugu gccuacguug aagacccgac caaaucugac ccuccgucca 1260
gcagcacaga ucaacccacc accacuuuua cugccaucga caggugguac acuggacgcc 1320
ucaauucuug gacaaaagcu guaaaaaccu ucucuuuuca ggccgucccg cucccuggag 1380
ccuuccuguc uagacaggga ggccucaaug gaggggccuu cacggcuacc cuacauagac 1440
auuucuuaau gaagugcggg uggcaggugc agguccaaug caauuugaca caauuccacc 1500
aaggugcucu ucuuguugcc augguccccg aaaccacccu ugaugucaag cccgacggca 1560
aggcaaagag ccuacaggag cugaaugaag agcagugggu agaaaugucu gacgauuacc 1620
ggaccgggaa aaacaugccu uuucagucuc uuggcacaua cuaucggccc ccuaacugga 1680
cuuggggccc uaauuucauc aaccccuauc aaguaacagu uuucccacac caaauucuga 1740
acgcgagaac cucuaccucg guagacauaa gugucccaua caucggggag acuccuacac 1800
aauccucaga gacacagaac uccuggaccc uccucguuau ggugcuuguc ccccuggacu 1860
acaaggaggg agccacaacu gacccagaaa uuacauuuuc cguaaggccu acaaguccuu 1920
acuucaaugg gcuucguaac cgcuacaaga ccgggacgga cgaggaacag gggcccauuc 1980
ccacagcacc cagagaaaau ucgcuuaugu uucucucgac caucccugac gacacugucc 2040
cugcuuacgg gaaugugcgu accccucccg ucaauuaccu uccuggugaa auaaccgacc 2100
ucuuacaacu ggcccguaua cccacucuca uggcguuugg gcgggugccu gaaccugaac 2160
cugccucaga cgcuuaugug cccuacguug ccguucccac ccaguucgau gacaagccuc 2220
ucaucuccuu cccgaucacc cuuucagauc cugucuacca gaauacucug guaggcgcca 2280
ucaguucaaa uuucgccaac uaccgggggu guauccaaau cacucugaca uuuuguggac 2340
cuaugauggc aagagggaaa uuccuacucu cguauucucc cccaaaugga acacaaccac 2400
agacccuuuc ugaagccaug cagugcacau auucuauuug ggauauaggc uuaaacucua 2460
guuggaccuu ugucaucccc uacaucucgc ccagugacua ccgugaaacu cgggccauua 2520
ccaauucggu uuauucugcu gauggcuggu uuagccugca caagcugacc aaaauuacuc 2580
uaccaccuga uugcccacag agccccugua uucucuuuuu cgccucugcu ggugaggauu 2640
acacccuccg ucuccccguu gauuguaauc cuucuuaugu guuccacucc accgacaacg 2700
ccgagacugg gguuauugag gcggguaaca cugacaccga uuucucuggu gaauuggcgg 2760
cuccuggcuc uaaccacacu aaugucaagu uccuguuuga ccgaucucga uuacugaaug 2820
uaauuaaggu acuggagaag gacgccgucu ucccccgccc uuuccccaca gcaacuggua 2880
cacaacagga cgaugguuac uuuugucuuc uaacaccccg cccaacaguc gccucccgac 2940
ccgccacucg uuucggccug uacgucaguc cgucugacag uggcguucuc gccaacacuu 3000
cacuggauuu caauuuuuac agcuuggccu guuucacuua cuuuagauca gaccuugaag 3060
ucacgguggu cucacuggag ccagaucugg aauucgcugu agggugguuc cccucuggca 3120
gugaguacca ggcuuccagc uuugucuacg accaacugca uguacccuac cacuuuacug 3180
ggcgcacucc ccgcgcuuuc gccagcaagg gugggaaggu aucuuucgug cucccuugga 3240
acucugucuc auccgugcuu cccgugcgcu gggggggcgc uuccaagcuu ucuucugcca 3300
cgcggggucu gccggcucau gcugacuggg ggacuauuua cgccuuuauc ccccguccca 3360
acgagaagaa aagcaccgcu guaaagcaug uggccgugua cguucgguac aagaacgcgc 3420
gugccuggug ccccagcaug cuucccuuuc gcagcuacaa gcagaagaug cugaugcaau 3480
caggcgacgu cgagaccaac ccaggcccug cuucugacaa cccaaucuug gaauuucuug 3540
aagcagaaaa ugaucuaguc acucuggccu cucucuggaa gaugguacac ucuguucaac 3600
agaccuggag aaaguaugug aagaacgaca auuuuuggcc caauuuacuc agugaguuag 3660
ugggggaagg cuccaucgcc uuggccgcca cgcugucuaa ccaagcuuca guaaaagcuc 3720
ucuugggccu gcauuuucuc ucucgagggc ucaauuacac agacuuuuac ucuuuacuga 3780
uagagaaaug cucuaguuuc uuuacuguag aaccgccucc uccaccagcu gaaaaucuga 3840
ugaccaagcc cuccgugaag ucgaaauucc gaaagcuguu uaagaugcaa ggacccaugg 3900
acaaagucaa agacuggaac caaauagccg ccggcuugaa gaauuuucaa uuuguucgug 3960
accuagucaa agaggugguc gacuggcucc aggccuggau caacaaagag aaagccagcc 4020
cuguccucca guaccaguug gagaugaaga agcucgggcc cguggcuuug gcucaugaug 4080
ccuucauggc cgguuccggg cccccucuua gugacgacca gauugaauac cuccaaaacc 4140
ucaaaucucu ugcccuaaca cuggggaaga cuaauuuggc ccaaagucuc accacuauga 4200
ucaaugccaa gcaaaguucc gcccaacgag ucgaacccgu uguggugguc cucagaggca 4260
agccgggaug cggcaagagc uuggccucca cguugauugc ccaggcugug uccaagcguc 4320
ucuacggcuc acaaagugug uauucucuuc cuccggaccc agacuucuuc gacggauaca 4380
aaggacaguu uguaaccuug auggaugauu ugggacaaaa cccggauggg caagauuucu 4440
ccaccuuuug ucagauggug ucgaccgccc aauuucuucc caacauggcg gaccuugcag 4500
agaaggggcg ccccuuuacc uccaaucuua ucauugcaac uacaaaccuc ccccacuuca 4560
gcccugucac cauugcugau ccuucugcgg ucucucgucg gaucaacuac gacuugacuc 4620
uagaaguauc ugaggccuac aaaaagcaca cacggcugaa uuuugaccug gcuuucaggc 4680
gcacagacgc cccccccauu uauccuuuug cugcccaugu gccuuucgug gacguggcug 4740
ugcgcuucaa aaauggccac cagagcuuca aucuccuaga guuggucgac ucuauuugug 4800
cagacauucg agccaagcaa caaggugccc gaaauaugca gacucuaguu cuacagagcc 4860
cuaacgagaa ugaugacacc cccgucgacg aggcgcuggg uagaguucuc acucccgcug 4920
cggucgacga ggcgcuuguc gaccucgcuc aagaggccga uccgguuggc cgcuuggcua 4980
uucuugccaa acuaggucuu gcucuagcug cggucacccc cggcuugaua aucuuggcag 5040
ugggacucua uagguacuuc ucuggcucug augcagacca agaagaaacg gaaagugagg 5100
aaccugcuaa agcgccuagg agcgagaaug cuuaugacgg cccgaagaaa aacucuaagc 5160
ccccuggagc gcucucucuu auggaaaugc aacagcccaa cguggacaug ggcuuugagg 5220
cugcggucgc uaagaaagug gucgucccca uuacauucau gguucccaac agaccuucug 5280
gacuuacaca guccgcccuu cuuguggccg gccggaccuu ccuaauuaau gagcauacau 5340
gguccaaccc cuccuggacc aguuucacaa uccgugguga ggugcacacu cgugaugagc 5400
cuuuccaaac gguucauuuu acucaccaug guguucccac agaccugaug augguacguc 5460
ucggaccggg caacucuuuc ccuaacaauc uagacaaguu uggacuugac cagaugccgg 5520
cacguaacuc ccgugugguu ggcguuucgg cuaguuacgg uaauuucuuc uucucuggga 5580
auuuccuugg guuuguugac uccaucaccu cugaacaagg aacuuaugca agacuuuuua 5640
gguacagggu gaccaccuac aagggauggu gcgguucggc ccuggucugu gaggccggug 5700
guguccggcg caucauuggc cugcauucug cuggugccgc ugguaucggc gccgggaccu 5760
acaucucaaa auuaggacug aucaaagccc uuaaacaccu cggugaaccu cuggcuacaa 5820
ugcaaggacu gaugacugag cuagagccug gagucaccgu gcauguaccc cggaaaucua 5880
aauugagaaa gacgaccgca cacgcggugu acaaaccgga guuugaaccu gcuguguugu 5940
caaaauuuga ucccagacug aacaaggaug uugaccuaga ugagguaauu uggucuaaac 6000
acacugccaa cgucccuuau caaccuccuu uguucuacac auacauguca gaguacgcuc 6060
aucggguuuu cuccuuuuug ggaaaagaca augacauucu gaccguuaaa gaagcaaucc 6120
ugggcauccc uggacuagac ccuauggauc cccacacagc uccgggucug cccuacgcca 6180
uuagcggccu ucgacguacu gaucucgucg auuuugugaa cgguacggua gacgcagcac 6240
uggccaugca aauccagaaa uucuuagacg gugacuacuc ugaucauguc uuccaaacuu 6300
uucugaaaga ugaaaucaga cccucagaga agguccgagc gggaaaaacc cgcauugucg 6360
augugcccuc ccuggcacac ugcauugugg gcagaaugcu gcucgggcgu uucgccgcca 6420
aguuucaauc ccaucccggc uuucuucuug guucugcuau cggguccgac ccugaugucu 6480
ucuggaccgu cauaggggcu cagcucgagg gaagaaagaa cacguacgac guggacuaca 6540
gugccuuuga cucuucacac ggcacuggcu ccuucgaggc ucucaucucu cacuuuuuca 6600
ccguugacaa ugguuuuagc ccugcgcugg gaccguaucu cagaucccug gcugucucgg 6660
ugcacgcuua cggcgagcgu cgcaucaaga uuaccggagg ccuucccucu gguugugccg 6720
cgaccagccu ucugaucaca gugcucaaca augugaucau caggacugcu cuggcauuga 6780
cuuacaagga auuugaguau gacaugguug auaucaucgc cuacggugac gaccuuuugg 6840
uugguacgga uuaugaucug gacuucaaug aaguggcgcg gcgcgcugcc aaacuggggu 6900
auaagaugac uccugccaac aaggguuccg ucuucccucc gacuuccucu cucuccgaug 6960
cuguuuuucu aaaacgcaaa uucguccaaa acaaugacgg cuuauauaaa ccaguuaugg 7020
auuuaaagaa uuuggaagcc augcucuccu acuucaaacc aggaacacua cucgagaagc 7080
ugcaaucugu uucuauguug gcucaacauu cuggaaaaga agaauaugau agauugaugc 7140
gccccuucgc ugacuacggu gccguaccga gucacgagua ccugcaggca agauggaggg 7200
ccuuguucga uugaccuaga uagcccaacg cgcuucggug ccgccggcga uucugggaga 7260
acucagucgg aacagaaaag ggaaaaaaaa aaaaaaaaaa 7300
<210> 5
<211> 7286
<212> RNA
<213> 塞内卡病毒
<400> 5
uuugaaaugg ggggcugggc ccucaugccc aguccuuccu uuccccuucc gggggguaaa 60
ccggcugugu uugcuagagg cacagaggag caacauccaa ccugcucuug uggggaacgg 120
ugcggcucca auuccugcgu cgccaaaggu guuagcgcac ccaaacggcg caucuaccaa 180
ugcuauuggu guggucugcg aguucuagcc uacucguuuc uccccuaucc acucacucac 240
gcacaaaaag uguguuguaa cuacaagacu uagcccucgc acgagaugug cgauaaccgc 300
aagauugacu caagcgcgga aagcgcugua accacaugcu guuagucccu uuauggcugc 360
gagauggcua uccaccucgg aucacugaac uggagcucga cccuccuuag uaagggaacc 420
gagaggccuu cuugcaacaa gcuccgacac agaguccacg ugauugcuac caccaugagu 480
acaugguucu ccccucucga cccaggacuu cuuuuugaau auccacggcu cgauccagag 540
gguggggcau gaucccccua gcauagcgag cuacagcggg aacuguagcu aggccuuagc 600
gugcuuugga uacugccuga uagggcgacg gccuagucgu gucgguucua uagguagcac 660
auacaaauau gcagaacucu cauuuuucuu ucgauacagc cucuggcacc uuugaagacg 720
uaaccggaac aaaagucaag aucguugaau acccuagauc ggugaacaau gguguuuacg 780
auucguccac ucauuuagag auacugaacc uacaggguga aauugaaauu uuaaggucuu 840
ucaaugaaua ccaaauucgc gccgccaaac aacaacuugg acuggacauc guauaugaac 900
uacaggguaa uguucagaca accucaaaga augauuuuga uucccgcggc aauaauggua 960
acaugaccuu caauuacuac gcaaacacuu aucagaauuc aguagacuuc ucgaccuccu 1020
cgucggcguc aggcgccgga cccgggaacu cccggggcgg auuagcgggu cuccucacaa 1080
auuucagugg aaucuugaac ccucuuggcu accucaaaga ccacaauacc gaagaaaugg 1140
aaaacucugc ugaucgaguc auaacacaaa cggcgggcaa cacugccaua aacacgcaau 1200
caucacuggg uguguugugu gccuacguug aagacccgac caaaucugac ccuccgucca 1260
gcagcacaga ucaacccacc accacuuuua cugccaucga caggugguac acuggacgcc 1320
ucaauucuug gacaaaagcu guaaaaaccu ucucuuuuca ggccgucccg cucccuggag 1380
ccuuccuguc uagacaggga ggccucaaug gaggggccuu cacggcuacc cuacauagac 1440
auuucuuaau gaagugcggg uggcaggugc agguccaaug caauuugaca caauuccacc 1500
aaggugcucu ucuuguugcc augguccccg aaaccacccu ugaugucaag cccgacggca 1560
aggcaaagag ccuacaggag cugaaugaag agcagugggu agaaaugucu gacgauuacc 1620
ggaccgggaa aaacaugccu uuucagucuc uuggcacaua cuaucggccc ccuaacugga 1680
cuuggggccc uaauuucauc aaccccuauc aaguaacagu uuucccacac caaauucuga 1740
acgcgagaac cucuaccucg guagacauaa gugucccaua caucggggag acuccuacac 1800
aauccucaga gacacagaac uccuggaccc uccucguuau ggugcuuguc ccccuggacu 1860
acaaggaggg agccacaacu gacccagaaa uuacauuuuc cguaaggccu acaaguccuu 1920
acuucaaugg gcuucguaac cgcuacacga ccgggacgga cgaggaacag gggcccauuc 1980
ccacagcacc cagagaaaau ucgcuuaugu uucucucgac caucccugac gacacugucc 2040
cugcuuacgg gaaugugcgu accccucccg ucaauuaccu uccuggugaa auaaccgacc 2100
ucuuacaacu ggcccguaua cccacucuca uggcguuugg gcgggugccu gaaccugaac 2160
cugccucaga cgcuuaugug cccuacguug ccguucccac ccaguucgau gacaagccuc 2220
ucaucuccuu cccgaucacc cuuucagauc cugucuacca gaauacucug guaggcgcca 2280
ucaguucaaa uuucgccaac uaccgggggu guauccaaau cacucugaca uuuuguggac 2340
cuaugauggc aagagggaaa uuccuacucu cguauucucc cccaaaugga acacaaccac 2400
agacccuuuc ugaagccaug cagugcacau auucuauuug ggauauaggc uuaaacucua 2460
guuggaccuu ugucaucccc uacaucucgc ccagugacua ccgugaaacu cgggccauua 2520
ccaauucggu uuauucugcu gauggcuggu uuagccugca caagcugacc aaaauuacuc 2580
uaccaccuga uugcccacag agccccugua uucucuuuuu cgccucugcu ggugaggauu 2640
acacccuccg ucuccccguu gauuguaauc cuucuuaugu guuccacucc accgacaacg 2700
ccgagacugg gguuauugag gcggguaaca cugacaccga uuucucuggu gaauuggcgg 2760
cuccuggcuc uaaccacacu aaugucaagu uccuguuuga ccgaucucga uuacugaaug 2820
uaauuaaggu acuggagaag gacgccgucu ucccccgccc uuuccccaca gcaacuggua 2880
cacaacagga cgaugguuac uuuugucuuc uaacaccccg cccaacaguc gccucccgac 2940
ccgccacucg uuucggccug uacgucaguc cgucugacag uggcguucuc gccaacacuu 3000
cacuggauuu caauuuuuac agcuuggccu guuucacuua cuuuagauca gaccuugaag 3060
ucacgguggu cucacuggag ccagaucugg aauucgcugu agggugguuc cccucuggca 3120
gugaguacca ggcuuccagc uuugucuacg accaacugca uguacccuac cacuuuacug 3180
ggcgcacucc ccgcgcuuuc gccagcaagg gugggaaggu aucuuucgug cucccuugga 3240
acucugucuc auccgugcuu cccgugcgcu gggggggcgc uuccaagcuu ucuucugcca 3300
cgcggggucu gccggcucau gcugacuggg ggacuauuua cgccuuuauc ccccguccca 3360
acgagaagaa aagcaccgcu guaaagcaug uggccgugua cguucgguac aagaacgcgc 3420
gugccuggug ccccagcaug cuucccuuuc gcagcuacaa gcagaagaug cugaugcaau 3480
caggcgacgu cgagaccaac ccaggcccug cuucugacaa cccaaucuug gaauuucuug 3540
aagcagaaaa ugaucuaguc acucuggccu cucucuggaa gaugguacac ucuguucaac 3600
agaccuggag aaaguaugug aagaacgaca auuuuuggcc caauuuacuc agugaguuag 3660
ugggggaagg cuccaucgcc uuggccgcca cgcugucuaa ccaagcuuca guaaaagcuc 3720
ucuugggccu gcauuuucuc ucucgagggc ucaauuacac agacuuuuac ucuuuacuga 3780
uagagaaaug cucuaguuuc uuuacuguag aaccgccucc uccaccagcu gaaaaucuga 3840
ugaccaagcc cuccgugaag ucgaaauucc gaaagcuguu uaagaugcaa ggacccaugg 3900
acaaagucaa agacuggaac caaauagccg ccggcuugaa gaauuuucaa uuuguucgug 3960
accuagucaa agaggugguc gacuggcucc aggccuggau caacaaagag aaagccagcc 4020
cuguccucca guaccaguug gagaugaaga agcucgggcc cguggcuuug gcucaugaug 4080
ccuucauggc cgguuccggg cccccucuua gugacgacca gauugaauac cuccaaaacc 4140
ucaaaucucu ugcccuaaca cuggggaaga cuaauuuggc ccaaagucuc accacuauga 4200
ucaaugccaa gcaaaguucc gcccaacgag ucgaacccgu uguggugguc cucagaggca 4260
agccgggaug cggcaagagc uuggccucca cguugauugc ccaggcugug uccaagcguc 4320
ucuacggcuc acaaagugug uauucucuuc cuccggaccc agacuucuuc gacggauaca 4380
aaggacaguu uguaaccuug auggaugauu ugggacaaaa cccggauggg caagauuucu 4440
ccaccuuuug ucagauggug ucgaccgccc aauuucuucc caacauggcg gaccuugcag 4500
agaaggggcg ccccuuuacc uccaaucuua ucauugcaac uacaaaccuc ccccacuuca 4560
gcccugucac cauugcugau ccuucugcgg ucucucgucg gaucaacuac gacuugacuc 4620
uagaaguauc ugaggccuac aaaaagcaca cacggcugaa uuuugaccug gcuuucaggc 4680
gcacagacgc cccccccauu uauccuuuug cugcccaugu gccuuucgug gacguggcug 4740
ugcgcuucaa aaauggccac cagagcuuca aucuccuaga guuggucgac ucuauuugug 4800
cagacauucg agccaagcaa caaggugccc gaaauaugca gacucuaguu cuacagagcc 4860
cuaacgagaa ugaugacacc cccgucgacg aggcgcuggg uagaguucuc acucccgcug 4920
cggucgacga ggcgcuuguc gaccucgcuc aagaggccga uccgguuggc cgcuuggcua 4980
uucuugccaa acuaggucuu gcucuagcug cggucacccc cggcuugaua aucuuggcag 5040
ugggacucua uagguacuuc ucuggcucug augcagacca agaagaaacg gaaagugagg 5100
aaccugcuaa agcgccuagg agcgagaaug cuuaugacgg cccgaagaaa aacucuaagc 5160
ccccuggagc gcucucucuu auggaaaugc aacagcccaa cguggacaug ggcuuugagg 5220
cugcggucgc uaagaaagug gucgucccca uuacauucau gguucccaac agaccuucug 5280
gacuuacaca guccgcccuu cuuguggccg gccggaccuu ccuaauuaau gagcauacau 5340
gguccaaccc cuccuggacc aguuucacaa uccgugguga ggugcacacu cgugaugagc 5400
cuuuccaaac gguucauuuu acucaccaug guguucccac agaccugaug augguacguc 5460
ucggaccggg caacucuuuc ccuaacaauc uagacaaguu uggacuugac cagaugccgg 5520
cacguaacuc ccgugugguu ggcguuucgg cuaguuacgg uaauuucuuc uucucuggga 5580
auuuccuugg guuuguugac uccaucaccu cugaacaagg aacuuaugca agacuuuuua 5640
gguacagggu gaccaccuac aagggauggu gcgguucggc ccuggucugu gaggccggug 5700
guguccggcg caucauuggc cugcauucug cuggugccgc ugguaucggc gccgggaccu 5760
acaucucaaa auuaggacug aucaaagccc uuaaacaccu cggugaaccu cuggcuacaa 5820
ugcaaggacu gaugacugag cuagagccug gagucaccgu gcauguaccc cggaaaucua 5880
aauugagaaa gacgaccgca cacgcggugu acaaaccgga guuugaaccu gcuguguugu 5940
caaaauuuga ucccagacug aacaaggaug uugaccuaga ugagguaauu uggucuaaac 6000
acacugccaa cgucccuuau caaccuccuu uguucuacac auacauguca gaguacgcuc 6060
aucggguuuu cuccuuuuug ggaaaagaca augacauucu gaccguuaaa gaagcaaucc 6120
ugggcauccc uggacuagac ccuauggauc cccacacagc uccgggucug cccuacgcca 6180
uuagcggccu ucgacguacu gaucucgucg auuuugugaa cgguacggua gacgcagcac 6240
uggccaugca aauccagaaa uucuuagacg gugacuacuc ugaucauguc uuccaaacuu 6300
uucugaaaga ugaaaucaga cccucagaga agguccgagc gggaaaaacc cgcauugucg 6360
augugcccuc ccuggcacac ugcauugugg gcagaaugcu gcucgggcgu uucgccgcca 6420
aguuucaauc ccaucccggc uuucuucuug guucugcuau cggguccgac ccugaugucu 6480
ucuggaccgu cauaggggcu cagcucgagg gaagaaagaa cacguacgac guggacuaca 6540
gugccuuuga cucuucacac ggcacuggcu ccuucgaggc ucucaucucu cacuuuuuca 6600
ccguugacaa ugguuuuagc ccugcgcugg gaccguaucu cagaucccug gcugucucgg 6660
ugcacgcuua cggcgagcgu cgcaucaaga uuaccggagg ccuucccucu gguugugccg 6720
cgaccagccu ucugaacaca gugcucaaca augugaucau caggacugcu cuggcauuga 6780
cuuacaagga auuugaguau gacaugguug auaucaucgc cuacggugac gaccuuuugg 6840
uugguacgga uuaugaucug gacuucaaug aaguggcgcg gcgcgcugcc aaacuggggu 6900
auaagaugac uccugccaac aaggguuccg ucuucccucc gacuuccucu cucuccgaug 6960
cuguuuuucu aaaacgcaaa uucguccaaa acaaugacgg cuuauauaaa ccaguuaugg 7020
auuuaaagaa uuuggaagcc augcucuccu acuucaaacc aggaacacua cucgagaagc 7080
ugcaaucugu uucuauguug gcucaacauu cuggaaaaga agaauaugau agauugaugc 7140
accccuucgc ugacuacggu gccguaccga gucacgagua ccugcaggca agauggaggg 7200
ccuuguucga uugaccuaga uagcccaacg cgcuucggug ccgccggcga uucugggaga 7260
acucagucgg aacagaaaag ggaaaa 7286
<210> 6
<211> 7270
<212> RNA
<213> 塞内卡病毒
<400> 6
cugggcccuc augcccaguc cuuccuuucc ccuuccgggg gguaaaccgg cuguguuugc 60
uagaggcaca gaggagcaac auccaaccug cuuuuguggg gaacggugcg gcuccaauuc 120
cugcgucgcc aaagguguua gcgcacccaa acggcgcauc uaccaaugcu auuggugugg 180
ucugcgaguu cuagccuacu cguuucuccc cuauccacuc acucacgcac aaaaagugug 240
cuguaauuac aagauuuagc ccucgcacga gaugugcgau aaccgcaaga uugacucaag 300
cgcggaaagc gcuguaacca caugcuguua gucccuucau ggcugcgaga uggcuaucca 360
ccucggauca cugaacugga gcucgacccu ccuuaguaag ggaaccgaga ggccuucuug 420
caacaagcuc cgacacagag uccacgugau ugcuaccacc augaguacau gguucucccc 480
ucucgaccca ggacuucuuu uugaauaucc acggcucgau ccagagggug gggcaugauc 540
ccccuagcau agcgagcuac agcgggaacu guagcuaggc cuuagcgugc cuuggauacu 600
gccugauagg gcgacggccu agucgugucg guucuauagg uagcacauac aaauaugcag 660
aacucucacu uuucuuucga uacagccucu ggcaccuuug aagacguaac cggaacaaaa 720
gucaagaucg uugaauaccc uagaucggug aacaauggug uuuacgauuc guccacucau 780
uuagagauac ugaaccuaca gggugaaauu gaaauuuuaa agucuuucaa ugaauaccaa 840
auucgcgccg ccaaacaaca acuuggacug gacaucguau acgaacuaca ggguaauguu 900
cagacaaccu caaagaauga uuuugauucc cgcgguaaua augguaacau gaccuucaau 960
uacuacgcaa acacuuacca gaauucagua gacuucucga ccuccucguc ggcgucaggc 1020
gccggacccg ggaacucccg gggcggauua gcgggucucc ucacaaauuu caguggaauc 1080
uugaacccuc uuggcuaccu caaagaucac aauaccgaag aaauggaaaa cucugcugau 1140
cgagucauaa cgcaaacggc gggcaacacu gccauaaaca cgcaaucauc acugggugug 1200
uugugugccu acguugaaga cccgaccaaa ucugacccuc cguccagcag cacagaucaa 1260
cccaccacca cuuuuacugc caucgacagg ugguacacug gacgccucaa uucuuggaca 1320
aaagcuguaa aaaccuucuc uuuucaggcc gucccgcucc cuggagccuu ccugucuaga 1380
cagggaggcc ucaacggagg ggccuucacg gcuacccuac auagacauuu cuuaaugaag 1440
ugcggguggc aggugcaggu ccaaugcaau uugacgcaau uccaccaagg ugcucuucuu 1500
guugccaugg uccccgaaac cacccuugau gucaaaccug acggcaaggc aaagagcuua 1560
caggagcuga augaagaaca guggguggaa augucugacg auuaccggac cgggaaaaac 1620
augccuuucc agucucuugg cacauacuau cggcccccua acuggacuug gggccccaau 1680
uucaucaacc ccuaucaagu aacaguuuuc ccacaccaaa uucugaacgc gagaaccucu 1740
accucgguag acauaagugu cccauacauc ggggagacuc cuacacaauc cucagagaca 1800
cagaacuccu ggacccuccu cguuauggug cuuguccccc uggacuacaa ggagggagcc 1860
acaacugacc cagaaauuac auuuucugua aggccuacaa guccuuacuu caaugggcua 1920
cguaaccguu ucacgaccgg gacggacgag gaacaggggc ccauucccac agcacccaga 1980
gaaaauucgc uuauguuucu cucaaccauc ccugacgaca cugucccugc uuacgggaau 2040
gugcguaccc cucccgucaa uuaccucccu ggugaaauaa ccgaccucuu acaacuggcc 2100
cguauaccca cucucauggc guucgggcgg gugucugaac ccgagccugc cucagacaca 2160
uaugugcccu acguugccgu uccugcccag uucgacgaca agccucucau cuccuucccg 2220
aucacccuuu cagauccugu cuaccagaac acccugguag gcgccaucag uucgaauuuc 2280
gccaacuacc ggggguguau ccaaaucacu cugacauuuu guggacccau gauggcaaga 2340
gggaaauucc uacucucgua uucuccucca aauggagcac aaccacagac ccuuucugaa 2400
gcuaugcagu gcacguacuc uauuugggau auaggcuuga acucuaguug gaccuuuguc 2460
auccccuaca ucucgcccag ugauuaccgu gaaacucggg cuauuaccaa cucaguuuau 2520
ucugcugaug guugguuuag ccugcacaag cugacuaaaa uuacucuacc accugacugc 2580
ccacagaguc ccuguauucu cuuuuucgcc ucugcuggug aggauuacac ccuccgucuc 2640
ccuguugauu guaauccuuc cuacguguuc cacuccaccg acaacgccga gacugggguu 2700
auugaggcgg guaacacuga caccgacuuc ucuggugagc uggcggcucc uggcucuaac 2760
cacacuaaug ucaaguuccu guuugaucga ucucgauuac ugaauguaau uaagguacug 2820
gagaaggacg ccgucuuccc ccguccuuuc cccacagcaa caggugcaca gcaggacgau 2880
gguuacuuuu gccuucuaac accccgccca acagucgcuu cccgacccgc cacucguuuc 2940
ggccuguacg ucaauccguc ugacaguggc guucucgcua acacuucacu ggauuucaau 3000
uuuuacagcu uggccuguuu cacuuacuuu agaucagacc uugaagucac gguggucuca 3060
cuggagccag aucuggaauu cgcuguaggg ugguuccccu cuggcaguga guaccaggcu 3120
uccagcuuug ucuacgacca acugcaugua cccuaccacu uuacugggcg cacuccccgc 3180
gcuuucacca gcaagggugg aaagguaucu uucgugcuuc cuuggaacuc ugucucaucc 3240
gugcuucccg ugcgcugggg gggcgcuucc aagcuuucuu ccgccacgcg gggucuaccg 3300
gcucaugcug acugggggac cauuuacgcc uucauccccc guccuaauga gaagaaaagc 3360
accgcugcaa agcacguggc gguguacguu cgguacaaga acgcgcgugc cuggugcccc 3420
agcaugcucc ccuuccgcag cuacaagcag aagaugcuga ugcaaucagg cgacgucgag 3480
accaacccug gcccugcuuc ugacaaccca aucuuggagu uucuugaagc ugaaaacgau 3540
cuagucacuc uggccucucu cuggaagaug guacacucug uucaacagac cuggagaaag 3600
uaugugaaga augacaauuu uuggcccaau uugcucagug agcuaguggg ggaaggcucc 3660
aucgccuugg ccgccacgcu aucuaaccaa gcuucaguaa aagcucucuu aggccugcau 3720
uuucucuccc gagggcucaa uuauacagau uuuuacucuu uacugauaga gaaaugcucu 3780
aguuucuuua cuguagaacc gccuccucca ccagcugaaa aucugaugac caagcccucc 3840
gugaggucga aauuccgaaa gcuguuuaag augcaaggac ccauggacac agucaaagac 3900
uggaaccaaa uagccgccgg ccugaagaau uuccaauuug uucgugaccu ggucaaagag 3960
guggucgauu ggcuccaggc cuggauuaau aaagagaaag ccagcccugu ccuccaguac 4020
cagcuggaga ugaagaaacu cggacccgug gcuuuggcuc augaugccuu cauggccggu 4080
uccgggcccc cucuuaguga cgaccagauu gaauaucucc agaaccucaa aucucuugcc 4140
cuaacacugg ggaagacuaa uuuggcccaa agucucacca cuaugaucaa ugccaagcaa 4200
agcuccgcuc aacgagucga acccguugug gugguccuua gaggcaagcc gggauguggc 4260
aagagcuugg ccuccacguu gauugcccag gcugugucca agcgucucua cggcucacaa 4320
aguguguauu cucuuccucc ggauccagac uucuucgacg gauacaaagg acaguuugua 4380
accuugaugg acgaucuggg acaaaacccg gaugggcaag auuucuccac cuuuugucag 4440
auggugucga ccgcccaauu ucuucccaac auggcggacc uuacagagaa ggggcguccc 4500
uucaccucca aucuuaucau ugcaacuaca aaccucccuc acuucagccc ugucaccauu 4560
gcugauccuu cugcagucuc ucgucguauc aacuacgacc ugacucuaga aguaucugag 4620
gccuauaaga agcacacacg gcugaauuuu gaccuggcuu ucagacgcac agacgccccc 4680
cccauuuauc cuuuugcugc ccaugugccc uucguggacg uggcugugcg cuucaaaaau 4740
ggucaucaga gcuucaaucu ccuagaguug gucgacucua uuugugcaga cauucgagcc 4800
aagcaacaag gugcccgaaa uaugcagacu cugguucuac agagccccaa cgagaacgac 4860
gacacccccg ucgacgaggc guuggguaga guucucaccc ccgcugcggu cgacgaggcg 4920
cuugucgacc ucgcuccaga ugccgacccg guuggccguu uggcuauucu cgccaagcua 4980
ggucuugccc uagcugcggu caccccuggu uugauaaucu uggcaguggg acucuacagg 5040
uacuucucug gcucugauac agaccaagaa gaaacagaag gugaggagcc ugcuaaagcg 5100
ccuaggagcg agaaugcuua ugacggcccg aagaaaaacu cuaagccccc uggagcgcuc 5160
ucccuuaugg aaaugcaaca gcccaacgug gacaugggcu uugaggcugc ggucgcuaag 5220
aaaguggucg uccccauuac cuucaugguu cccaacagac cuucuggacu uacacagucc 5280
gcucuucuug uggccggccg gaccuuccua auuaaugagc auacaugguc caaccccucc 5340
uggaccagcu ucacaauccg uggugaggug cacacccgug augagccuuu ccaaacgguu 5400
cauuuuacuc accauggugu ucccacagau cuggugaugg uacgucucgg accgggcaac 5460
uccuucccua acaaucuaga caaguuugga cuugaucaga ugccggcacg uaacucccgu 5520
gugguuggcg uuucggcuag uuacggcaac uucuucuucu cugggaacuu ccucggguuu 5580
guugacucca ucaccucuga ccaaggaacu uaugcgagac uuuuuaggua cagggugacg 5640
accuacaagg gguggugcgg uucggcccug guuugugagg ccgguggugu ccggcgcauc 5700
auuggccugc auucugcugg ugccgcuggu aucggcgccg ggacuuacau cucaaaauua 5760
ggacugauca aagcccucaa acaccucggu gaaccucugg cuacaaugca aggacugaug 5820
acugagcuag agccuggagu caccgugcau guaccccgga aaucuaaauu gagaaagacg 5880
accgcacacg cgguguacaa accggaguuu gaaccugcug uguugucaaa auuugauccc 5940
agacugaaca aggauguuga ccuagaugag guaauuuggu cuaaacacac ugccaacguc 6000
ccuuaucaac cuccuuuguu cuacacauac augucagagu acgcucaucg gguuuucucc 6060
uuuuugggaa aagacaauga cauucugacc gucaaagaag caaucuuggg aaucccugga 6120
cuagacccua uggaucccca cacagcuccg ggucugcccu acgccauuag cggccuucga 6180
cguacugauc ucgucgauuu ugcgaacggc acgguggacc cgacacuggc cguacaaauc 6240
caaaaauucu uagacgguga cuacucugau caugucuucc aaacuuuucu gaaagaugaa 6300
aucagacccu cagagaaggu ccgagcggga aaaacccgca uugucgaugu gcccucccug 6360
gcgcacugca uugugggcag aauguugcuu gggcgcuuug ccgccaaguu ucaaucccau 6420
ccuggcuuuc uccuuggcuc ugcuaucggg ucugacccug augucuucug gaccgucaua 6480
ggggcucagc ucgagggaag aaagaacacg uaugacgugg acuacagugc cuuugacucu 6540
ucacacggca cuggcuccuu cgaggcucuc aucucucacu uuuucaccgu ggacaauggu 6600
uuuagcccug cgcugggauc guaucucaga ucccuggcug ucucggugca cgcuuacggc 6660
gagcgucgca ucaagauuac cggaggccuc cccucugguu gugccgcgac cagccugcug 6720
aacacagugc ucaacaaugu gaucaucagg acugcucugg cauugaccua caaggaauuu 6780
gaauaugaca ugguugauau caucgccuac ggugacgacc uucugguugg uacggauuac 6840
gaucuggacu ucaaugaggu ggcgcggcgc gcugccaaac ugggguauaa gaugacuccu 6900
gccaacaaag guucugucuu cccuccgacu uccucucucu ccgacgcugu uuuucuaaaa 6960
cgcaaauucg uccaaaacaa ugacggcuua uacaaaccag uuauggauuu aaagaauuug 7020
gaagccaugc ucuccuacuu caaaccagga acacuacucg agaagcugca aucuguuucu 7080
auguuggcuc aacauucugg aaaagaagaa uaugauagau ugaugcaccc cuuugcugac 7140
uacggugccg uaccgaguca cgaguaccug caggcaagau ggagggccuu guucgacuga 7200
ccuagauagc ccaacgcgcu ccggugcugc cggcgauucu gggagaacuc agucggaaca 7260
gaaaagggaa 7270
<210> 7
<211> 7270
<212> RNA
<213> 塞内卡病毒
<400> 7
cugggcccuc augcccaguc cuuccuuucc ccuuccgggg gguaaaccgg cuguguuugc 60
uagaggcaca gaggagcaac auccaaccug cuuuuguggg gaacggugcg gcuccaauuc 120
cugcgucgcc aaagguguua gcgcacccaa acggcgcauc uaccaaugcu auuggugugg 180
ucugcgaguu cuagccuacu cguuucuccc cuauccacuc acucacgcac aaaaagugug 240
cuguaauuac aagauuuagc ccucgcacga gaugugcgau aaccgcaaga uugacucaag 300
cgcggaaagc gcuguaacca caugcuguua gucccuucau ggcugcgaga uggcuaucca 360
ccucggauca cugaacugga gcucgacccu ccuuaguaag ggaaccgaga ggccuucuug 420
caacaagcuc cgacacagag uccacgugau ugcuaccacc augaguacau gguucucccc 480
ucucgaccca ggacuucuuu uugaauaucc acggcucgau ccagagggug gggcaugauc 540
ccccuagcau agcgagcuac agcgggaacu guagcuaggc cuuagcgugc cuuggauacu 600
gccugauagg gcgacggccu agucgugucg guucuauagg uagcacauac aaauaugcag 660
aacucucacu uuucuuucga uacagccucu ggcaccuuug aagacguaac cggaacaaaa 720
gucaagaucg uugaauaccc uagaucggug aacaauggug uuuacgauuc guccacucau 780
uuagagauac ugaaccuaca gggugaaauu gaaauuuuaa agucuuucaa ugaauaccaa 840
auucgcgccg ccaaacaaca acuuggacug gacaucguau acgaacuaca ggguaauguu 900
cagacaaccu caaagaauga uuuugauucc cgcgguaaua augguaacau gaccuucaau 960
uacuacgcaa acacuuacca gaauucagua gacuucucga ccuccucguc ggcgucaggc 1020
gccggacccg ggaacucccg gggcggauua gcgggucucc ucacaaauuu caguggaauc 1080
uugaacccuc uuggcuaccu caaagaucac aauaccgaag aaauggaaaa cucugcugau 1140
cgagucauaa cgcaaacggc gggcaacacu gccauaaaca cgcaaucauc acugggugug 1200
uugugugccu acguugaaga cccgaccaaa ucugacccuc cguccagcag cacagaucaa 1260
cccaccacca cuuuuacugc caucgacagg ugguacacug gacgccucaa uucuuggaca 1320
aaagcuguaa aaaccuucuc uuuucaggcc gucccgcucc cuggagccuu ccugucuaga 1380
cagggaggcc ucaacggagg ggccuucacg gcuacccuac auagacauuu cuuaaugaag 1440
ugcggguggc aggugcaggu ccaaugcaau uugacgcaau uccaccaagg ugcucuucuu 1500
guugccaugg uccccgaaac cacccuugau gucaaaccug acggcaaggc aaagagcuua 1560
caggagcuga augaagaaca guggguggaa augucugacg auuaccggac cgggaaaaac 1620
augccuuucc agucucuugg cacauacuau cggcccccua acuggacuug gggccccaau 1680
uucaucaacc ccuaucaagu aacaguuuuc ccacaccaaa uucugaacgc gagaaccucu 1740
accucgguag acauaagugu cccauacauc ggggagacuc cuacacaauc cucagagaca 1800
cagaacuccu ggacccuccu cguuauggug cuuguccccc uggacuacaa ggagggagcc 1860
acaacugacc cagaaauuac auuuucugua aggccuacaa guccuuacuu caaugggcua 1920
cguaaccguu ucacgaccgg gacggacgag gaacaggggc ccauucccac agcacccaga 1980
gaaaauucgc uuauguuucu cucaaccauc ccugacgaca cugucccugc uuacgggaau 2040
gugcguaccc cucccgucaa uuaccucccu ggugaaauaa ccgaccucuu acaacuggcc 2100
cguauaccca cucucauggc guucgggcgg gugucugaac ccgagccugc cucagacaca 2160
uaugugcccu acguugccgu uccugcccag uucgacgaca agccucucau cuccuucccg 2220
aucacccuuu cagauccugu cuaccagaac acccugguag gcgccaucag uucgaauuuc 2280
gccaacuacc ggggguguau ccaaaucacu cugacauuuu guggacccau gauggcaaga 2340
gggaaauucc uacucucgua uucuccucca aauggagcac aaccacagac ccuuucugaa 2400
gcuaugcagu gcacguacuc uauuugggau auaggcuuga acucuaguug gaccuuuguc 2460
auccccuaca ucucgcccag ugauuaccgu gaaacucggg cuauuaccaa cucaguuuau 2520
ucugcugaug guugguuuag ccugcacaag cugacuaaaa uuacucuacc accugacugc 2580
ccacagaguc ccuguauucu cuuuuucgcc ucugcuggug aggauuacac ccuccgucuc 2640
ccuguugauu guaauccuuc cuacguguuc cacuccaccg acaacgccga gacugggguu 2700
auugaggcgg guaacacuga caccgacuuc ucuggugagc uggcggcucc uggcucuaac 2760
cacacuaaug ucaaguuccu guuugaucga ucucgauuac ugaauguaau uaagguacug 2820
gagaaggacg ccgucuuccc ccguccuuuc cccacagcaa caggugcaca gcaggacgau 2880
gguuacuuuu gccuucuaac accccgccca acagucgcuu cccgacccgc cacucguuuc 2940
ggccuguacg ucaauccguc ugacaguggc guucucgcua acacuucacu ggauuucaau 3000
uuuuacagcu uggccuguuu cacuuacuuu agaucagacc uugaagucac gguggucuca 3060
cuggagccag aucuggaauu cgcuguaggg ugguuccccu cuggcaguga guaccaggcu 3120
uccagcuuug ucuacgacca acugcaugua cccuaccacu uuacugggcg cacuccccgc 3180
gcuuucacca gcaagggugg aaagguaucu uucgugcuuc cuuggaacuc ugucucaucc 3240
gugcuucccg ugcgcugggg gggcgcuucc aagcuuucuu ccgccacgcg gggucuaccg 3300
gcucaugcug acugggggac cauuuacgcc uucauccccc guccuaauga gaagaaaagc 3360
accgcugcaa agcacguggc gguguacguu cgguacaaga acgcgcgugc cuggugcccc 3420
agcaugcucc ccuuccgcag cuacaagcag aagaugcuga ugcaaucagg cgacgucgag 3480
accaacccug gcccugcuuc ugacaaccca aucuuggagu uucuugaagc ugaaaacgau 3540
cuagucacuc uggccucucu cuggaagaug guacacucug uucaacagac cuggagaaag 3600
uaugugaaga augacaauuu uuggcccaau uugcucagug agcuaguggg ggaaggcucc 3660
aucgccuugg ccgccacgcu aucuaaccaa gcuucaguaa aagcucucuu aggccugcau 3720
uuucucuccc gagggcucaa uuauacagau uuuuacucuu uacugauaga gaaaugcucu 3780
aguuucuuua cuguagaacc gccuccucca ccagcugaaa aucugaugac caagcccucc 3840
gugaggucga aauuccgaaa gcuguuuaag augcaaggac ccauggacac agucaaagac 3900
uggaaccaaa uagccgccgg ccugaagaau uuccaauuug uucgugaccu ggucaaagag 3960
guggucgauu ggcuccaggc cuggauuaau aaagagaaag ccagcccugu ccuccaguac 4020
cagcuggaga ugaagaaacu cggacccgug gcuuuggcuc augaugccuu cauggccggu 4080
uccgggcccc cucuuaguga cgaccagauu gaauaucucc agaaccucaa aucucuugcc 4140
cuaacacugg ggaagacuaa uuuggcccaa agucucacca cuaugaucaa ugccaagcaa 4200
agcuccgcuc aacgagucga acccguugug gugguccuua gaggcaagcc gggauguggc 4260
aagagcuugg ccuccacguu gauugcccag gcugugucca agcgucucua cggcucacaa 4320
aguguguauu cucuuccucc ggauccagac uucuucgacg gauacaaagg acaguuugua 4380
accuugaugg acgaucuggg acaaaacccg gaugggcaag auuucuccac cuuuugucag 4440
auggugucga ccgcccaauu ucuucccaac auggcggacc uuacagagaa ggggcguccc 4500
uucaccucca aucuuaucau ugcaacuaca aaccucccuc acuucagccc ugucaccauu 4560
gcugauccuu cugcagucuc ucgucguauc aacuacgacc ugacucuaga aguaucugag 4620
gccuauaaga agcacacacg gcugaauuuu gaccuggcuu ucagacgcac agacgccccc 4680
cccauuuauc cuuuugcugc ccaugugccc uucguggacg uggcugugcg cuucaaaaau 4740
ggucaucaga gcuucaaucu ccuagaguug gucgacucua uuugugcaga cauucgagcc 4800
aagcaacaag gugcccgaaa uaugcagacu cugguucuac agagccccaa cgagaacgac 4860
gacacccccg ucgacgaggc guuggguaga guucucaccc ccgcugcggu cgacgaggcg 4920
cuugucgacc ucgcuccaga ugccgacccg guuggccguu uggcuauucu cgccaagcua 4980
ggucuugccc uagcugcggu caccccuggu uugauaaucu uggcaguggg acucuacagg 5040
uacuucucug gcucugauac agaccaagaa gaaacagaag gugaggagcc ugcuaaagcg 5100
ccuaggagcg agaaugcuua ugacggcccg aagaaaaacu cuaagccccc uggagcgcuc 5160
ucccuuaugg aaaugcaaca gcccaacgug gacaugggcu uugaggcugc ggucgcuaag 5220
aaaguggucg uccccauuac cuucaugguu cccaacagac cuucuggacu uacacagucc 5280
gcucuucuug uggccggccg gaccuuccua auuaaugagc auacaugguc caaccccucc 5340
uggaccagcu ucacaauccg uggugaggug cacacccgug augagccuuu ccaaacgguu 5400
cauuuuacuc accauggugu ucccacagau cuggugaugg uacgucucgg accgggcaac 5460
uccuucccua acaaucuaga caaguuugga cuugaucaga ugccggcacg uaacucccgu 5520
gugguuggcg uuucggcuag uuacggcaac uucuucuucu cugggaacuu ccucggguuu 5580
guugacucca ucaccucuga ccaaggaacu uaugcgagac uuuuuaggua cagggugacg 5640
accuacaagg gguggugcgg uucggcccug guuugugagg ccgguggugu ccggcgcauc 5700
auuggccugc auucugcugg ugccgcuggu aucggcgccg ggacuuacau cucaaaauua 5760
ggacugauca aagcccucaa acaccucggu gaaccucugg cuacaaugca aggacugaug 5820
acugagcuag agccuggagu caccgugcau guaccccgga aaucuaaauu gagaaagacg 5880
accgcacacg cgguguacaa accggaguuu gaaccugcug uguugucaaa auuugauccc 5940
agacugaaca aggauguuga ccuagaugag guaauuuggu cuaaacacac ugccaacguc 6000
ccuuaucaac cuccuuuguu cuacacauac augucagagu acgcucaucg gguuuucucc 6060
uuuuugggaa aagacaauga cauucugacc gucaaagaag caaucuuggg aaucccugga 6120
cuagacccua uggaucccca cacagcuccg ggucugcccu acgccauuag cggccuucga 6180
cguacugauc ucgucgauuu ugcgaacggc acgguggacc cgacacuggc cguacaaauc 6240
caaaaauucu uagacgguga cuacucugau caugucuucc aaacuuuucu gaaagaugaa 6300
aucagacccu cagagaaggu ccgagcggga aaaacccgca uugucgaugu gcccucccug 6360
gcgcacugca uugugggcag aauguugcuu gggcgcuuug ccgccaaguu ucaaucccau 6420
ccuggcuuuc uccuuggcuc ugcuaucggg ucugacccug augucuucug gaccgucaua 6480
ggggcucagc ucgagggaag aaagaacacg uaugacgugg acuacagugc cuuugacucu 6540
ucacacggca cuggcuccuu cgaggcucuc aucucucacu uuuucaccgu ggacaauggu 6600
uuuagcccug cgcugggauc guaucucaga ucccuggcug ucucggugca cgcuuacggc 6660
gagcgucgca ucaagauuac cggaggccuc cccucugguu gugccgcgac cagccugcug 6720
aacacagugc ucaacaaugu gaucaucagg acugcucugg cauugaccua caaggaauuu 6780
gaauaugaca ugguugauau caucgccuac ggugacgacc uucugguugg uacggauuac 6840
gaucuggacu ucaaugaggu ggcgcggcgc gcugccaaac ugggguauaa gaugacuccu 6900
gccaacaaag guucugucuu cccuccgacu uccucucucu ccgacgcugu uuuucuaaaa 6960
cgcaaauucg uccaaaacaa ugacggcuua uacaaaccag uuauggauuu aaagaauuug 7020
gaagccaugc ucuccuacuu caaaccagga acacuacucg agaagcugca aucuguuucu 7080
auguuggcuc aacauucugg aaaagaagaa uaugauagau ugaugcaccc cuuugcugac 7140
uacggugccg uaccgaguca cgaguaccug caggcaagau ggagggccuu guucgacuga 7200
ccuagauagc ccaacgcgcu ccggugcugc cggcgauucu gggagaacuc agucggaaca 7260
gaaaagggaa 7270
<210> 8
<211> 7270
<212> RNA
<213> 塞内卡病毒
<400> 8
cugggcccuc augcccaguc cuuccuuucc ccuuccgggg gguaaaccgg cuguguuugc 60
uagaggcaca gaggagcaac auccaaccug cuuuuguggg gaacggugcg gcuccaauuc 120
cugcgucgcc aaagguguua gcgcacccaa acggcgcauc uaccaaugcu auuggugugg 180
ucugcgaguu cuagccuacu cguuucuccc uuauccacuc acucacgcac aaaaagugug 240
cuguaacuac aagauuuagc ccucgcacga gaugugcgau aaccgcaaga uugacucaag 300
cgcggaaagc gcuguaacca caugcuguua gucccuucau ggcugcgaga uggcuaucca 360
ccucggauca cugaacugga gcucgacccu ccuuaguaag ggaaccgaga ggccuucuug 420
caacaagcuc cgacacagag uccacgugau ugcuaccacc augaguacau gguucucccc 480
ucucgaccca ggacuucuuu uugaauaucc acggcucgau ccagagggug gggcaugauc 540
ccccuagcau agcgagcuac agcgggaacu guagcuaggc cuuagcgugc cuuggauacu 600
gccugauagg gcgacggccu agucgugucg guucuauagg uagcacauac aaauaugcag 660
aacucucauu uuucuuucga uacagccucu ggcaccuuug aagacguaac cggaacaaaa 720
gucaagaucg uugaacaccc uagaucggug aacaauggug uuuacgauuc guccacucau 780
uuagagauac ugaaccuaca gggugaaauu gaaauuuuaa agucuuucaa ugaauaccaa 840
auucgcgccg ccaaacaaca acuuggacug gacaucguau acgaacuaca ggguaauguu 900
cagacaaccu caaagaauga uuuugauucc cgcgguaaua augguaacau gaccuucaau 960
uacuacgcaa acacuuacca gaauucagua gacuucucga ccuccucguc ggcgucaggc 1020
gccggacccg ggaacucccg gggcggauua gcgggucucc ucacaaauuu caguggaauc 1080
uugaacccuc uuggcuaccu caaagaucac aauaccgaag aaauggaaaa cucugcugau 1140
cgagucauaa cgcaaacggc gggcaacacu gccauaaaca cgcaaucauc acugggugug 1200
uugugugccu acguugaaga cccgaccaaa ucugacccuc cguccagcag cacagaucaa 1260
cccaccacca cuuuuacugc caucgacagg ugguacacug gacgccucaa uucuuggaca 1320
aaagcuguaa aaaccuucuc uuuucaggcc gucccgcucc cuggagccuu ccugucuaga 1380
cagggaggcc ucaacggagg ggccuucacg gcuacccuac auagacauuu cuuaaugaag 1440
ugcggguggc aggugcaggu ccaaugcaau uugacgcaau uccaccaagg ugcucuucuu 1500
guugccaugg uccccgaaac cacccuugau gucaaaccug acggcaaggc aaagagcuua 1560
caggagcuga augaagaaca guggguggaa augucugacg auuaccggac cgggaaaaac 1620
augccuuucc agucucuugg cacauacuau cggcccccua acuggacuug gggccccaau 1680
uucaucaacc ccuaucaagu aacaguuuuc ccacaccaaa uucugaacgc gagaaccucu 1740
accucgguag acauaagugu cccauacauc ggggagacuc cuacacaauc cucagagaca 1800
cagaacuccu ggacccuccu cguuauggug cuuguccccc uggacuacaa ggagggagcc 1860
acaacugacc cagaaauuac auuuucugua aggccuacaa guccuuauuu caaugggcua 1920
cguaaccguu ucacgaccgg gacggacgag gaacaggggc ccauucccac agcacccaga 1980
gaaaauucgc uuauguuucu cucaaccauc ccugacgaca cugucccugc uuacgggaau 2040
gugcguaccc cucccgucaa uuaccucccu ggugaaauaa ccgaccucuu acaacuggcc 2100
cguauaccca cucucauggc guuugggcgg gugucugaac ccgagccugc cucagacaca 2160
uaugugcccu acguugccgu uccugcccag uucgacgaca agccucucau cuccuucccg 2220
aucacccuuu cagauccugu cuaccagaac acccugguag gcgccaucag uucgaauuuc 2280
gccaacuacc ggggguguau ccaaaucacu cugacauuuu guggacccau gauggcaaga 2340
gggaaauucc uacucucgua uucuccacca aauggagcac aaccacagac ccuuucugaa 2400
gcuaugcagu gcacguacuc uauuugggau auaggcuuga acucuaguug gaccuuuguc 2460
auccccuaca ucucgcccag ugauuaccgu gaaacucggg cuauuaccaa cucaguuuau 2520
ucugcugaug guugguuuag ccugcacaag cuaacuaaaa uuacucuacc accugacugc 2580
ccacagaguc ccuguauucu cuuuuucgcc ucugcuggug aggauuacac ccuccgucuc 2640
ccuguugauu guaauccuuc cuacguguuc cacuccaccg acaacgccga gacugggguu 2700
auugaggcgg guaacacuga caccgauuuc ucuggugagc uggcggcucc uggcucuaac 2760
cacacuaaug ucaaguuccu guuugaucga ucucgauuac ugaauguaau uaagguacug 2820
gagaaggacg ccgucuuccc ccguccuuuc cccacagcaa caggugcaca gcaggacgau 2880
gguuacuuuu gccuucuaac accccgccca acagucgcuu cccgacccgc cacccguuuc 2940
ggccuguacg ucaauccguc ugacaguggc guucucgcua acacuucacu ggauuucaau 3000
uuuuacagcu uggccuguuu cacuuacuuu agaucagacc uugaagucac gguggucuca 3060
cuggagccag aucuggaauu cgcuguaggg ugguuccccu cuggcaguga guaccaggcu 3120
uccagcuuug ucuacgacca acugcaugua cccuaccacu uuacugggcg cacuccccgc 3180
gcuuucacca gcaagggugg aaagguaucu uucgugcuuc cuuggaacuc ugucucaucc 3240
gugcuucccg ugcgcugggg gggcgcuucc aagcuuucuu ccgccacgcg gggucuaccg 3300
gcucaugcug acugggggac cauuuacgcc uucauccccc guccuaacga gaagaaaagc 3360
accgcuguaa agcacguggc gguguacguu cgguacaaga acgcgcgugc cuggugcccc 3420
agcaugcucc ccuuccgcag cuacaagcag aagaugcuga ugcaaucagg cgacgucgag 3480
accaacccug gcccugcuuc ugacaaccca aucuuggagu uucuugaagc ugaaaacgau 3540
cuagucacuc uggccucucu cuggaagaug guacacucug uucaacagac cuggagaaag 3600
uaugugaaaa acgacaauuu uuggcccaau uugcucagug agcuaguggg ggaaggcucc 3660
aucgccuugg ccgccacgcu aucuaaccaa gcuucaguaa aagcucucuu aggccugcau 3720
uuucucuccc gagggcucaa uuauacagau uuuuacucuu uacugauaga gaaaugcucu 3780
aguuucuuua cuguagaacc gccuccucca ccagcugaaa aucugaugac caagcccucc 3840
gugaggucga aauuccgaaa gcuguuuaag augcaaggac ccauggacac agucaaagac 3900
uggaaccaaa uagccgccgg ccugaagaau uuccaauuug uucgugaccu ggucaaagag 3960
guggucgauu ggcuccaggc cuggauuaau aaagagaaag ccagcccugu ccuccaguac 4020
cagcuggaga ugaagaaacu cggacccgug gcuuuggcuc augaugccuu cauggccggu 4080
uccgggcccc cucuuaguga cgaccagauu gaauaucucc agaaccucaa aucucuugcc 4140
cuaacacugg ggaagacuaa uuuggcccaa agucucacca cuaugaucaa ugccaagcaa 4200
agcuccgcuc aacgagucga acccguugug gugguccuua gaggcaagcc gggauguggc 4260
aagagcuugg ccuccacguu gauugcccag gccgugucca agcgucucua cggcucacaa 4320
aguguguauu cucuuccucc ggauccagac uucuucgacg gauacaaagg acaguuugua 4380
accuugaugg acgaucuggg acaaaacccg gaugggcaag auuucuccac cuuuugucag 4440
auggugucga ccgcccaauu ucuucccaac auggcggacc uugcagaaaa ggggcguccc 4500
uucaccucca aucuuaucau ugcaacuaca aaccucccuc acuucagccc ugucaccauu 4560
gcugauccuu ccgcagucuc ucgucguauc aacuacgacc ugacucuaga aguaucugag 4620
gccuauaaga agcacacacg gcugaauuuu gaccuggcuu ucagacgcac agacgccccc 4680
cccauuuauc cuuuugcugc ccaugugccc uucguggacg uggcugugcg cuucaaaaau 4740
ggucaucaga gcuucaaucu ccuagaguug gucgacucua uuugugcaga cauucgagcc 4800
aagcaacaag gugcucgaaa uaugcagacu cugguucuac agagccccaa cgagaacgac 4860
gacacccccg ucgacgaggc guuggguaga guucucaccc ccgcugcggu cgacgaggcg 4920
cuugucgacc ucgcuccaga ugccgacccg guuggccguu uggcuauucu cgccaagcua 4980
ggucuugccc uagcugcggu caccccuggu uugauaaucu uggcaguggg acucuacagg 5040
uacuucucug gcucugauac agaccaagaa gaaacagaaa gugaggagcc ugcuaaagcg 5100
ccuaggagcg agaaugcuua ugacggcccg aagaaaaacu ccaagccccc uggagcgcuc 5160
ucccuuaugg aaaugcaaca gcccaacgug gacaugggcu uugaggcugc ggucgcuaag 5220
aaaguggucg uccccauuac cuucaugguu cccaacagac cuucuggacu uacacagucc 5280
gcucuucuug uggccggccg gaccuuccua auuaaugagc auacaugguc caaccccucc 5340
uggaccagcu ucacaauccg uggugaggug cacgcucgug augagccuuu ccaaacgguu 5400
cauuuuacuc accauggugu ucccacagau cuagugaugg uacgucucgg accgggcaac 5460
ucuuucccua acaaucuaga caaguuugga cuugaucaga ugccggcacg uaacucccgu 5520
gugguuggcg uuucggcuag uuacggcaac uucuucuucu cugggaacuu ccucggguuu 5580
guugacucca ucaccucuga ccaaggaacu uaugcgagac uuuuuaggua cagggugacg 5640
acuuacaagg gauggugcgg uucggcccug guuugugagg ccgguggugu ccggcgcauc 5700
auuggccugc auucugcugg ugccgcuggu aucggcgccg ggacuuacau cucaaaauua 5760
ggacugauca aagcccucaa acaccucggu gaaccucugg cuacaaugca agggcugaug 5820
acugagcuag agccuggagu caccgugcau guaccccgga aaucuaaauu gagaaagacg 5880
accgcacacg cgguguacaa accggaguuu gaaccugcug uguugucaaa auuugauccc 5940
agacugaaca aggauguuga ccuagaugag gcaauuuggu cuaaacacac ugccaacguc 6000
ccuuaucaac cuccuuuguu cuacacauac augucagagu acgcucaucg gguuuucucc 6060
uuuuugggaa aagacaauga cauucugacc gucaaagaag caauuuuggg aaucccugga 6120
cuagacccua uggaucccca cacagcuccg ggucugcccu acgccauuag cggccuucga 6180
cguacugauc ucgucgauuu ugcgaacggc acgguagacc cgauacuggc caugcaaauc 6240
caaaaauucu uagacgguga cuacucugau caugucuucc aaacuuuucu gaaagaugaa 6300
aucagacccu cagagaaggu ccgagcggga aaaacccgca uugucgaugu gcccucccug 6360
gcgcacugca uugugggcag aauguugcuu gggcgcuuug ccgccaaguu ucaaucccau 6420
ccuggcuuuc uccuuggcuc ugcuauuggg ucugacccug augucuucug gaccgucaua 6480
ggggcucagc ucgagggaag aaagaacacg uaugacgugg acuacagugc cuuugacucu 6540
ucacacggca cuggcuccuu cgaggcucuc aucucucacu uuuucaccgu ggacaauggu 6600
uuuagcccug cgcugggacc guaucucaga ucccuggcug ucucggugca cgcuuacggc 6660
gagcgucgca ucaagauuac cggaggccuc cccucugguu gugccgcgac cagccugcug 6720
aacacagugc ucaacaaugu gaucaucagg acugcucugg cauugaccua caaggaauuu 6780
gaauaugaca ugguugauau caucgccuac ggugacgacc uucugguugg uacggauuac 6840
gaucuggacu ucaaugaggu ggcgcggcgc gcugccaaac ugggguauaa gaugacuccu 6900
gccaacaaag guucugucuu cccuccgacu uccucucucu ccgacgcugu uuuucuaaaa 6960
cgcaaauucg uccaaaacaa ugacggcuua uacaaaccag uuauggauuu aaagaauuug 7020
gaagccaugc ucuccuacuu caaaccagga acacuacucg agaagcugca aucuguuucu 7080
auguuggcuc aacauucugg aaaagaagaa uaugauagau ugaugcaccc cuuugcugac 7140
uacggugccg uaccgaguca cgaguaccug caggcaagau ggagggccuu guucgacuga 7200
ccuagauagc ccaacgcgcu ccggugcugc cggcgauucu gggagaacuc agucggaaca 7260
gaaaagggaa 7270
<210> 9
<211> 7310
<212> RNA
<213> 塞内卡病毒
<400> 9
uuugaaaugg ggggcugggc ccugaugccc aguccuuccu uuccccuucc gggggguuaa 60
ccggcugugu uugcuagagg cacagagggg caacauccaa ccugcuuuug cggggaacgg 120
ugcggcuccg auuccugcgu cgccaaaggu guuagcgcac ccaaacggcg caccuaccaa 180
uguuauuggu guggucugcg aguucuagcc uacucguuuc ucccccgacc auucacucac 240
ccacgaaaag uguguuguaa ccauaagauu uaacccccgc acgggaugug cgauaaccgu 300
aagacuggcu caagcgcgga aagcgcugua accacaugcu guuagucccu uuauggcugc 360
aagauggcua cccaccucgg aucacugaac uggagcucga cccuccuuag uaagggaacc 420
gagaggccuu cgugcaacaa gcuccgacac agaguccacg ugacugcuac caccaugagu 480
acaugguucu ccccucucga cccaggacuu cuuuuugaau auccacggcu cgauccagag 540
gguggggcau gaccccuagc auagcgagcu acagcgggaa cuguagcuag gccuuagcgu 600
gccuuggaua cugccugaua gggcgacggc cuagucgugu cgguucuaua gguagcacau 660
acaaauaugc agaacucuca uuuuucuuuc gauacagccu cuggcaccuu ugaagaugua 720
accggaacaa aagucaagau cguugaauac cccagaucgg ugaacaaugg uguuuacgau 780
ucgucuacuc auuuggagau acugaaccua cagggugaaa uugaaauuuu aaggucuuuc 840
aaugaauacc aaauucgcgc cgccaaacaa caacucggac uggacaucgu guacgaacua 900
caggguaaug uucagacaac gucaaagaau gauuuugauu cccguggcaa uaaugguaac 960
augaccuuca auuacuacgc aaacacuuau cagaauucag uagacuucuc gaccuccucg 1020
ucggcgucag gcgccggacc cgggaacucc cggggcggau uagcgggucu ccucacaaau 1080
uucaguggaa ucuugaaccc ucuuggcuac cucaaagauc acaacaccga agaaauggaa 1140
aacucugcug aucgagucac aacgcaaacg gcgggcaaca cugccauaaa cacgcaauca 1200
ucauugggug uguugugugc cuacguugaa gacccgacca aaucugaucc uccguccagc 1260
agcacagauc aacccaccac cacuuucacu gccaucgaca ggugguacac uggacgucuc 1320
aauucuugga caaaagcugu aaaaaccuuc ucuuuucagg ccgucccgcu ucccggggcc 1380
uuucugucua ggcagggagg ccucaacgga ggggccuuca cagcuacccu acauagacac 1440
uuuuugauga agugcgggug gcaggugcag guccaaugua auuugacaca auuccaccaa 1500
ggcgcucuuc uuguugccau gguuccugaa accacccuug augucaagcc cgacgguaag 1560
gcaaagagcu uacaggagcu gaaugaagaa cagugggugg aaaugucuga cgauuaccgg 1620
accgggaaaa acaugccuuu ucagucucuu ggcacauacu aucggccccc uaacuggacu 1680
ugggguccca auuucaucaa ccccuaucaa guaacgguuu ucccacacca aauucugaac 1740
gcgagaaccu cuaccucggu agacauaaac gucccauaca ucggggagac ccccacgcaa 1800
uccucagaga cacagaacuc cuggacccuc cucguuaugg ugcucguucc ccuagacuau 1860
aaggaaggag ccacaacuga cccagaaauu acauuuucug uaaggccuac aagucccuac 1920
uucaaugggc uucgcaaccg cuacacggcc gggacggacg aagaacaggg gcccauuccu 1980
acggcaccca gagaaaauuc gcuuauguuu cucucaaccc ucccugacga cacugucccu 2040
gcuuacggga augugcguac cccuccuguc aauuaccucc cuggugaaau aaccgaccuu 2100
uugcaacugg cccgcauacc cacucucaug gcauuugagc gggugccuga acccgugccu 2160
gccucagaca cauaugugcc cuacguugcc guucccaccc aguucgauga caggccucuc 2220
aucuccuucc cgaucacccu uucagauccc gucuaucaga acacccuggu uggcgccauc 2280
aguucaaauu ucgccaauua ccgugggugu auccaaauca cucugacauu uuguggaccc 2340
augauggcga gagggaaauu ccugcucucg uauucucccc caaauggaac gcaaccacag 2400
acucuuuccg aagcuaugca gugcacauac ucuauuuggg acauaggcuu gaacucuagu 2460
uggaccuucg ucguccccua caucucgccc agugacuacc gugaaacucg agccauuacc 2520
aacucgguuu acuccgcuga ugguugguuu agccugcaca aguugaccaa aauuacucua 2580
ccaccugacu guccgcaaag ucccugcauu cucuuuuucg cuucugcugg ugaggauuac 2640
acucuccguc uccccguuga uuguaauccu uccuaugugu uccacuccac cgacaacgcc 2700
gagaccgggg uuauugaggc ggguaacacu gacaccgauu ucucugguga acuggcggcu 2760
ccuggcucua accacacuaa ugucaaguuc cuguuugauc gaucucgauu auugaaugua 2820
aucaagguac uggagaagga cgccguuuuc ccccgcccuu ucccuacaca agaaggugcg 2880
cagcaggaug augguuacuu uugucuucug accccccgcc caacagucgc uucccgaccc 2940
gccacucguu ucggccugua cgccaauccg uccggcagug guguucuugc uaacacuuca 3000
cuggacuuca auuuuuauag cuuggccugu uucacuuacu uuagaucgga ccuugagguu 3060
acgguggucu cacuagagcc ggaucuggaa uuugcuguag ggugguuucc uucuggcagu 3120
gaauaccagg cuuccagcuu ugucuacgac cagcugcaug ugcccuucca cuuuacuggg 3180
cgcacucccc gcgcuuucgc uagcaagggu gggaagguau cuuucgugcu cccuuggaac 3240
ucugucucgu cugugcuccc cgugcgcugg gggggggcuu ccaagcucuc uucugcuacg 3300
cggggucuac cggcgcaugc ugauuggggg acuauuuacg ccuuuguccc ccguccuaau 3360
gagaagaaaa gcaccgcugu aaaacacgug gccguguaca uucgguacaa gaacgcacgu 3420
gccuggugcc ccagcaugcu ucccuuucgc agcuacaagc agaagaugcu gaugcaaucu 3480
ggcgauaucg agaccaaucc ugguccugcu ucugacaacc caauuuugga guuucuugaa 3540
gcagaaaaug aucuagucac ucuggccucu cucuggaaga uggugcacuc uguucaacag 3600
accuggagaa aguaugugaa gaacgaugau uuuuggccca auuuacucag cgagcuagug 3660
ggggaaggcu cugucgccuu ggccgccacg cuauccaacc aagcuucagu aaaggcucuu 3720
uugggccugc acuuucucuc ucgggggcuc aauuacacug acuuuuacuc uuuacugaua 3780
gagaaaugcu cuaguuucuu uaccguagaa ccaccuccuc caccagcuga aaaccugaug 3840
accaagcccu cagugaaguc gaaauuccga aaacuguuua agaugcaagg acccauggac 3900
aaagucaaag acuggaacca aauagcugcc ggcuugaaga auuuucaauu uguucgugac 3960
cuagucaaag agguggucga uuggcugcag gccuggauca acaaagagaa agccagcccu 4020
guccuccagu accaguugga gaugaagaag cucgggccug uggccuuggc ucaugacgcu 4080
uucauggcug guuccgggcc cccucuuagc gacgaccaga uugaauaccu ccagaaccuc 4140
aaaucucuug cccuaacacu ggggaagacu aauuuggccc aaagucucac cacuaugauc 4200
aaugccaaac aaaguucagc ccaacgaguu gaacccguug uggugguccu uagaggcaag 4260
ccgggaugcg gcaagagcuu ggccucuacg uugauugccc aggcuguguc caagcgccuc 4320
uauggcuccc aaaguguaua uucucuuccc ccagauccag auuucuucga uggauacaaa 4380
ggacaguucg ugaccuugau ggaugauuug ggacaaaacc cggauggaca agauuucucc 4440
accuuuuguc agaugguguc gaccgcccaa uuucucccca acauggcgga ccuugcagag 4500
aaagggcguc ccuuuaccuc caaucucauc auugcaacua caaaucuccc ccacuucagu 4560
ccugucacca uugcugaucc uucugcaguc ucucgccgua ucaacuacga ucugacucua 4620
gaaguaucug aggccuacaa gaaacacaca cggcugaauu uugacuuggc uuucaggcgc 4680
acagacgccc cccccauuua uccuuuugcu gcccaugugc ccuuugugga cguagcugug 4740
cgcuucaaaa auggucacca gaauuuuaau cuccuagagu uggucgauuc cauuuguaca 4800
gacauucgag ccaagcaaca aggugcccga aacaugcaga cucugguucu acagagcccc 4860
aacgagaaug augacacccc cgucgacgag gcguugggua gaguucucuc ccccgcugcg 4920
gucgaugagg cgcuugucga ccucacucca gaggccgacc cgguuggccg uuuggcuauu 4980
cuugccaagc uaggucuugc ccuagcugcg gucaccccug gucugauaau cuuggcagug 5040
ggacucuaca gguacuucuc uggcucugau gcagaccaag aagaaacaga aagugaggga 5100
ucugucaagg cacccaggag cgaaaaugcu uaugacggcc cgaagaaaaa cucuaagccc 5160
ccuggagcac ucucucucau ggaaaugcaa cagcccaacg uggacauggg cuuugaggcu 5220
gcggucgcua agaaaguggu cguccccauu accuucaugg uucccaacag accuucuggg 5280
cuuacacagu ccgcucuucu ggugaccggc cggaccuucc uaaucaauga acauacaugg 5340
uccaaucccu ccuggaccag cuucacaauc cgcggugagg uacacacucg ugaugagccc 5400
uuccaaacgg uucauuucac ucaccacggu auucccacag aucugaugau gguacgucuc 5460
ggaccgggca auucuuuccc uaacaaucua gacaaguuug gacuugacca gaugccggca 5520
cgcaacuccc gugugguugg cguuucgucc aguuacggaa acuucuucuu cucuggaaau 5580
uuccucggau uuguugauuc caucaccucu gaacaaggaa cuuacgcaag acucuuuagg 5640
uacaggguga cgaccuacaa aggauggugc ggcucggccc uggucuguga ggccgguggc 5700
guccgacgca ucauuggccu gcauucugcu ggcgccgccg guaucggcgc cgggaccuau 5760
aucucaaaau uaggacuaau caaagcccug aaacaccucg gugaaccuuu ggccacaaug 5820
caaggacuga ugacugaauu agagccugga aucaccguac auguaccccg gaaauccaaa 5880
uugagaaaga cgaccgcaca cgcgguguac aaaccggagu uugagccugc uguguuguca 5940
aaauuugauc ccagacugaa caaggauguu gacuuggaug aaguaauuug gucuaaacac 6000
acugccaaug ucccuuacca accuccuuug uucuacacau acaugucaga guacgcucau 6060
cgagucuucu ccuucuuggg gaaagacaau gacauucuga ccgucaaaga agcaauucug 6120
ggcauccccg gacuagaccc cauggauccc cacacagcuc cgggucugcc uuacgccauc 6180
aacggccuuc gacguacuga ucucgucgau uuugugaacg guacaguaga ugcggcgcug 6240
gcuguacaaa uccagaaauu cuuagacggu gacuacucug accaugucuu ccaaacuuuu 6300
cugaaagaug agaucagacc cucagagaaa guccgagcgg gaaaaacccg cauuguugau 6360
gugcccuccc uggcgcauug cauugugggc agaauguugc uugggcgcuu ugcugccaag 6420
uuucaauccc auccuggcuu ucuccucggc ucugcuaucg ggucugaccc ugauguuuuc 6480
uggaccguca uaggggcuca acucgagggg agaaagaaca cguaugacgu ggacuacagu 6540
gccuuugacu cuucacacgg cacuggcucc uucgaggcuc ucaucucuca cuuuuucacc 6600
guggacaaug guuuuagccc ugcgcuggga ccguaucuca gaucccuggc ugucucggug 6660
cacgcuuacg gcgagcgucg caucaagauu accgguggcc uccccuccgg uugugccgcg 6720
accagccugc ugaacacagu gcucaacaau gugaucauca ggacugcucu ggcauugacu 6780
uacaaggaau uugaauauga caugguugau aucaucgccu acggugacga ccuucugguu 6840
ggcacggauu acgaucugga cuucaaugag guggcacgac gcgcugccaa guugggguau 6900
aagaugacuc cugccaacaa ggguucuguc uucccuccga cuuccucucu uuccgaugcu 6960
guuuuucuaa agcgcaaauu cguccaaaac aacgacggcu uauacaaacc aguuauggau 7020
uuaaagaauu uggaagccau gcucuccuac uucaaaccag gaacacuacu cgagaagcug 7080
caaucuguuu cuauguuggc ucaacauucu ggaaaagaag aauaugauag auugaugcac 7140
cccuucgcug acuacggugc cguaccgagu cacgaguacc ugcaggcaag auggagggcc 7200
uuguucgacu gacccagaua gcccaaggcg cuucggugcu gccggcgauu cugggagaac 7260
ucagucggaa cagaaaaggg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 7310
<210> 10
<211> 7356
<212> RNA
<213> 塞内卡病毒
<400> 10
aggggggggc ugggcccuca ugcccagucc uuccuuuccc cuuccggggg guaaaccggc 60
uguguuugcu agaggcacag aggagcaaca cccaaccugc uuuugugggg aacggugcgg 120
cuccgauucc ugcgucgcca aagguguuag cgcacccaaa cggcgcaucu accaaugcua 180
uugguguggu cugcgaguuc uagccuacuc guuucucccc uauccauuca cucacgcaca 240
aaaagugugu uguaacuaca agauuuagcc cucgcacgag augugcgaua accgcaagac 300
ugacucaagc gcggaaagcg cuguaaccac augcuguuag ucccuuuaug gcugcgagau 360
ggcuauccac cucggaucac ugaacuggag cucgacccuc cuuaguaagg gaaccgagag 420
gccuucuugc aacaagcucc gacacagagu ccacgugauu gcuaccacca ugaguacaug 480
guucuccccu cucgacccag gacuucuuuu ugaauaucca cggcucgauc cagagggugg 540
ggcaugaucc cccuagcaua gcgagcuaca gcgggaacug uagcuaggcc uuagcgugcc 600
uuggauacug ccugauaggg cgacggccua gucgugucgg uucuauaggu agcacauaua 660
aauaugcaga acucucauuu uucuuucgau acagccucug gcaccuuuga agacguaacc 720
ggaacaaaag ucaagaucgu ugaauacccc agaucgguga acaauggugu uuacgauucg 780
uccacucauu uagagauacu gaaccuacag ggugaaauug aaauuuuaag gucuuucaau 840
gaauaccaaa uucgcgccgc caaacaacaa cuuggacugg acauuguaua cgaacuacag 900
gguaauguuc agacaaccuc aaagaaugau uuugauuccc gcggcaauaa cgguaacaug 960
accuucaauu acuacgcaaa cacuuaucag aauucaguag acuucucgac cuccucgucg 1020
gcgucaggcg ccgggcccgg gaacucccgg ggcggauuag cgggucuccu cacaaauuuc 1080
aguggaaucu ugaacccucu uggcuaccuc aaagaucaca auaccgaaga aauggaaaac 1140
ucugcugauc gagucauaac gcaaacggcg ggcaacacug ccauaaacac gcaaucauca 1200
cugggugugu ugugugccua uguugaagac ccgaccaaau cugacccucc guccagcagc 1260
acagaucaac ccaccaccac uuuuacugcc aucgacaggu gguacacugg acgccucaau 1320
ucuuggacaa aagcuguaaa aaccuucucu uuucaggccg ucccgcuccc uggagccuuc 1380
cugucuagac agggaggccu caacggaggg gccuucacgg cuacccuaca cagacauuuc 1440
uuaaugaagu gcggguggca ggugcagguc caaugcaauu ugacacaauu ccaccaaggu 1500
gcucuucuug uugccauggu ccccgaaacc acccuygaug ucaagcccga cggcaaggca 1560
aagagccuac aggagcugaa ugaagagcag uggguagaaa ugucugacga uuaccggacc 1620
gggaaaaaca ugccuuuuca gucucuuggc acauacuauc ggcccccuaa cuggacuugg 1680
ggcccuaauu ucaucaaccc cuaucaagua acaguuuucc cacaccaaau ucugaacgcg 1740
agaaccucua ccucgguaga cauaaguguc ccauacaucg gggagacucc uacacaaucc 1800
ucagagacac agaacuccug gacccuccuc guuauggugc uugucccccu ggacuacaag 1860
gagggagcca caacugaccc agaaauuaca uuuucuguaa ggccuacaag uccuuacuuc 1920
aaugggcuuc guaaccguua cacgaccggg acggacgagg aacaggggcc cauucccaca 1980
gcacccagag aaaauucgcu uauguuucuc ucaaccaucc cugacgacac ugucccugcu 2040
uacgggaaug ugcguacccc ucccgucaau uaccucccug gugaaauaac cgaccucuua 2100
caacuggccc guauacccac ucucauggcg uuugggcggg ugucugaacc cgagccugcc 2160
ucagacgcau augugcccua cguugccguu cccacccagu ucgaugacaa gccucucauc 2220
uccuucccga ucacccuuuc agauccuguc uaccagaaca cccugguagg cgccaucagu 2280
ucgaauuucg ccaacuaccg gggguguauc caaaucacuc ugacauuuug uggacccaug 2340
auggcaagag ggaaauuccu acucucguau ucucccccaa auggaacgca accacagacu 2400
cuuucugaag ccaugcagug cacauacucc auuugggaua uaggcuugaa cucuaguugg 2460
accuuuguca uccccuacau cucgcccagu gacuaccgug aaacucgggc caucaccaac 2520
ucgguuuacu cugccgaugg uugguuuagc cugcacaagc ugaccaaaau cacucuaccg 2580
ccugacugcc cacagaaacc cuguauucuc uuuuucgccu cugcugguga ggauuacacc 2640
cuccgucucc ccguugauug uaauccuucc uacguguucc acuccaccga caacgccgag 2700
acugggguua uugaggcggg uaacacugac accgauuucu cuggugaacu ggcggcuccu 2760
ggcucuaacc acacuaaugu caaguuccug uuugaucgau cucgauuacu gaauguaauu 2820
aagguacugg agaaggacgc cgucuucccc cguccuuucc ccacagaaac aggugcgcag 2880
caggacgaug guuacuuuug ucuucuaaca ccccgcccaa cagucgccuc ccgacccgcc 2940
acucguuucg gccuguacgu caauccgucu gacaguggcg uucucgccaa cacuucacug 3000
gauuucaauu uuuacagcuu ggccuguuuc acuuacuuua gaucagaccu ugaagucacg 3060
guggucucac uggagccaga ucuggaauuu gcuguagggu gguuccccuc uggcagugag 3120
uaccaggcuu ccagcuuugu cuacgaccaa cugcauguac ccuaccacuu uaccgggcgc 3180
acuccccgcg cuuucaccag caaggguggg aagguaucuu ucgugcuccc uuggaacucu 3240
gucucauccg ugcuucccgu gcgcuggggg gcggcuucca agcucucuuc ugccacgcgg 3300
gguuugccgg cgcaugcuga cugggggacu auuuaugcuu ucgucccccg uccuaaugag 3360
aagaaaagca ccgcuguaaa gcacguggcc guguacguuc gguacaagaa cgcacgugcc 3420
uggugcccua gcaugcuucc cuuucgcagc uacaagcaga agaugcugau gcaaucuggc 3480
gauaucgaga ccaauccugg cccugcuucu gacaacccaa ucuuggaguu ucuugaggca 3540
gaaaacgauc uagucacucu ggccucucuc uggaagaugg uacacucugu ucagcagacc 3600
uggagaaagu acgugaagaa cgacaacuuu uggcccaauu uacucaguga gcuggugggg 3660
gaaggcucca ucgccuuggc cgccacacua uccaaccaag cuucaguaaa ggcucucuug 3720
ggccugcauu uucucucccg ggggcucaau uacacagacu uuuacuccuu acugauagag 3780
aaaugcucua guuucuucac uguagaacca ccuccuccac cagccgagaa ccugaugacc 3840
aagcccuccg ugaagucgaa auuccgaaag cuguuuaaga ugcaagggcc cauggacaaa 3900
gucaaagacu ggaaccaaau agccgccggu uugaagaauu uccaauuugu ccgugaccua 3960
gucaaagagg uggucgacug gcugcaggcc uggaucaaca aggagaaagc cagcccuguc 4020
cuccaguauc aguuagagau gaagaagcuc gggccugugg cucuggcuca ugaugcuuuc 4080
auggcugguu cugggccccc ucuuagugac gaucagauug aauaucucca gaaccuuaaa 4140
ucucuugccc uaacacuggg gaagacuaau uuggcccaaa gucucaccac uaugaucaau 4200
gccaaacaaa guuccgccca acgagucgaa cccguugugg ugguccuuag aggcaagccg 4260
ggaugcggca agagcuuggc cuccacgcug auugcccagg cuguguccaa gcgucucuac 4320
ggcucccaaa guguguauuc ucuucccccg gauccagauu ucuucgacgg auacaaagga 4380
caguuuguaa ccuugaugga ugaucuggga caaaacccgg auggacaaga uuucuccacc 4440
uuuugucaga uggugucgac cgcccaauuu cuccccaaca uggcggaccu ugcagagaag 4500
gggcgucccu ucaccuccaa ucuuaucauu gcaaccacaa accuccccca cuucagcccu 4560
gucaccauug cugauccuuc cgcagucucu cgucguauca acuacgaccu gacucuagaa 4620
guaucugagg ccuacaagaa gcauacacgg cugaauuuug accuggcuuu caggcgcaca 4680
gacgcccccc ccauuuaucc uuuugcugcc caugugcccu ucguggacgu agcugugcgc 4740
uucaaaaaug gucaccagaa cuuuaaucuc cuagaguugg ucgacuccau uugugcagac 4800
auucgagcca agcaacaagg ugcccggaac augcagacuu uggucuuaca gagcccuaau 4860
gagaaugaug acacccccgu cgacgaggcg uuggguagag uucucacccc cgcugcgguc 4920
gacgaggcgc uugucgaccu cgcuccagag gccgauccgg uuggccgcuu ggcuauucuu 4980
gccaagcuag gucuugcccu agcugcgguc accccugguu ugauaaucuu ggcaguggga 5040
cuuuacaggu acuucucugg cucugauaca gaccaagaug aaacagaaug ugaggaaucu 5100
accaaagcac cuaggagcga aaaugcuuau gacggcccga agaaaaacuc uaagcccccu 5160
ggagcacucu cucuuaugga aaugcaacag cccaacgugg acaugggcuu ugaggcugcg 5220
gucgcuaaga aaguggucgu ccccauuacc uucaugguuc ccaacagacc cucuggacuu 5280
acacaguccg cucuucuugu ggccggccgg accuuccuaa ucaaugagca cacaugguca 5340
aaucccuccu ggaccagcuu caccauccgu ggugaggugc auacucguga ugagccuuuu 5400
caaacgguuc auuuuaccca ccaugguguu cccacagauc ugaugauggu acgucucgga 5460
ccgggcaacu cuuucccuaa caaucuagac aaguuuggac uugaccagau gccggcacgc 5520
aacucccgug ugguuggcgu uucgucuagu uacggcaauu ucuucuucuc ugggaauuuc 5580
cucggguucg uugacuccau caccucugaa caaggaacuu augcaagacu uuuuagguac 5640
agggugacga cuuacaaggg cuggugcggc ucggcccugg ucugugaggc cggugguguc 5700
cggcgcauca uuggccugca uucugcuggu gccgcuggua uuggugccgg gaccuacauc 5760
ucaaaauuag gacugaucaa agcucugaaa caccucggug aaccucuggc uacaaugcaa 5820
ggacugauga cugaguuaga gccuggaauc accguacaug uaccccggaa aucuaaauug 5880
agaaagacga ccgcacacgc aguguacaaa ccggaguuug aaccugcugu guugucaaaa 5940
uuugauccca gacugaacaa ggauguugac uuagaugagg uaauuugguc uaaacacacu 6000
gccaacgucc ccuaucaacc uccuuuguuc uacacauaca ugucagagua cgcucaucga 6060
guuuucuccu ucuugggaaa agacaaugac auucugaccg ucaaagaagc aauccugggc 6120
aucccuggac uagaccccau ggauccccac acagcuccgg gucugcccua ugccauuaac 6180
ggccuucgac guacugaucu cgucgacuuu gugaacggca cgguagacgc agcgcuggcc 6240
augcaaaucc agaaauucuu agacggugac uacucugauc augucuucca aacuuuucug 6300
aaagaugaaa ucagacccuc agagaagguc cgagcgggaa aaacccgcau ugucgaugug 6360
cccucccugg cgcauugcau ugugggcaga augcugcuug ggcgcuuugc cgccaaguuu 6420
caaucccauc cuggcuuucu ccuuggcucu gcuaucggcu cugacccuga uguuuucugg 6480
accgucauag gggcucagcu cgagggaaga aagaacacgu augacgugga uuacagugcc 6540
uuugacucuu cacacggcac uggcuccuuc gaggcucuca ucucucacuu uuucaccgug 6600
gacaaugguu uuagcccugc gcugggaccg uaucucagau cccuggcugu cucggugcac 6660
gcuuacggcg agcgucgcau caagauuacc gguggccucc ccuccgguug ugccgcgacc 6720
agcuugcuga acacagugcu caacaaugug aucaucagga cugcucuggc auugacuuac 6780
aaggaauuug aguaugacau gguugauauc aucgccuacg gugacgaccu ucugguuggu 6840
acggauuacg aucuggacuu caaugaggug gcacgacgcg cugccaaacu gggguauaag 6900
augacucccg ccaacaaagg uuccgucuuc ccuccgacuu ccucucucuc cgaugcuguu 6960
uuucuaaaac gcaaauucgu ccaaaacaau gauggcuuau acaaaccagu uauggauuua 7020
aagaauuugg aagccaugcu cuccuacuuc aaaccaggaa cacuacucga gaagcugcaa 7080
ucuguuucua uguuggcuca acauucugga aaagaagaau augauagauu gaugcacccc 7140
uucgcugacu acggugccgu accgagucac gaguaccugc aggcaagaug gagggccuug 7200
uucgauugac ccagauagcc caaggcgcuu cggugcugcc ggcgauucug ggagaacuca 7260
gucggaacag aaaagggaaa aaaaaaawaa aaaaaaraaa aaaacaaaaa auaaaaacaa 7320
aaauaaacac gaccucacua cgagagcuga gacugc 7356
<210> 11
<211> 7310
<212> RNA
<213> 塞内卡病毒
<400> 11
uuugaaaugg ggggcugggc ccugaugccc aguccuuccu uuccccuucc gggggguuaa 60
ccggcugugu uugcuagagg cacagagggg caacauccaa ccugcuuuug cggggaacgg 120
ugcggcuccg auuccugcgu cgccaaaggu guuagcgcac ccaaacggcg caccuaccaa 180
uguuauuggu guggucugcg aguucuagcc uacucguuuc ucccccgacc auucacucac 240
ccacgaaaag uguguuguaa ccauaagauu uaacccccgc acgggaugug cgauaaccgu 300
aagacuggcu caagcgcgga aagcgcugua accacaugcu guuagucccu uuauggcugc 360
aagauggcua cccaccucgg aucacugaac uggagcucga cccuccuuag uaagggaacc 420
gagaggccuu cgugcaacaa gcuccgacac agaguccacg ugacugcuac caccaugagu 480
acaugguucu ccccucucga cccaggacuu cuuuuugaau auccacggcu cgauccagag 540
gguggggcau gaccccuagc auagcgagcu acagcgggaa cuguagcuag gccuuagcgu 600
gccuuggaua cugccugaua gggcgacggc cuagucgugu cgguucuaua gguagcacau 660
acaaauaugc agaacucuca uuuuucuuuc gauacagccu cuggcaccuu ugaagaugua 720
accggaacaa aagucaagau cguugaauac cccagaucgg ugaacaaugg uguuuacgau 780
ucgucuacuc auuuggagau acugaaccua cagggugaaa uugaaauuuu aaggucuuuc 840
aaugaauacc aaauucgcgc cgccaaacaa caacucggac uggacaucgu guacgaacua 900
caggguaaug uucagacaac gucaaagaau gauuuugauu cccguggcaa uaaugguaac 960
augaccuuca auuacuacgc aaacacuuau cagaauucag uagacuucuc gaccuccucg 1020
ucggcgucag gcgccggacc cgggaacucc cggggcggau uagcgggucu ccucacaaau 1080
uucaguggaa ucuugaaccc ucuuggcuac cucaaagauc acaacaccga agaaauggaa 1140
aacucugcug aucgagucac aacgcaaacg gcgggcaaca cugccauaaa cacgcaauca 1200
ucauugggug uguugugugc cuacguugaa gacccgacca aaucugaucc uccguccagc 1260
agcacagauc aacccaccac cacuuucacu gccaucgaca ggugguacac uggacgucuc 1320
aauucuugga caaaagcugu aaaaaccuuc ucuuuucagg ccgucccgcu ucccggggcc 1380
uuucugucua ggcagggagg ccucaacgga ggggccuuca cagcuacccu acauagacac 1440
uuuuugauga agugcgggug gcaggugcag guccaaugua auuugacaca auuccaccaa 1500
ggcgcucuuc uuguugccau gguuccugaa accacccuug augucaagcc cgacgguaag 1560
gcaaagagcu uacaggagcu gaaugaagaa cagugggugg aaaugucuga cgauuaccgg 1620
accgggaaaa acaugccuuu ucagucucuu ggcacauacu aucggccccc uaacuggacu 1680
ugggguccca auuucaucaa ccccuaucaa guaacgguuu ucccacacca aauucugaac 1740
gcgagaaccu cuaccucggu agacauaaac gucccauaca ucggggagac ccccacgcaa 1800
uccucagaga cacagaacuc cuggacccuc cucguuaugg ugcucguucc ccuagacuau 1860
aaggaaggag ccacaacuga cccagaaauu acauuuucug uaaggccuac aagucccuac 1920
uucaaugggc uucgcaaccg cuacacggcc gggacggacg aagaacaggg gcccauuccu 1980
acggcaccca gagaaaauuc gcuuauguuu cucucaaccc ucccugacga cacugucccu 2040
gcuuacggga augugcguac cccuccuguc aauuaccucc cuggugaaau aaccgaccuu 2100
uugcaacugg cccgcauacc cacucucaug gcauuugagc gggugccuga acccgugccu 2160
gccucagaca cauaugugcc cuacguugcc guucccaccc aguucgauga caggccucuc 2220
aucuccuucc cgaucacccu uucagauccc gucuaucaga acacccuggu uggcgccauc 2280
aguucaaauu ucgccaauua ccgugggugu auccaaauca cucugacauu uuguggaccc 2340
augauggcga gagggaaauu ccugcucucg uauucucccc caaauggaac gcaaccacag 2400
acucuuuccg aagcuaugca gugcacauac ucuauuuggg acauaggcuu gaacucuagu 2460
uggaccuucg ucguccccua caucucgccc agugacuacc gugaaacucg agccauuacc 2520
aacucgguuu acuccgcuga ugguugguuu agccugcaca aguugaccaa aauuacucua 2580
ccaccugacu guccgcaaag ucccugcauu cucuuuuucg cuucugcugg ugaggauuac 2640
acucuccguc uccccguuga uuguaauccu uccuaugugu uccacuccac cgacaacgcc 2700
gagaccgggg uuauugaggc ggguaacacu gacaccgauu ucucugguga acuggcggcu 2760
ccuggcucua accacacuaa ugucaaguuc cuguuugauc gaucucgauu auugaaugua 2820
aucaagguac uggagaagga cgccguuuuc ccccgcccuu ucccuacaca agaaggugcg 2880
cagcaggaug augguuacuu uugucuucug accccccgcc caacagucgc uucccgaccc 2940
gccacucguu ucggccugua cgccaauccg uccggcagug guguucuugc uaacacuuca 3000
cuggacuuca auuuuuauag cuuggccugu uucacuuacu uuagaucgga ccuugagguu 3060
acgguggucu cacuagagcc ggaucuggaa uuugcuguag ggugguuucc uucuggcagu 3120
gaauaccagg cuuccagcuu ugucuacgac cagcugcaug ugcccuucca cuuuacuggg 3180
cgcacucccc gcgcuuucgc uagcaagggu gggaagguau cuuucgugcu cccuuggaac 3240
ucugucucgu cugugcuccc cgugcgcugg gggggggcuu ccaagcucuc uucugcuacg 3300
cggggucuac cggcgcaugc ugauuggggg acuauuuacg ccuuuguccc ccguccuaau 3360
gagaagaaaa gcaccgcugu aaaacacgug gccguguaca uucgguacaa gaacgcacgu 3420
gccuggugcc ccagcaugcu ucccuuucgc agcuacaagc agaagaugcu gaugcaaucu 3480
ggcgauaucg agaccaaucc ugguccugcu ucugacaacc caauuuugga guuucuugaa 3540
gcagaaaaug aucuagucac ucuggccucu cucuggaaga uggugcacuc uguucaacag 3600
accuggagaa aguaugugaa gaacgaugau uuuuggccca auuuacucag cgagcuagug 3660
ggggaaggcu cugucgccuu ggccgccacg cuauccaacc aagcuucagu aaaggcucuu 3720
uugggccugc acuuucucuc ucgggggcuc aauuacacug acuuuuacuc uuuacugaua 3780
gagaaaugcu cuaguuucuu uaccguagaa ccaccuccuc caccagcuga aaaccugaug 3840
accaagcccu cagugaaguc gaaauuccga aaacuguuua agaugcaagg acccauggac 3900
aaagucaaag acuggaacca aauagcugcc ggcuugaaga auuuucaauu uguucgugac 3960
cuagucaaag agguggucga uuggcugcag gccuggauca acaaagagaa agccagcccu 4020
guccuccagu accaguugga gaugaagaag cucgggccug uggccuuggc ucaugacgcu 4080
uucauggcug guuccgggcc cccucuuagc gacgaccaga uugaauaccu ccagaaccuc 4140
aaaucucuug cccuaacacu ggggaagacu aauuuggccc aaagucucac cacuaugauc 4200
aaugccaaac aaaguucagc ccaacgaguu gaacccguug uggugguccu uagaggcaag 4260
ccgggaugcg gcaagagcuu ggccucuacg uugauugccc aggcuguguc caagcgccuc 4320
uauggcuccc aaaguguaua uucucuuccc ccagauccag auuucuucga uggauacaaa 4380
ggacaguucg ugaccuugau ggaugauuug ggacaaaacc cggauggaca agauuucucc 4440
accuuuuguc agaugguguc gaccgcccaa uuucucccca acauggcgga ccuugcagag 4500
aaagggcguc ccuuuaccuc caaucucauc auugcaacua caaaucuccc ccacuucagu 4560
ccugucacca uugcugaucc uucugcaguc ucucgccgua ucaacuacga ucugacucua 4620
gaaguaucug aggccuacaa gaaacacaca cggcugaauu uugacuuggc uuucaggcgc 4680
acagacgccc cccccauuua uccuuuugcu gcccaugugc ccuuugugga cguagcugug 4740
cgcuucaaaa auggucacca gaauuuuaau cuccuagagu uggucgauuc cauuuguaca 4800
gacauucgag ccaagcaaca aggugcccga aacaugcaga cucugguucu acagagcccc 4860
aacgagaaug augacacccc cgucgacgag gcguugggua gaguucucuc ccccgcugcg 4920
gucgaugagg cgcuugucga ccucacucca gaggccgacc cgguuggccg uuuggcuauu 4980
cuugccaagc uaggucuugc ccuagcugcg gucaccccug gucugauaau cuuggcagug 5040
ggacucuaca gguacuucuc uggcucugau gcagaccaag aagaaacaga aagugaggga 5100
ucugucaagg cacccaggag cgaaaaugcu uaugacggcc cgaagaaaaa cucuaagccc 5160
ccuggagcac ucucucucau ggaaaugcaa cagcccaacg uggacauggg cuuugaggcu 5220
gcggucgcua agaaaguggu cguccccauu accuucaugg uucccaacag accuucuggg 5280
cuuacacagu ccgcucuucu ggugaccggc cggaccuucc uaaucaauga acauacaugg 5340
uccaaucccu ccuggaccag cuucacaauc cgcggugagg uacacacucg ugaugagccc 5400
uuccaaacgg uucauuucac ucaccacggu auucccacag aucugaugau gguacgucuc 5460
ggaccgggca auucuuuccc uaacaaucua gacaaguuug gacuugacca gaugccggca 5520
cgcaacuccc gugugguugg cguuucgucc aguuacggaa acuucuucuu cucuggaaau 5580
uuccucggau uuguugauuc caucaccucu gaacaaggaa cuuacgcaag acucuuuagg 5640
uacaggguga cgaccuacaa aggauggugc ggcucggccc uggucuguga ggccgguggc 5700
guccgacgca ucauuggccu gcauucugcu ggcgccgccg guaucggcgc cgggaccuau 5760
aucucaaaau uaggacuaau caaagcccug aaacaccucg gugaaccuuu ggccacaaug 5820
caaggacuga ugacugaauu agagccugga aucaccguac auguaccccg gaaauccaaa 5880
uugagaaaga cgaccgcaca cgcgguguac aaaccggagu uugagccugc uguguuguca 5940
aaauuugauc ccagacugaa caaggauguu gacuuggaug aaguaauuug gucuaaacac 6000
acugccaaug ucccuuacca accuccuuug uucuacacau acaugucaga guacgcucau 6060
cgagucuucu ccuucuuggg gaaagacaau gacauucuga ccgucaaaga agcaauucug 6120
ggcauccccg gacuagaccc cauggauccc cacacagcuc cgggucugcc uuacgccauc 6180
aacggccuuc gacguacuga ucucgucgau uuugugaacg guacaguaga ugcggcgcug 6240
gcuguacaaa uccagaaauu cuuagacggu gacuacucug accaugucuu ccaaacuuuu 6300
cugaaagaug agaucagacc cucagagaaa guccgagcgg gaaaaacccg cauuguugau 6360
gugcccuccc uggcgcauug cauugugggc agaauguugc uugggcgcuu ugcugccaag 6420
uuucaauccc auccuggcuu ucuccucggc ucugcuaucg ggucugaccc ugauguuuuc 6480
uggaccguca uaggggcuca acucgagggg agaaagaaca cguaugacgu ggacuacagu 6540
gccuuugacu cuucacacgg cacuggcucc uucgaggcuc ucaucucuca cuuuuucacc 6600
guggacaaug guuuuagccc ugcgcuggga ccguaucuca gaucccuggc ugucucggug 6660
cacgcuuacg gcgagcgucg caucaagauu accgguggcc uccccuccgg uugugccgcg 6720
accagccugc ugaacacagu gcucaacaau gugaucauca ggacugcucu ggcauugacu 6780
uacaaggaau uugaauauga caugguugau aucaucgccu acggugacga ccuucugguu 6840
ggcacggauu acgaucugga cuucaaugag guggcacgac gcgcugccaa guugggguau 6900
aagaugacuc cugccaacaa ggguucuguc uucccuccga cuuccucucu uuccgaugcu 6960
guuuuucuaa agcgcaaauu cguccaaaac aacgacggcu uauacaaacc aguuauggau 7020
uuaaagaauu uggaagccau gcucuccuac uucaaaccag gaacacuacu cgagaagcug 7080
caaucuguuu cuauguuggc ucaacauucu ggaaaagaag aauaugauag auugaugcac 7140
cccuucgcug acuacggugc cguaccgagu cacgaguacc ugcaggcaag auggagggcc 7200
uuguucgacu gacccagaua gcccaaggcg cuucggugcu gccggcgauu cugggagaac 7260
ucagucggaa cagaaaaggg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 7310
<210> 12
<211> 7310
<212> RNA
<213> 塞内卡病毒
<400> 12
uuugaaaugg ggggcugggc ccugaugccc aguccuuccu uuccccuucc gggggguuaa 60
ccggcugugu uugcuagagg cacagagggg caacauccaa ccugcuuuug cggggaacgg 120
ugcggcuccg auuccugcgu cgccaaaggu guuagcgcac ccaaacggcg caccuaccaa 180
uguuauuggu guggucugcg aguucuagcc uacucguuuc ucccccgacc auucacucac 240
ccacgaaaag uguguuguaa ccauaagauu uaacccccgc acgggaugug cgauaaccgu 300
aagacuggcu caagcgcgga aagcgcugua accacaugcu guuagucccu uuauggcugc 360
aagauggcua cccaccucgg aucacugaac uggagcucga cccuccuuag uaagggaacc 420
gagaggccuu cgugcaacaa gcuccgacac agaguccacg ugacugcuac caccaugagu 480
acaugguucu ccccucucga cccaggacuu cuuuuugaau auccacggcu cgauccagag 540
gguggggcau gaccccuagc auagcgagcu acagcgggaa cuguagcuag gccuuagcgu 600
gccuuggaua cugccugaua gggcgacggc cuagucgugu cgguucuaua gguagcacau 660
acaaauaugc agaacucuca uuuuucuuuc gauacagccu cuggcaccuu ugaagaugua 720
accggaacaa aagucaagau cguugaauac cccagaucgg ugaacaaugg uguuuacgau 780
ucgucuacuc auuuggagau acugaaccua cagggugaaa uugaaauuuu aaggucuuuc 840
aaugaauacc aaauucgcgc cgccaaacaa caacucggac uggacaucgu guacgaacua 900
caggguaaug uucagacaac gucaaagaau gauuuugauu cccguggcaa uaaugguaac 960
augaccuuca auuacuacgc aaacacuuau cagaauucag uagacuucuc gaccuccucg 1020
ucggcgucag gcgccggacc cgggaacucc cggggcggau uagcgggucu ccucacaaau 1080
uucaguggaa ucuugaaccc ucuuggcuac cucaaagauc acaacaccga agaaauggaa 1140
aacucugcug aucgagucac aacgcaaacg gcgggcaaca cugccauaaa cacgcaauca 1200
ucauugggug uguugugugc cuacguugaa gacccgacca aaucugaucc uccguccagc 1260
agcacagauc aacccaccac cacuuucacu gccaucgaca ggugguacac uggacgucuc 1320
aauucuugga caaaagcugu aaaaaccuuc ucuuuucagg ccgucccgcu ucccggggcc 1380
uuucugucua ggcagggagg ccucaacgga ggggccuuca cagcuacccu acauagacac 1440
uuuuugauga agugcgggug gcaggugcag guccaaugua auuugacaca auuccaccaa 1500
ggcgcucuuc uuguugccau gguuccugaa accacccuug augucaagcc cgacgguaag 1560
gcaaagagcu uacaggagcu gaaugaagaa cagugggugg aaaugucuga cgauuaccgg 1620
accgggaaaa acaugccuuu ucagucucuu ggcacauacu aucggccccc uaacuggacu 1680
ugggguccca auuucaucaa ccccuaucaa guaacgguuu ucccacacca aauucugaac 1740
gcgagaaccu cuaccucggu agacauaaac gucccauaca ucggggagac ccccacgcaa 1800
uccucagaga cacagaacuc cuggacccuc cucguuaugg ugcucguucc ccuagacuau 1860
aaggaaggag ccacaacuga cccagaaauu acauuuucug uaaggccuac aagucccuac 1920
uucaaugggc uucgcaaccg cuacacggcc gggacggacg aagaacaggg gcccauuccu 1980
acggcaccca gagaaaauuc gcuuauguuu cucucaaccc ucccugacga cacugucccu 2040
gcuuacggga augugcguac cccuccuguc aauuaccucc cuggugaaau aaccgaccuu 2100
uugcaacugg cccgcauacc cacucucaug gcauuugagc gggugccuga acccgugccu 2160
gccucagaca cauaugugcc cuacguugcc guucccaccc aguucgauga caggccucuc 2220
aucuccuucc cgaucacccu uucagauccc gucuaucaga acacccuggu uggcgccauc 2280
aguucaaauu ucgccaauua ccgugggugu auccaaauca cucugacauu uuguggaccc 2340
augauggcga gagggaaauu ccugcucucg uauucucccc caaauggaac gcaaccacag 2400
acucuuuccg aagcuaugca gugcacauac ucuauuuggg acauaggcuu gaacucuagu 2460
uggaccuucg ucguccccua caucucgccc agugacuacc gugaaacucg agccauuacc 2520
aacucgguuu acuccgcuga ugguugguuu agccugcaca aguugaccaa aauuacucua 2580
ccaccugacu guccgcaaag ucccugcauu cucuuuuucg cuucugcugg ugaggauuac 2640
acucuccguc uccccguuga uuguaauccu uccuaugugu uccacuccac cgacaacgcc 2700
gagaccgggg uuauugaggc ggguaacacu gacaccgauu ucucugguga acuggcggcu 2760
ccuggcucua accacacuaa ugucaaguuc cuguuugauc gaucucgauu auugaaugua 2820
aucaagguac uggagaagga cgccguuuuc ccccgcccuu ucccuacaca agaaggugcg 2880
cagcaggaug augguuacuu uugucuucug accccccgcc caacagucgc uucccgaccc 2940
gccacucguu ucggccugua cgccaauccg uccggcagug guguucuugc uaacacuuca 3000
cuggacuuca auuuuuauag cuuggccugu uucacuuacu uuagaucgga ccuugagguu 3060
acgguggucu cacuagagcc ggaucuggaa uuugcuguag ggugguuucc uucuggcagu 3120
gaauaccagg cuuccagcuu ugucuacgac cagcugcaug ugcccuucca cuuuacuggg 3180
cgcacucccc gcgcuuucgc uagcaagggu gggaagguau cuuucgugcu cccuuggaac 3240
ucugucucgu cugugcuccc cgugcgcugg gggggggcuu ccaagcucuc uucugcuacg 3300
cggggucuac cggcgcaugc ugauuggggg acuauuuacg ccuuuguccc ccguccuaau 3360
gagaagaaaa gcaccgcugu aaaacacgug gccguguaca uucgguacaa gaacgcacgu 3420
gccuggugcc ccagcaugcu ucccuuucgc agcuacaagc agaagaugcu gaugcaaucu 3480
ggcgauaucg agaccaaucc ugguccugcu ucugacaacc caauuuugga guuucuugaa 3540
gcagaaaaug aucuagucac ucuggccucu cucuggaaga uggugcacuc uguucaacag 3600
accuggagaa aguaugugaa gaacgaugau uuuuggccca auuuacucag cgagcuagug 3660
ggggaaggcu cugucgccuu ggccgccacg cuauccaacc aagcuucagu aaaggcucuu 3720
uugggccugc acuuucucuc ucgggggcuc aauuacacug acuuuuacuc uuuacugaua 3780
gagaaaugcu cuaguuucuu uaccguagaa ccaccuccuc caccagcuga aaaccugaug 3840
accaagcccu cagugaaguc gaaauuccga aaacuguuua agaugcaagg acccauggac 3900
aaagucaaag acuggaacca aauagcugcc ggcuugaaga auuuucaauu uguucgugac 3960
cuagucaaag agguggucga uuggcugcag gccuggauca acaaagagaa agccagcccu 4020
guccuccagu accaguugga gaugaagaag cucgggccug uggccuuggc ucaugacgcu 4080
uucauggcug guuccgggcc cccucuuagc gacgaccaga uugaauaccu ccagaaccuc 4140
aaaucucuug cccuaacacu ggggaagacu aauuuggccc aaagucucac cacuaugauc 4200
aaugccaaac aaaguucagc ccaacgaguu gaacccguug uggugguccu uagaggcaag 4260
ccgggaugcg gcaagagcuu ggccucuacg uugauugccc aggcuguguc caagcgccuc 4320
uauggcuccc aaaguguaua uucucuuccc ccagauccag auuucuucga uggauacaaa 4380
ggacaguucg ugaccuugau ggaugauuug ggacaaaacc cggauggaca agauuucucc 4440
accuuuuguc agaugguguc gaccgcccaa uuucucccca acauggcgga ccuugcagag 4500
aaagggcguc ccuuuaccuc caaucucauc auugcaacua caaaucuccc ccacuucagu 4560
ccugucacca uugcugaucc uucugcaguc ucucgccgua ucaacuacga ucugacucua 4620
gaaguaucug aggccuacaa gaaacacaca cggcugaauu uugacuuggc uuucaggcgc 4680
acagacgccc cccccauuua uccuuuugcu gcccaugugc ccuuugugga cguagcugug 4740
cgcuucaaaa auggucacca gaauuuuaau cuccuagagu uggucgauuc cauuuguaca 4800
gacauucgag ccaagcaaca aggugcccga aacaugcaga cucugguucu acagagcccc 4860
aacgagaaug augacacccc cgucgacgag gcguugggua gaguucucuc ccccgcugcg 4920
gucgaugagg cgcuugucga ccucacucca gaggccgacc cgguuggccg uuuggcuauu 4980
cuugccaagc uaggucuugc ccuagcugcg gucaccccug gucugauaau cuuggcagug 5040
ggacucuaca gguacuucuc uggcucugau gcagaccaag aagaaacaga aagugaggga 5100
ucugucaagg cacccaggag cgaaaaugcu uaugacggcc cgaagaaaaa cucuaagccc 5160
ccuggagcac ucucucucau ggaaaugcaa cagcccaacg uggacauggg cuuugaggcu 5220
gcggucgcua agaaaguggu cguccccauu accuucaugg uucccaacag accuucuggg 5280
cuuacacagu ccgcucuucu ggugaccggc cggaccuucc uaaucaauga acauacaugg 5340
uccaaucccu ccuggaccag cuucacaauc cgcggugagg uacacacucg ugaugagccc 5400
uuccaaacgg uucauuucac ucaccacggu auucccacag aucugaugau gguacgucuc 5460
ggaccgggca auucuuuccc uaacaaucua gacaaguuug gacuugacca gaugccggca 5520
cgcaacuccc gugugguugg cguuucgucc aguuacggaa acuucuucuu cucuggaaau 5580
uuccucggau uuguugauuc caucaccucu gaacaaggaa cuuacgcaag acucuuuagg 5640
uacaggguga cgaccuacaa aggauggugc ggcucggccc uggucuguga ggccgguggc 5700
guccgacgca ucauuggccu gcauucugcu ggcgccgccg guaucggcgc cgggaccuau 5760
aucucaaaau uaggacuaau caaagcccug aaacaccucg gugaaccuuu ggccacaaug 5820
caaggacuga ugacugaauu agagccugga aucaccguac auguaccccg gaaauccaaa 5880
uugagaaaga cgaccgcaca cgcgguguac aaaccggagu uugagccugc uguguuguca 5940
aaauuugauc ccagacugaa caaggauguu gacuuggaug aaguaauuug gucuaaacac 6000
acugccaaug ucccuuacca accuccuuug uucuacacau acaugucaga guacgcucau 6060
cgagucuucu ccuucuuggg gaaagacaau gacauucuga ccgucaaaga agcaauucug 6120
ggcauccccg gacuagaccc cauggauccc cacacagcuc cgggucugcc uuacgccauc 6180
aacggccuuc gacguacuga ucucgucgau uuugugaacg guacaguaga ugcggcgcug 6240
gcuguacaaa uccagaaauu cuuagacggu gacuacucug accaugucuu ccaaacuuuu 6300
cugaaagaug agaucagacc cucagagaaa guccgagcgg gaaaaacccg cauuguugau 6360
gugcccuccc uggcgcauug cauugugggc agaauguugc uugggcgcuu ugcugccaag 6420
uuucaauccc auccuggcuu ucuccucggc ucugcuaucg ggucugaccc ugauguuuuc 6480
uggaccguca uaggggcuca acucgagggg agaaagaaca cguaugacgu ggacuacagu 6540
gccuuugacu cuucacacgg cacuggcucc uucgaggcuc ucaucucuca cuuuuucacc 6600
guggacaaug guuuuagccc ugcgcuggga ccguaucuca gaucccuggc ugucucggug 6660
cacgcuuacg gcgagcgucg caucaagauu accgguggcc uccccuccgg uugugccgcg 6720
accagccugc ugaacacagu gcucaacaau gugaucauca ggacugcucu ggcauugacu 6780
uacaaggaau uugaauauga caugguugau aucaucgccu acggugacga ccuucugguu 6840
ggcacggauu acgaucugga cuucaaugag guggcacgac gcgcugccaa guugggguau 6900
aagaugacuc cugccaacaa ggguucuguc uucccuccga cuuccucucu uuccgaugcu 6960
guuuuucuaa agcgcaaauu cguccaaaac aacgacggcu uauacaaacc aguuauggau 7020
uuaaagaauu uggaagccau gcucuccuac uucaaaccag gaacacuacu cgagaagcug 7080
caaucuguuu cuauguuggc ucaacauucu ggaaaagaag aauaugauag auugaugcac 7140
cccuucgcug acuacggugc cguaccgagu cacgaguacc ugcaggcaag auggagggcc 7200
uuguucgacu gacccagaua gcccaaggcg cuucggugcu gccggcgauu cugggagaac 7260
ucagucggaa cagaaaaggg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 7310
<210> 13
<211> 7310
<212> RNA
<213> 塞内卡病毒
<400> 13
uuugaaaugg ggggcugggc ccugaugccc aguccuuccu uuccccuucc gggggguuaa 60
ccggcugugu uugcuagagg cacagagggg caacauccaa ccugcuuuug cggggaacgg 120
ugcggcuccg auuccugcgu cgccaaaggu guuagcgcac ccaaacggcg caccuaccaa 180
uguuauuggu guggucugcg aguucuagcc uacucguuuc ucccccgacc auucacucac 240
ccacgaaaag uguguuguaa ccauaagauu uaacccccgc acgggaugug cgauaaccgu 300
aagacuggcu caagcgcgga aagcgcugua accacaugcu guuagucccu uuauggcugc 360
aagauggcua cccaccucgg aucacugaac uggagcucga cccuccuuag uaagggaacc 420
gagaggccuu cgugcaacaa gcuccgacac agaguccacg ugacugcuac caccaugagu 480
acaugguucu ccccucucga cccaggacuu cuuuuugaau auccacggcu cgauccagag 540
gguggggcau gaccccuagc auagcgagcu acagcgggaa cuguagcuag gccuuagcgu 600
gccuuggaua cugccugaua gggcgacggc cuagucgugu cgguucuaua gguagcacau 660
acaaauaugc agaacucuca uuuuucuuuc gauacagccu cuggcaccuu ugaagaugua 720
accggaacaa aagucaagau cguugaauac cccagaucgg ugaacaaugg uguuuacgau 780
ucgucuacuc auuuggagau acugaaccua cagggugaaa uugaaauuuu aaggucuuuc 840
aaugaauacc aaauucgcgc cgccaaacaa caacucggac uggacaucgu guacgaacua 900
caggguaaug uucagacaac gucaaagaau gauuuugauu cccguggcaa uaaugguaac 960
augaccuuca auuacuacgc aaacacuuau cagaauucag uagacuucuc gaccuccucg 1020
ucggcgucag gcgccggacc cgggaacucc cggggcggau uagcgggucu ccucacaaau 1080
uucaguggaa ucuugaaccc ucuuggcuac cucaaagauc acaacaccga agaaauggaa 1140
aacucugcug aucgagucac aacgcaaacg gcgggcaaca cugccauaaa cacgcaauca 1200
ucauugggug uguugugugc cuacguugaa gacccgacca aaucugaucc uccguccagc 1260
agcacagauc aacccaccac cacuuucacu gccaucgaca ggugguacac uggacgucuc 1320
aauucuugga caaaagcugu aaaaaccuuc ucuuuucagg ccgucccgcu ucccggggcc 1380
uuucugucua ggcagggagg ccucaacgga ggggccuuca cagcuacccu acauagacac 1440
uuuuugauga agugcgggug gcaggugcag guccaaugua auuugacaca auuccaccaa 1500
ggcgcucuuc uuguugccau gguuccugaa accacccuug augucaagcc cgacgguaag 1560
gcaaagagcu uacaggagcu gaaugaagaa cagugggugg aaaugucuga cgauuaccgg 1620
accgggaaaa acaugccuuu ucagucucuu ggcacauacu aucggccccc uaacuggacu 1680
ugggguccca auuucaucaa ccccuaucaa guaacgguuu ucccacacca aauucugaac 1740
gcgagaaccu cuaccucggu agacauaaac gucccauaca ucggggagac ccccacgcaa 1800
uccucagaga cacagaacuc cuggacccuc cucguuaugg ugcucguucc ccuagacuau 1860
aaggaaggag ccacaacuga cccagaaauu acauuuucug uaaggccuac aagucccuac 1920
uucaaugggc uucgcaaccg cuacacggcc gggacggacg aagaacaggg gcccauuccu 1980
acggcaccca gagaaaauuc gcuuauguuu cucucaaccc ucccugacga cacugucccu 2040
gcuuacggga augugcguac cccuccuguc aauuaccucc cuggugaaau aaccgaccuu 2100
uugcaacugg cccgcauacc cacucucaug gcauuugagc gggugccuga acccgugccu 2160
gccucagaca cauaugugcc cuacguugcc guucccaccc aguucgauga caggccucuc 2220
aucuccuucc cgaucacccu uucagauccc gucuaucaga acacccuggu uggcgccauc 2280
aguucaaauu ucgccaauua ccgugggugu auccaaauca cucugacauu uuguggaccc 2340
augauggcga gagggaaauu ccugcucucg uauucucccc caaauggaac gcaaccacag 2400
acucuuuccg aagcuaugca gugcacauac ucuauuuggg acauaggcuu gaacucuagu 2460
uggaccuucg ucguccccua caucucgccc agugacuacc gugaaacucg agccauuacc 2520
aacucgguuu acuccgcuga ugguugguuu agccugcaca aguugaccaa aauuacucua 2580
ccaccugacu guccgcaaag ucccugcauu cucuuuuucg cuucugcugg ugaggauuac 2640
acucuccguc uccccguuga uuguaauccu uccuaugugu uccacuccac cgacaacgcc 2700
gagaccgggg uuauugaggc ggguaacacu gacaccgauu ucucugguga acuggcggcu 2760
ccuggcucua accacacuaa ugucaaguuc cuguuugauc gaucucgauu auugaaugua 2820
aucaagguac uggagaagga cgccguuuuc ccccgcccuu ucccuacaca agaaggugcg 2880
cagcaggaug augguuacuu uugucuucug accccccgcc caacagucgc uucccgaccc 2940
gccacucguu ucggccugua cgccaauccg uccggcagug guguucuugc uaacacuuca 3000
cuggacuuca auuuuuauag cuuggccugu uucacuuacu uuagaucgga ccuugagguu 3060
acgguggucu cacuagagcc ggaucuggaa uuugcuguag ggugguuucc uucuggcagu 3120
gaauaccagg cuuccagcuu ugucuacgac cagcugcaug ugcccuucca cuuuacuggg 3180
cgcacucccc gcgcuuucgc uagcaagggu gggaagguau cuuucgugcu cccuuggaac 3240
ucugucucgu cugugcuccc cgugcgcugg gggggggcuu ccaagcucuc uucugcuacg 3300
cggggucuac cggcgcaugc ugauuggggg acuauuuacg ccuuuguccc ccguccuaau 3360
gagaagaaaa gcaccgcugu aaaacacgug gccguguaca uucgguacaa gaacgcacgu 3420
gccuggugcc ccagcaugcu ucccuuucgc agcuacaagc agaagaugcu gaugcaaucu 3480
ggcgauaucg agaccaaucc ugguccugcu ucugacaacc caauuuugga guuucuugaa 3540
gcagaaaaug aucuagucac ucuggccucu cucuggaaga uggugcacuc uguucaacag 3600
accuggagaa aguaugugaa gaacgaugau uuuuggccca auuuacucag cgagcuagug 3660
ggggaaggcu cugucgccuu ggccgccacg cuauccaacc aagcuucagu aaaggcucuu 3720
uugggccugc acuuucucuc ucgggggcuc aauuacacug acuuuuacuc uuuacugaua 3780
gagaaaugcu cuaguuucuu uaccguagaa ccaccuccuc caccagcuga aaaccugaug 3840
accaagcccu cagugaaguc gaaauuccga aaacuguuua agaugcaagg acccauggac 3900
aaagucaaag acuggaacca aauagcugcc ggcuugaaga auuuucaauu uguucgugac 3960
cuagucaaag agguggucga uuggcugcag gccuggauca acaaagagaa agccagcccu 4020
guccuccagu accaguugga gaugaagaag cucgggccug uggccuuggc ucaugacgcu 4080
uucauggcug guuccgggcc cccucuuagc gacgaccaga uugaauaccu ccagaaccuc 4140
aaaucucuug cccuaacacu ggggaagacu aauuuggccc aaagucucac cacuaugauc 4200
aaugccaaac aaaguucagc ccaacgaguu gaacccguug uggugguccu uagaggcaag 4260
ccgggaugcg gcaagagcuu ggccucuacg uugauugccc aggcuguguc caagcgccuc 4320
uauggcuccc aaaguguaua uucucuuccc ccagauccag auuucuucga uggauacaaa 4380
ggacaguucg ugaccuugau ggaugauuug ggacaaaacc cggauggaca agauuucucc 4440
accuuuuguc agaugguguc gaccgcccaa uuucucccca acauggcgga ccuugcagag 4500
aaagggcguc ccuuuaccuc caaucucauc auugcaacua caaaucuccc ccacuucagu 4560
ccugucacca uugcugaucc uucugcaguc ucucgccgua ucaacuacga ucugacucua 4620
gaaguaucug aggccuacaa gaaacacaca cggcugaauu uugacuuggc uuucaggcgc 4680
acagacgccc cccccauuua uccuuuugcu gcccaugugc ccuuugugga cguagcugug 4740
cgcuucaaaa auggucacca gaauuuuaau cuccuagagu uggucgauuc cauuuguaca 4800
gacauucgag ccaagcaaca aggugcccga aacaugcaga cucugguucu acagagcccc 4860
aacgagaaug augacacccc cgucgacgag gcguugggua gaguucucuc ccccgcugcg 4920
gucgaugagg cgcuugucga ccucacucca gaggccgacc cgguuggccg uuuggcuauu 4980
cuugccaagc uaggucuugc ccuagcugcg gucaccccug gucugauaau cuuggcagug 5040
ggacucuaca gguacuucuc uggcucugau gcagaccaag aagaaacaga aagugaggga 5100
ucugucaagg cacccaggag cgaaaaugcu uaugacggcc cgaagaaaaa cucuaagccc 5160
ccuggagcac ucucucucau ggaaaugcaa cagcccaacg uggacauggg cuuugaggcu 5220
gcggucgcua agaaaguggu cguccccauu accuucaugg uucccaacag accuucuggg 5280
cuuacacagu ccgcucuucu ggugaccggc cggaccuucc uaaucaauga acauacaugg 5340
uccaaucccu ccuggaccag cuucacaauc cgcggugagg uacacacucg ugaugagccc 5400
uuccaaacgg uucauuucac ucaccacggu auucccacag aucugaugau gguacgucuc 5460
ggaccgggca auucuuuccc uaacaaucua gacaaguuug gacuugacca gaugccggca 5520
cgcaacuccc gugugguugg cguuucgucc aguuacggaa acuucuucuu cucuggaaau 5580
uuccucggau uuguugauuc caucaccucu gaacaaggaa cuuacgcaag acucuuuagg 5640
uacaggguga cgaccuacaa aggauggugc ggcucggccc uggucuguga ggccgguggc 5700
guccgacgca ucauuggccu gcauucugcu ggcgccgccg guaucggcgc cgggaccuau 5760
aucucaaaau uaggacuaau caaagcccug aaacaccucg gugaaccuuu ggccacaaug 5820
caaggacuga ugacugaauu agagccugga aucaccguac auguaccccg gaaauccaaa 5880
uugagaaaga cgaccgcaca cgcgguguac aaaccggagu uugagccugc uguguuguca 5940
aaauuugauc ccagacugaa caaggauguu gacuuggaug aaguaauuug gucuaaacac 6000
acugccaaug ucccuuacca accuccuuug uucuacacau acaugucaga guacgcucau 6060
cgagucuucu ccuucuuggg gaaagacaau gacauucuga ccgucaaaga agcaauucug 6120
ggcauccccg gacuagaccc cauggauccc cacacagcuc cgggucugcc uuacgccauc 6180
aacggccuuc gacguacuga ucucgucgau uuugugaacg guacaguaga ugcggcgcug 6240
gcuguacaaa uccagaaauu cuuagacggu gacuacucug accaugucuu ccaaacuuuu 6300
cugaaagaug agaucagacc cucagagaaa guccgagcgg gaaaaacccg cauuguugau 6360
gugcccuccc uggcgcauug cauugugggc agaauguugc uugggcgcuu ugcugccaag 6420
uuucaauccc auccuggcuu ucuccucggc ucugcuaucg ggucugaccc ugauguuuuc 6480
uggaccguca uaggggcuca acucgagggg agaaagaaca cguaugacgu ggacuacagu 6540
gccuuugacu cuucacacgg cacuggcucc uucgaggcuc ucaucucuca cuuuuucacc 6600
guggacaaug guuuuagccc ugcgcuggga ccguaucuca gaucccuggc ugucucggug 6660
cacgcuuacg gcgagcgucg caucaagauu accgguggcc uccccuccgg uugugccgcg 6720
accagccugc ugaacacagu gcucaacaau gugaucauca ggacugcucu ggcauugacu 6780
uacaaggaau uugaauauga caugguugau aucaucgccu acggugacga ccuucugguu 6840
ggcacggauu acgaucugga cuucaaugag guggcacgac gcgcugccaa guugggguau 6900
aagaugacuc cugccaacaa ggguucuguc uucccuccga cuuccucucu uuccgaugcu 6960
guuuuucuaa agcgcaaauu cguccaaaac aacgacggcu uauacaaacc aguuauggau 7020
uuaaagaauu uggaagccau gcucuccuac uucaaaccag gaacacuacu cgagaagcug 7080
caaucuguuu cuauguuggc ucaacauucu ggaaaagaag aauaugauag auugaugcac 7140
cccuucgcug acuacggugc cguaccgagu cacgaguacc ugcaggcaag auggagggcc 7200
uuguucgacu gacccagaua gcccaaggcg cuucggugcu gccggcgauu cugggagaac 7260
ucagucggaa cagaaaaggg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 7310
<210> 14
<211> 7310
<212> RNA
<213> 塞内卡病毒
<400> 14
uuugaaaugg ggggcugggc ccugaugccc aguccuuccu uuccccuucc gggggguuaa 60
ccggcugugu uugcuagagg cacagagggg caacauccaa ccugcuuuug cggggaacgg 120
ugcggcuccg auuccugcgu cgccaaaggu guuagcgcac ccaaacggcg caccuaccaa 180
uguuauuggu guggucugcg aguucuagcc uacucguuuc ucccccgacc auucacucac 240
ccacgaaaag uguguuguaa ccauaagauu uaacccccgc acgggaugug cgauaaccgu 300
aagacuggcu caagcgcgga aagcgcugua accacaugcu guuagucccu uuauggcugc 360
aagauggcua cccaccucgg aucacugaac uggagcucga cccuccuuag uaagggaacc 420
gagaggccuu cgugcaacaa gcuccgacac agaguccacg ugacugcuac caccaugagu 480
acaugguucu ccccucucga cccaggacuu cuuuuugaau auccacggcu cgauccagag 540
gguggggcau gaccccuagc auagcgagcu acagcgggaa cuguagcuag gccuuagcgu 600
gccuuggaua cugccugaua gggcgacggc cuagucgugu cgguucuaua gguagcacau 660
acaaauaugc agaacucuca uuuuucuuuc gauacagccu cuggcaccuu ugaagaugua 720
accggaacaa aagucaagau cguugaauac cccagaucgg ugaacaaugg uguuuacgau 780
ucgucuacuc auuuggagau acugaaccua cagggugaaa uugaaauuuu aaggucuuuc 840
aaugaauacc aaauucgcgc cgccaaacaa caacucggac uggacaucgu guacgaacua 900
caggguaaug uucagacaac gucaaagaau gauuuugauu cccguggcaa uaaugguaac 960
augaccuuca auuacuacgc aaacacuuau cagaauucag uagacuucuc gaccuccucg 1020
ucggcgucag gcgccggacc cgggaacucc cggggcggau uagcgggucu ccucacaaau 1080
uucaguggaa ucuugaaccc ucuuggcuac cucaaagauc acaacaccga agaaauggaa 1140
aacucugcug aucgagucac aacgcaaacg gcgggcaaca cugccauaaa cacgcaauca 1200
ucauugggug uguugugugc cuacguugaa gacccgacca aaucugaucc uccguccagc 1260
agcacagauc aacccaccac cacuuucacu gccaucgaca ggugguacac uggacgucuc 1320
aauucuugga caaaagcugu aaaaaccuuc ucuuuucagg ccgucccgcu ucccggggcc 1380
uuucugucua ggcagggagg ccucaacgga ggggccuuca cagcuacccu acauagacac 1440
uuuuugauga agugcgggug gcaggugcag guccaaugua auuugacaca auuccaccaa 1500
ggcgcucuuc uuguugccau gguuccugaa accacccuug augucaagcc cgacgguaag 1560
gcaaagagcu uacaggagcu gaaugaagaa cagugggugg aaaugucuga cgauuaccgg 1620
accgggaaaa acaugccuuu ucagucucuu ggcacauacu aucggccccc uaacuggacu 1680
ugggguccca auuucaucaa ccccuaucaa guaacgguuu ucccacacca aauucugaac 1740
gcgagaaccu cuaccucggu agacauaaac gucccauaca ucggggagac ccccacgcaa 1800
uccucagaga cacagaacuc cuggacccuc cucguuaugg ugcucguucc ccuagacuau 1860
aaggaaggag ccacaacuga cccagaaauu acauuuucug uaaggccuac aagucccuac 1920
uucaaugggc uucgcaaccg cuacacggcc gggacggacg aagaacaggg gcccauuccu 1980
acggcaccca gagaaaauuc gcuuauguuu cucucaaccc ucccugacga cacugucccu 2040
gcuuacggga augugcguac cccuccuguc aauuaccucc cuggugaaau aaccgaccuu 2100
uugcaacugg cccgcauacc cacucucaug gcauuugagc gggugccuga acccgugccu 2160
gccucagaca cauaugugcc cuacguugcc guucccaccc aguucgauga caggccucuc 2220
aucuccuucc cgaucacccu uucagauccc gucuaucaga acacccuggu uggcgccauc 2280
aguucaaauu ucgccaauua ccgugggugu auccaaauca cucugacauu uuguggaccc 2340
augauggcga gagggaaauu ccugcucucg uauucucccc caaauggaac gcaaccacag 2400
acucuuuccg aagcuaugca gugcacauac ucuauuuggg acauaggcuu gaacucuagu 2460
uggaccuucg ucguccccua caucucgccc agugacuacc gugaaacucg agccauuacc 2520
aacucgguuu acuccgcuga ugguugguuu agccugcaca aguugaccaa aauuacucua 2580
ccaccugacu guccgcaaag ucccugcauu cucuuuuucg cuucugcugg ugaggauuac 2640
acucuccguc uccccguuga uuguaauccu uccuaugugu uccacuccac cgacaacgcc 2700
gagaccgggg uuauugaggc ggguaacacu gacaccgauu ucucugguga acuggcggcu 2760
ccuggcucua accacacuaa ugucaaguuc cuguuugauc gaucucgauu auugaaugua 2820
aucaagguac uggagaagga cgccguuuuc ccccgcccuu ucccuacaca agaaggugcg 2880
cagcaggaug augguuacuu uugucuucug accccccgcc caacagucgc uucccgaccc 2940
gccacucguu ucggccugua cgccaauccg uccggcagug guguucuugc uaacacuuca 3000
cuggacuuca auuuuuauag cuuggccugu uucacuuacu uuagaucgga ccuugagguu 3060
acgguggucu cacuagagcc ggaucuggaa uuugcuguag ggugguuucc uucuggcagu 3120
gaauaccagg cuuccagcuu ugucuacgac cagcugcaug ugcccuucca cuuuacuggg 3180
cgcacucccc gcgcuuucgc uagcaagggu gggaagguau cuuucgugcu cccuuggaac 3240
ucugucucgu cugugcuccc cgugcgcugg gggggggcuu ccaagcucuc uucugcuacg 3300
cggggucuac cggcgcaugc ugauuggggg acuauuuacg ccuuuguccc ccguccuaau 3360
gagaagaaaa gcaccgcugu aaaacacgug gccguguaca uucgguacaa gaacgcacgu 3420
gccuggugcc ccagcaugcu ucccuuucgc agcuacaagc agaagaugcu gaugcaaucu 3480
ggcgauaucg agaccaaucc ugguccugcu ucugacaacc caauuuugga guuucuugaa 3540
gcagaaaaug aucuagucac ucuggccucu cucuggaaga uggugcacuc uguucaacag 3600
accuggagaa aguaugugaa gaacgaugau uuuuggccca auuuacucag cgagcuagug 3660
ggggaaggcu cugucgccuu ggccgccacg cuauccaacc aagcuucagu aaaggcucuu 3720
uugggccugc acuuucucuc ucgggggcuc aauuacacug acuuuuacuc uuuacugaua 3780
gagaaaugcu cuaguuucuu uaccguagaa ccaccuccuc caccagcuga aaaccugaug 3840
accaagcccu cagugaaguc gaaauuccga aaacuguuua agaugcaagg acccauggac 3900
aaagucaaag acuggaacca aauagcugcc ggcuugaaga auuuucaauu uguucgugac 3960
cuagucaaag agguggucga uuggcugcag gccuggauca acaaagagaa agccagcccu 4020
guccuccagu accaguugga gaugaagaag cucgggccug uggccuuggc ucaugacgcu 4080
uucauggcug guuccgggcc cccucuuagc gacgaccaga uugaauaccu ccagaaccuc 4140
aaaucucuug cccuaacacu ggggaagacu aauuuggccc aaagucucac cacuaugauc 4200
aaugccaaac aaaguucagc ccaacgaguu gaacccguug uggugguccu uagaggcaag 4260
ccgggaugcg gcaagagcuu ggccucuacg uugauugccc aggcuguguc caagcgccuc 4320
uauggcuccc aaaguguaua uucucuuccc ccagauccag auuucuucga uggauacaaa 4380
ggacaguucg ugaccuugau ggaugauuug ggacaaaacc cggauggaca agauuucucc 4440
accuuuuguc agaugguguc gaccgcccaa uuucucccca acauggcgga ccuugcagag 4500
aaagggcguc ccuuuaccuc caaucucauc auugcaacua caaaucuccc ccacuucagu 4560
ccugucacca uugcugaucc uucugcaguc ucucgccgua ucaacuacga ucugacucua 4620
gaaguaucug aggccuacaa gaaacacaca cggcugaauu uugacuuggc uuucaggcgc 4680
acagacgccc cccccauuua uccuuuugcu gcccaugugc ccuuugugga cguagcugug 4740
cgcuucaaaa auggucacca gaauuuuaau cuccuagagu uggucgauuc cauuuguaca 4800
gacauucgag ccaagcaaca aggugcccga aacaugcaga cucugguucu acagagcccc 4860
aacgagaaug augacacccc cgucgacgag gcguugggua gaguucucuc ccccgcugcg 4920
gucgaugagg cgcuugucga ccucacucca gaggccgacc cgguuggccg uuuggcuauu 4980
cuugccaagc uaggucuugc ccuagcugcg gucaccccug gucugauaau cuuggcagug 5040
ggacucuaca gguacuucuc uggcucugau gcagaccaag aagaaacaga aagugaggga 5100
ucugucaagg cacccaggag cgaaaaugcu uaugacggcc cgaagaaaaa cucuaagccc 5160
ccuggagcac ucucucucau ggaaaugcaa cagcccaacg uggacauggg cuuugaggcu 5220
gcggucgcua agaaaguggu cguccccauu accuucaugg uucccaacag accuucuggg 5280
cuuacacagu ccgcucuucu ggugaccggc cggaccuucc uaaucaauga acauacaugg 5340
uccaaucccu ccuggaccag cuucacaauc cgcggugagg uacacacucg ugaugagccc 5400
uuccaaacgg uucauuucac ucaccacggu auucccacag aucugaugau gguacgucuc 5460
ggaccgggca auucuuuccc uaacaaucua gacaaguuug gacuugacca gaugccggca 5520
cgcaacuccc gugugguugg cguuucgucc aguuacggaa acuucuucuu cucuggaaau 5580
uuccucggau uuguugauuc caucaccucu gaacaaggaa cuuacgcaag acucuuuagg 5640
uacaggguga cgaccuacaa aggauggugc ggcucggccc uggucuguga ggccgguggc 5700
guccgacgca ucauuggccu gcauucugcu ggcgccgccg guaucggcgc cgggaccuau 5760
aucucaaaau uaggacuaau caaagcccug aaacaccucg gugaaccuuu ggccacaaug 5820
caaggacuga ugacugaauu agagccugga aucaccguac auguaccccg gaaauccaaa 5880
uugagaaaga cgaccgcaca cgcgguguac aaaccggagu uugagccugc uguguuguca 5940
aaauuugauc ccagacugaa caaggauguu gacuuggaug aaguaauuug gucuaaacac 6000
acugccaaug ucccuuacca accuccuuug uucuacacau acaugucaga guacgcucau 6060
cgagucuucu ccuucuuggg gaaagacaau gacauucuga ccgucaaaga agcaauucug 6120
ggcauccccg gacuagaccc cauggauccc cacacagcuc cgggucugcc uuacgccauc 6180
aacggccuuc gacguacuga ucucgucgau uuugugaacg guacaguaga ugcggcgcug 6240
gcuguacaaa uccagaaauu cuuagacggu gacuacucug accaugucuu ccaaacuuuu 6300
cugaaagaug agaucagacc cucagagaaa guccgagcgg gaaaaacccg cauuguugau 6360
gugcccuccc uggcgcauug cauugugggc agaauguugc uugggcgcuu ugcugccaag 6420
uuucaauccc auccuggcuu ucuccucggc ucugcuaucg ggucugaccc ugauguuuuc 6480
uggaccguca uaggggcuca acucgagggg agaaagaaca cguaugacgu ggacuacagu 6540
gccuuugacu cuucacacgg cacuggcucc uucgaggcuc ucaucucuca cuuuuucacc 6600
guggacaaug guuuuagccc ugcgcuggga ccguaucuca gaucccuggc ugucucggug 6660
cacgcuuacg gcgagcgucg caucaagauu accgguggcc uccccuccgg uugugccgcg 6720
accagccugc ugaacacagu gcucaacaau gugaucauca ggacugcucu ggcauugacu 6780
uacaaggaau uugaauauga caugguugau aucaucgccu acggugacga ccuucugguu 6840
ggcacggauu acgaucugga cuucaaugag guggcacgac gcgcugccaa guugggguau 6900
aagaugacuc cugccaacaa ggguucuguc uucccuccga cuuccucucu uuccgaugcu 6960
guuuuucuaa agcgcaaauu cguccaaaac aacgacggcu uauacaaacc aguuauggau 7020
uuaaagaauu uggaagccau gcucuccuac uucaaaccag gaacacuacu cgagaagcug 7080
caaucuguuu cuauguuggc ucaacauucu ggaaaagaag aauaugauag auugaugcac 7140
cccuucgcug acuacggugc cguaccgagu cacgaguacc ugcaggcaag auggagggcc 7200
uuguucgacu gacccagaua gcccaaggcg cuucggugcu gccggcgauu cugggagaac 7260
ucagucggaa cagaaaaggg aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 7310
<210> 15
<211> 2181
<212> PRT
<213> 塞内卡病毒
<400> 15
Met Gln Asn Ser His Phe Ser Phe Asp Thr Ala Ser Gly Thr Phe Glu
1 5 10 15
Asp Val Thr Gly Thr Lys Val Lys Ile Val Glu Tyr Pro Arg Ser Val
20 25 30
Asn Asn Gly Val Tyr Asp Ser Ser Thr His Leu Glu Ile Leu Asn Leu
35 40 45
Gln Gly Glu Ile Glu Ile Leu Arg Ser Phe Asn Glu Tyr Gln Ile Arg
50 55 60
Ala Ala Lys Gln Gln Leu Gly Leu Asp Ile Val Tyr Glu Leu Gln Gly
65 70 75 80
Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly Asn Asn
85 90 95
Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn Ser Val
100 105 110
Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly Asn Ser
115 120 125
Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile Leu Asn
130 135 140
Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu Asn Ser
145 150 155 160
Ala Asp Arg Val Thr Thr Gln Thr Ala Gly Asn Thr Ala Ile Asn Thr
165 170 175
Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro Thr Lys
180 185 190
Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr Phe Thr
195 200 205
Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr Lys Ala
210 215 220
Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala Phe Leu
225 230 235 240
Ser Arg Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr Leu His
245 250 255
Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln Cys Asn
260 265 270
Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val Pro Glu
275 280 285
Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu Gln Glu
290 295 300
Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg Thr Gly
305 310 315 320
Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro Pro Asn
325 330 335
Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr Val Phe
340 345 350
Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp Ile Asn
355 360 365
Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr Gln Asn
370 375 380
Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr Lys Glu
385 390 395 400
Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro Thr Ser
405 410 415
Pro Tyr Phe Asn Gly Leu Arg Asn Arg Tyr Thr Ala Gly Thr Asp Glu
420 425 430
Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu Met Phe
435 440 445
Leu Ser Thr Leu Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn Val Arg
450 455 460
Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu Leu Gln
465 470 475 480
Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Glu Arg Val Pro Glu Pro
485 490 495
Val Pro Ala Ser Asp Thr Tyr Val Pro Tyr Val Ala Val Pro Thr Gln
500 505 510
Phe Asp Asp Arg Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser Asp Pro
515 520 525
Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe Ala Asn
530 535 540
Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro Met Met
545 550 555 560
Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly Thr Gln
565 570 575
Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile Trp Asp
580 585 590
Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Val Pro Tyr Ile Ser Pro
595 600 605
Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr Ser Ala
610 615 620
Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu Pro Pro
625 630 635 640
Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala Gly Glu
645 650 655
Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr Val Phe
660 665 670
His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly Asn Thr
675 680 685
Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn His Thr
690 695 700
Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val Ile Lys
705 710 715 720
Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr Gln Glu
725 730 735
Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro Arg Pro
740 745 750
Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Ala Asn Pro
755 760 765
Ser Gly Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn Phe Tyr
770 775 780
Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val Thr Val
785 790 795 800
Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe Pro Ser
805 810 815
Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu His Val
820 825 830
Pro Phe His Phe Thr Gly Arg Thr Pro Arg Ala Phe Ala Ser Lys Gly
835 840 845
Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser Val Leu
850 855 860
Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr Arg Gly
865 870 875 880
Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Val Pro Arg
885 890 895
Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val Tyr Ile
900 905 910
Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro Phe Arg
915 920 925
Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Ile Glu Thr Asn
930 935 940
Pro Gly Pro Ala Ser Asp Asn Pro Ile Leu Glu Phe Leu Glu Ala Glu
945 950 955 960
Asn Asp Leu Val Thr Leu Ala Ser Leu Trp Lys Met Val His Ser Val
965 970 975
Gln Gln Thr Trp Arg Lys Tyr Val Lys Asn Asp Asp Phe Trp Pro Asn
980 985 990
Leu Leu Ser Glu Leu Val Gly Glu Gly Ser Val Ala Leu Ala Ala Thr
995 1000 1005
Leu Ser Asn Gln Ala Ser Val Lys Ala Leu Leu Gly Leu His Phe
1010 1015 1020
Leu Ser Arg Gly Leu Asn Tyr Thr Asp Phe Tyr Ser Leu Leu Ile
1025 1030 1035
Glu Lys Cys Ser Ser Phe Phe Thr Val Glu Pro Pro Pro Pro Pro
1040 1045 1050
Ala Glu Asn Leu Met Thr Lys Pro Ser Val Lys Ser Lys Phe Arg
1055 1060 1065
Lys Leu Phe Lys Met Gln Gly Pro Met Asp Lys Val Lys Asp Trp
1070 1075 1080
Asn Gln Ile Ala Ala Gly Leu Lys Asn Phe Gln Phe Val Arg Asp
1085 1090 1095
Leu Val Lys Glu Val Val Asp Trp Leu Gln Ala Trp Ile Asn Lys
1100 1105 1110
Glu Lys Ala Ser Pro Val Leu Gln Tyr Gln Leu Glu Met Lys Lys
1115 1120 1125
Leu Gly Pro Val Ala Leu Ala His Asp Ala Phe Met Ala Gly Ser
1130 1135 1140
Gly Pro Pro Leu Ser Asp Asp Gln Ile Glu Tyr Leu Gln Asn Leu
1145 1150 1155
Lys Ser Leu Ala Leu Thr Leu Gly Lys Thr Asn Leu Ala Gln Ser
1160 1165 1170
Leu Thr Thr Met Ile Asn Ala Lys Gln Ser Ser Ala Gln Arg Val
1175 1180 1185
Glu Pro Val Val Val Val Leu Arg Gly Lys Pro Gly Cys Gly Lys
1190 1195 1200
Ser Leu Ala Ser Thr Leu Ile Ala Gln Ala Val Ser Lys Arg Leu
1205 1210 1215
Tyr Gly Ser Gln Ser Val Tyr Ser Leu Pro Pro Asp Pro Asp Phe
1220 1225 1230
Phe Asp Gly Tyr Lys Gly Gln Phe Val Thr Leu Met Asp Asp Leu
1235 1240 1245
Gly Gln Asn Pro Asp Gly Gln Asp Phe Ser Thr Phe Cys Gln Met
1250 1255 1260
Val Ser Thr Ala Gln Phe Leu Pro Asn Met Ala Asp Leu Ala Glu
1265 1270 1275
Lys Gly Arg Pro Phe Thr Ser Asn Leu Ile Ile Ala Thr Thr Asn
1280 1285 1290
Leu Pro His Phe Ser Pro Val Thr Ile Ala Asp Pro Ser Ala Val
1295 1300 1305
Ser Arg Arg Ile Asn Tyr Asp Leu Thr Leu Glu Val Ser Glu Ala
1310 1315 1320
Tyr Lys Lys His Thr Arg Leu Asn Phe Asp Leu Ala Phe Arg Arg
1325 1330 1335
Thr Asp Ala Pro Pro Ile Tyr Pro Phe Ala Ala His Val Pro Phe
1340 1345 1350
Val Asp Val Ala Val Arg Phe Lys Asn Gly His Gln Asn Phe Asn
1355 1360 1365
Leu Leu Glu Leu Val Asp Ser Ile Cys Thr Asp Ile Arg Ala Lys
1370 1375 1380
Gln Gln Gly Ala Arg Asn Met Gln Thr Leu Val Leu Gln Ser Pro
1385 1390 1395
Asn Glu Asn Asp Asp Thr Pro Val Asp Glu Ala Leu Gly Arg Val
1400 1405 1410
Leu Ser Pro Ala Ala Val Asp Glu Ala Leu Val Asp Leu Thr Pro
1415 1420 1425
Glu Ala Asp Pro Val Gly Arg Leu Ala Ile Leu Ala Lys Leu Gly
1430 1435 1440
Leu Ala Leu Ala Ala Val Thr Pro Gly Leu Ile Ile Leu Ala Val
1445 1450 1455
Gly Leu Tyr Arg Tyr Phe Ser Gly Ser Asp Ala Asp Gln Glu Glu
1460 1465 1470
Thr Glu Ser Glu Gly Ser Val Lys Ala Pro Arg Ser Glu Asn Ala
1475 1480 1485
Tyr Asp Gly Pro Lys Lys Asn Ser Lys Pro Pro Gly Ala Leu Ser
1490 1495 1500
Leu Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala
1505 1510 1515
Ala Val Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro
1520 1525 1530
Asn Arg Pro Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Thr Gly
1535 1540 1545
Arg Thr Phe Leu Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp
1550 1555 1560
Thr Ser Phe Thr Ile Arg Gly Glu Val His Thr Arg Asp Glu Pro
1565 1570 1575
Phe Gln Thr Val His Phe Thr His His Gly Ile Pro Thr Asp Leu
1580 1585 1590
Met Met Val Arg Leu Gly Pro Gly Asn Ser Phe Pro Asn Asn Leu
1595 1600 1605
Asp Lys Phe Gly Leu Asp Gln Met Pro Ala Arg Asn Ser Arg Val
1610 1615 1620
Val Gly Val Ser Ser Ser Tyr Gly Asn Phe Phe Phe Ser Gly Asn
1625 1630 1635
Phe Leu Gly Phe Val Asp Ser Ile Thr Ser Glu Gln Gly Thr Tyr
1640 1645 1650
Ala Arg Leu Phe Arg Tyr Arg Val Thr Thr Tyr Lys Gly Trp Cys
1655 1660 1665
Gly Ser Ala Leu Val Cys Glu Ala Gly Gly Val Arg Arg Ile Ile
1670 1675 1680
Gly Leu His Ser Ala Gly Ala Ala Gly Ile Gly Ala Gly Thr Tyr
1685 1690 1695
Ile Ser Lys Leu Gly Leu Ile Lys Ala Leu Lys His Leu Gly Glu
1700 1705 1710
Pro Leu Ala Thr Met Gln Gly Leu Met Thr Glu Leu Glu Pro Gly
1715 1720 1725
Ile Thr Val His Val Pro Arg Lys Ser Lys Leu Arg Lys Thr Thr
1730 1735 1740
Ala His Ala Val Tyr Lys Pro Glu Phe Glu Pro Ala Val Leu Ser
1745 1750 1755
Lys Phe Asp Pro Arg Leu Asn Lys Asp Val Asp Leu Asp Glu Val
1760 1765 1770
Ile Trp Ser Lys His Thr Ala Asn Val Pro Tyr Gln Pro Pro Leu
1775 1780 1785
Phe Tyr Thr Tyr Met Ser Glu Tyr Ala His Arg Val Phe Ser Phe
1790 1795 1800
Leu Gly Lys Asp Asn Asp Ile Leu Thr Val Lys Glu Ala Ile Leu
1805 1810 1815
Gly Ile Pro Gly Leu Asp Pro Met Asp Pro His Thr Ala Pro Gly
1820 1825 1830
Leu Pro Tyr Ala Ile Asn Gly Leu Arg Arg Thr Asp Leu Val Asp
1835 1840 1845
Phe Val Asn Gly Thr Val Asp Ala Ala Leu Ala Val Gln Ile Gln
1850 1855 1860
Lys Phe Leu Asp Gly Asp Tyr Ser Asp His Val Phe Gln Thr Phe
1865 1870 1875
Leu Lys Asp Glu Ile Arg Pro Ser Glu Lys Val Arg Ala Gly Lys
1880 1885 1890
Thr Arg Ile Val Asp Val Pro Ser Leu Ala His Cys Ile Val Gly
1895 1900 1905
Arg Met Leu Leu Gly Arg Phe Ala Ala Lys Phe Gln Ser His Pro
1910 1915 1920
Gly Phe Leu Leu Gly Ser Ala Ile Gly Ser Asp Pro Asp Val Phe
1925 1930 1935
Trp Thr Val Ile Gly Ala Gln Leu Glu Gly Arg Lys Asn Thr Tyr
1940 1945 1950
Asp Val Asp Tyr Ser Ala Phe Asp Ser Ser His Gly Thr Gly Ser
1955 1960 1965
Phe Glu Ala Leu Ile Ser His Phe Phe Thr Val Asp Asn Gly Phe
1970 1975 1980
Ser Pro Ala Leu Gly Pro Tyr Leu Arg Ser Leu Ala Val Ser Val
1985 1990 1995
His Ala Tyr Gly Glu Arg Arg Ile Lys Ile Thr Gly Gly Leu Pro
2000 2005 2010
Ser Gly Cys Ala Ala Thr Ser Leu Leu Asn Thr Val Leu Asn Asn
2015 2020 2025
Val Ile Ile Arg Thr Ala Leu Ala Leu Thr Tyr Lys Glu Phe Glu
2030 2035 2040
Tyr Asp Met Val Asp Ile Ile Ala Tyr Gly Asp Asp Leu Leu Val
2045 2050 2055
Gly Thr Asp Tyr Asp Leu Asp Phe Asn Glu Val Ala Arg Arg Ala
2060 2065 2070
Ala Lys Leu Gly Tyr Lys Met Thr Pro Ala Asn Lys Gly Ser Val
2075 2080 2085
Phe Pro Pro Thr Ser Ser Leu Ser Asp Ala Val Phe Leu Lys Arg
2090 2095 2100
Lys Phe Val Gln Asn Asn Asp Gly Leu Tyr Lys Pro Val Met Asp
2105 2110 2115
Leu Lys Asn Leu Glu Ala Met Leu Ser Tyr Phe Lys Pro Gly Thr
2120 2125 2130
Leu Leu Glu Lys Leu Gln Ser Val Ser Met Leu Ala Gln His Ser
2135 2140 2145
Gly Lys Glu Glu Tyr Asp Arg Leu Met His Pro Phe Ala Asp Tyr
2150 2155 2160
Gly Ala Val Pro Ser His Glu Tyr Leu Gln Ala Arg Trp Arg Ala
2165 2170 2175
Leu Phe Asp
2180
<210> 16
<211> 2181
<212> PRT
<213> 塞内卡病毒
<400> 16
Met Gln Asn Ser His Phe Ser Phe Asp Thr Ala Ser Gly Thr Phe Glu
1 5 10 15
Asp Val Thr Gly Thr Lys Val Lys Ile Val Glu Tyr Pro Arg Ser Val
20 25 30
Asn Asn Gly Val Tyr Asp Ser Ser Thr His Leu Glu Ile Leu Asn Leu
35 40 45
Gln Gly Glu Ile Glu Ile Leu Arg Ser Phe Asn Glu Tyr Gln Ile Arg
50 55 60
Ala Ala Lys Gln Gln Leu Gly Leu Asp Ile Val Tyr Glu Leu Gln Gly
65 70 75 80
Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly Asn Asn
85 90 95
Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn Ser Val
100 105 110
Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly Asn Ser
115 120 125
Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile Leu Asn
130 135 140
Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu Asn Ser
145 150 155 160
Ala Asp Arg Val Thr Thr Gln Thr Ala Gly Asn Thr Ala Ile Asn Thr
165 170 175
Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro Thr Lys
180 185 190
Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr Phe Thr
195 200 205
Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr Lys Ala
210 215 220
Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala Phe Leu
225 230 235 240
Ser Arg Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr Leu His
245 250 255
Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln Cys Asn
260 265 270
Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val Pro Glu
275 280 285
Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu Gln Glu
290 295 300
Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg Thr Gly
305 310 315 320
Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro Pro Asn
325 330 335
Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr Val Phe
340 345 350
Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp Ile Asn
355 360 365
Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr Gln Asn
370 375 380
Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr Lys Glu
385 390 395 400
Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro Thr Ser
405 410 415
Pro Tyr Phe Asn Gly Leu Arg Asn Arg Tyr Thr Ala Gly Thr Asp Glu
420 425 430
Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu Met Phe
435 440 445
Leu Ser Thr Leu Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn Val Arg
450 455 460
Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu Leu Gln
465 470 475 480
Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Glu Arg Val Pro Glu Pro
485 490 495
Val Pro Ala Ser Asp Thr Tyr Val Pro Tyr Val Ala Val Pro Thr Gln
500 505 510
Phe Asp Asp Arg Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser Asp Pro
515 520 525
Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe Ala Asn
530 535 540
Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro Met Met
545 550 555 560
Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly Thr Gln
565 570 575
Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile Trp Asp
580 585 590
Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Val Pro Tyr Ile Ser Pro
595 600 605
Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr Ser Ala
610 615 620
Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu Pro Pro
625 630 635 640
Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala Gly Glu
645 650 655
Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr Val Phe
660 665 670
His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly Asn Thr
675 680 685
Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn His Thr
690 695 700
Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val Ile Lys
705 710 715 720
Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr Gln Glu
725 730 735
Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro Arg Pro
740 745 750
Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Ala Asn Pro
755 760 765
Ser Gly Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn Phe Tyr
770 775 780
Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val Thr Val
785 790 795 800
Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe Pro Ser
805 810 815
Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu His Val
820 825 830
Pro Phe His Phe Thr Gly Arg Thr Pro Arg Ala Phe Ala Ser Lys Gly
835 840 845
Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser Val Leu
850 855 860
Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr Arg Gly
865 870 875 880
Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Val Pro Arg
885 890 895
Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val Tyr Ile
900 905 910
Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro Phe Arg
915 920 925
Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Ile Glu Thr Asn
930 935 940
Pro Gly Pro Ala Ser Asp Asn Pro Ile Leu Glu Phe Leu Glu Ala Glu
945 950 955 960
Asn Asp Leu Val Thr Leu Ala Ser Leu Trp Lys Met Val His Ser Val
965 970 975
Gln Gln Thr Trp Arg Lys Tyr Val Lys Asn Asp Asp Phe Trp Pro Asn
980 985 990
Leu Leu Ser Glu Leu Val Gly Glu Gly Ser Val Ala Leu Ala Ala Thr
995 1000 1005
Leu Ser Asn Gln Ala Ser Val Lys Ala Leu Leu Gly Leu His Phe
1010 1015 1020
Leu Ser Arg Gly Leu Asn Tyr Thr Asp Phe Tyr Ser Leu Leu Ile
1025 1030 1035
Glu Lys Cys Ser Ser Phe Phe Thr Val Glu Pro Pro Pro Pro Pro
1040 1045 1050
Ala Glu Asn Leu Met Thr Lys Pro Ser Val Lys Ser Lys Phe Arg
1055 1060 1065
Lys Leu Phe Lys Met Gln Gly Pro Met Asp Lys Val Lys Asp Trp
1070 1075 1080
Asn Gln Ile Ala Ala Gly Leu Lys Asn Phe Gln Phe Val Arg Asp
1085 1090 1095
Leu Val Lys Glu Val Val Asp Trp Leu Gln Ala Trp Ile Asn Lys
1100 1105 1110
Glu Lys Ala Ser Pro Val Leu Gln Tyr Gln Leu Glu Met Lys Lys
1115 1120 1125
Leu Gly Pro Val Ala Leu Ala His Asp Ala Phe Met Ala Gly Ser
1130 1135 1140
Gly Pro Pro Leu Ser Asp Asp Gln Ile Glu Tyr Leu Gln Asn Leu
1145 1150 1155
Lys Ser Leu Ala Leu Thr Leu Gly Lys Thr Asn Leu Ala Gln Ser
1160 1165 1170
Leu Thr Thr Met Ile Asn Ala Lys Gln Ser Ser Ala Gln Arg Val
1175 1180 1185
Glu Pro Val Val Val Val Leu Arg Gly Lys Pro Gly Cys Gly Lys
1190 1195 1200
Ser Leu Ala Ser Thr Leu Ile Ala Gln Ala Val Ser Lys Arg Leu
1205 1210 1215
Tyr Gly Ser Gln Ser Val Tyr Ser Leu Pro Pro Asp Pro Asp Phe
1220 1225 1230
Phe Asp Gly Tyr Lys Gly Gln Phe Val Thr Leu Met Asp Asp Leu
1235 1240 1245
Gly Gln Asn Pro Asp Gly Gln Asp Phe Ser Thr Phe Cys Gln Met
1250 1255 1260
Val Ser Thr Ala Gln Phe Leu Pro Asn Met Ala Asp Leu Ala Glu
1265 1270 1275
Lys Gly Arg Pro Phe Thr Ser Asn Leu Ile Ile Ala Thr Thr Asn
1280 1285 1290
Leu Pro His Phe Ser Pro Val Thr Ile Ala Asp Pro Ser Ala Val
1295 1300 1305
Ser Arg Arg Ile Asn Tyr Asp Leu Thr Leu Glu Val Ser Glu Ala
1310 1315 1320
Tyr Lys Lys His Thr Arg Leu Asn Phe Asp Leu Ala Phe Arg Arg
1325 1330 1335
Thr Asp Ala Pro Pro Ile Tyr Pro Phe Ala Ala His Val Pro Phe
1340 1345 1350
Val Asp Val Ala Val Arg Phe Lys Asn Gly His Gln Asn Phe Asn
1355 1360 1365
Leu Leu Glu Leu Val Asp Ser Ile Cys Thr Asp Ile Arg Ala Lys
1370 1375 1380
Gln Gln Gly Ala Arg Asn Met Gln Thr Leu Val Leu Gln Ser Pro
1385 1390 1395
Asn Glu Asn Asp Asp Thr Pro Val Asp Glu Ala Leu Gly Arg Val
1400 1405 1410
Leu Ser Pro Ala Ala Val Asp Glu Ala Leu Val Asp Leu Thr Pro
1415 1420 1425
Glu Ala Asp Pro Val Gly Arg Leu Ala Ile Leu Ala Lys Leu Gly
1430 1435 1440
Leu Ala Leu Ala Ala Val Thr Pro Gly Leu Ile Ile Leu Ala Val
1445 1450 1455
Gly Leu Tyr Arg Tyr Phe Ser Gly Ser Asp Ala Asp Gln Glu Glu
1460 1465 1470
Thr Glu Ser Glu Gly Ser Val Lys Ala Pro Arg Ser Glu Asn Ala
1475 1480 1485
Tyr Asp Gly Pro Lys Lys Asn Ser Lys Pro Pro Gly Ala Leu Ser
1490 1495 1500
Leu Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala
1505 1510 1515
Ala Val Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro
1520 1525 1530
Asn Arg Pro Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Thr Gly
1535 1540 1545
Arg Thr Phe Leu Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp
1550 1555 1560
Thr Ser Phe Thr Ile Arg Gly Glu Val His Thr Arg Asp Glu Pro
1565 1570 1575
Phe Gln Thr Val His Phe Thr His His Gly Ile Pro Thr Asp Leu
1580 1585 1590
Met Met Val Arg Leu Gly Pro Gly Asn Ser Phe Pro Asn Asn Leu
1595 1600 1605
Asp Lys Phe Gly Leu Asp Gln Met Pro Ala Arg Asn Ser Arg Val
1610 1615 1620
Val Gly Val Ser Ser Ser Tyr Gly Asn Phe Phe Phe Ser Gly Asn
1625 1630 1635
Phe Leu Gly Phe Val Asp Ser Ile Thr Ser Glu Gln Gly Thr Tyr
1640 1645 1650
Ala Arg Leu Phe Arg Tyr Arg Val Thr Thr Tyr Lys Gly Trp Cys
1655 1660 1665
Gly Ser Ala Leu Val Cys Glu Ala Gly Gly Val Arg Arg Ile Ile
1670 1675 1680
Gly Leu His Ser Ala Gly Ala Ala Gly Ile Gly Ala Gly Thr Tyr
1685 1690 1695
Ile Ser Lys Leu Gly Leu Ile Lys Ala Leu Lys His Leu Gly Glu
1700 1705 1710
Pro Leu Ala Thr Met Gln Gly Leu Met Thr Glu Leu Glu Pro Gly
1715 1720 1725
Ile Thr Val His Val Pro Arg Lys Ser Lys Leu Arg Lys Thr Thr
1730 1735 1740
Ala His Ala Val Tyr Lys Pro Glu Phe Glu Pro Ala Val Leu Ser
1745 1750 1755
Lys Phe Asp Pro Arg Leu Asn Lys Asp Val Asp Leu Asp Glu Val
1760 1765 1770
Ile Trp Ser Lys His Thr Ala Asn Val Pro Tyr Gln Pro Pro Leu
1775 1780 1785
Phe Tyr Thr Tyr Met Ser Glu Tyr Ala His Arg Val Phe Ser Phe
1790 1795 1800
Leu Gly Lys Asp Asn Asp Ile Leu Thr Val Lys Glu Ala Ile Leu
1805 1810 1815
Gly Ile Pro Gly Leu Asp Pro Met Asp Pro His Thr Ala Pro Gly
1820 1825 1830
Leu Pro Tyr Ala Ile Asn Gly Leu Arg Arg Thr Asp Leu Val Asp
1835 1840 1845
Phe Val Asn Gly Thr Val Asp Ala Ala Leu Ala Val Gln Ile Gln
1850 1855 1860
Lys Phe Leu Asp Gly Asp Tyr Ser Asp His Val Phe Gln Thr Phe
1865 1870 1875
Leu Lys Asp Glu Ile Arg Pro Ser Glu Lys Val Arg Ala Gly Lys
1880 1885 1890
Thr Arg Ile Val Asp Val Pro Ser Leu Ala His Cys Ile Val Gly
1895 1900 1905
Arg Met Leu Leu Gly Arg Phe Ala Ala Lys Phe Gln Ser His Pro
1910 1915 1920
Gly Phe Leu Leu Gly Ser Ala Ile Gly Ser Asp Pro Asp Val Phe
1925 1930 1935
Trp Thr Val Ile Gly Ala Gln Leu Glu Gly Arg Lys Asn Thr Tyr
1940 1945 1950
Asp Val Asp Tyr Ser Ala Phe Asp Ser Ser His Gly Thr Gly Ser
1955 1960 1965
Phe Glu Ala Leu Ile Ser His Phe Phe Thr Val Asp Asn Gly Phe
1970 1975 1980
Ser Pro Ala Leu Gly Pro Tyr Leu Arg Ser Leu Ala Val Ser Val
1985 1990 1995
His Ala Tyr Gly Glu Arg Arg Ile Lys Ile Thr Gly Gly Leu Pro
2000 2005 2010
Ser Gly Cys Ala Ala Thr Ser Leu Leu Asn Thr Val Leu Asn Asn
2015 2020 2025
Val Ile Ile Arg Thr Ala Leu Ala Leu Thr Tyr Lys Glu Phe Glu
2030 2035 2040
Tyr Asp Met Val Asp Ile Ile Ala Tyr Gly Asp Asp Leu Leu Val
2045 2050 2055
Gly Thr Asp Tyr Asp Leu Asp Phe Asn Glu Val Ala Arg Arg Ala
2060 2065 2070
Ala Lys Leu Gly Tyr Lys Met Thr Pro Ala Asn Lys Gly Ser Val
2075 2080 2085
Phe Pro Pro Thr Ser Ser Leu Ser Asp Ala Val Phe Leu Lys Arg
2090 2095 2100
Lys Phe Val Gln Asn Asn Asp Gly Leu Tyr Lys Pro Val Met Asp
2105 2110 2115
Leu Lys Asn Leu Glu Ala Met Leu Ser Tyr Phe Lys Pro Gly Thr
2120 2125 2130
Leu Leu Glu Lys Leu Gln Ser Val Ser Met Leu Ala Gln His Ser
2135 2140 2145
Gly Lys Glu Glu Tyr Asp Arg Leu Met His Pro Phe Ala Asp Tyr
2150 2155 2160
Gly Ala Val Pro Ser His Glu Tyr Leu Gln Ala Arg Trp Arg Ala
2165 2170 2175
Leu Phe Asp
2180
<210> 17
<211> 2181
<212> PRT
<213> 塞内卡病毒
<400> 17
Met Gln Asn Ser His Phe Ser Phe Asp Thr Ala Ser Gly Thr Phe Glu
1 5 10 15
Asp Val Thr Gly Thr Lys Val Lys Ile Val Glu Tyr Pro Arg Ser Val
20 25 30
Asn Asn Gly Val Tyr Asp Ser Ser Thr His Leu Glu Ile Leu Asn Leu
35 40 45
Gln Gly Glu Ile Glu Ile Leu Arg Ser Phe Asn Glu Tyr Gln Ile Arg
50 55 60
Ala Ala Lys Gln Gln Leu Gly Leu Asp Ile Val Tyr Glu Leu Gln Gly
65 70 75 80
Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly Asn Asn
85 90 95
Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn Ser Val
100 105 110
Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly Asn Ser
115 120 125
Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile Leu Asn
130 135 140
Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu Asn Ser
145 150 155 160
Ala Asp Arg Val Thr Thr Gln Thr Ala Gly Asn Thr Ala Ile Asn Thr
165 170 175
Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro Thr Lys
180 185 190
Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr Phe Thr
195 200 205
Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr Lys Ala
210 215 220
Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala Phe Leu
225 230 235 240
Ser Arg Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr Leu His
245 250 255
Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln Cys Asn
260 265 270
Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val Pro Glu
275 280 285
Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu Gln Glu
290 295 300
Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg Thr Gly
305 310 315 320
Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro Pro Asn
325 330 335
Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr Val Phe
340 345 350
Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp Ile Asn
355 360 365
Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr Gln Asn
370 375 380
Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr Lys Glu
385 390 395 400
Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro Thr Ser
405 410 415
Pro Tyr Phe Asn Gly Leu Arg Asn Arg Tyr Thr Ala Gly Thr Asp Glu
420 425 430
Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu Met Phe
435 440 445
Leu Ser Thr Leu Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn Val Arg
450 455 460
Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu Leu Gln
465 470 475 480
Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Glu Arg Val Pro Glu Pro
485 490 495
Val Pro Ala Ser Asp Thr Tyr Val Pro Tyr Val Ala Val Pro Thr Gln
500 505 510
Phe Asp Asp Arg Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser Asp Pro
515 520 525
Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe Ala Asn
530 535 540
Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro Met Met
545 550 555 560
Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly Thr Gln
565 570 575
Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile Trp Asp
580 585 590
Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Val Pro Tyr Ile Ser Pro
595 600 605
Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr Ser Ala
610 615 620
Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu Pro Pro
625 630 635 640
Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala Gly Glu
645 650 655
Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr Val Phe
660 665 670
His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly Asn Thr
675 680 685
Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn His Thr
690 695 700
Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val Ile Lys
705 710 715 720
Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr Gln Glu
725 730 735
Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro Arg Pro
740 745 750
Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Ala Asn Pro
755 760 765
Ser Gly Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn Phe Tyr
770 775 780
Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val Thr Val
785 790 795 800
Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe Pro Ser
805 810 815
Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu His Val
820 825 830
Pro Phe His Phe Thr Gly Arg Thr Pro Arg Ala Phe Ala Ser Lys Gly
835 840 845
Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser Val Leu
850 855 860
Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr Arg Gly
865 870 875 880
Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Val Pro Arg
885 890 895
Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val Tyr Ile
900 905 910
Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro Phe Arg
915 920 925
Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Ile Glu Thr Asn
930 935 940
Pro Gly Pro Ala Ser Asp Asn Pro Ile Leu Glu Phe Leu Glu Ala Glu
945 950 955 960
Asn Asp Leu Val Thr Leu Ala Ser Leu Trp Lys Met Val His Ser Val
965 970 975
Gln Gln Thr Trp Arg Lys Tyr Val Lys Asn Asp Asp Phe Trp Pro Asn
980 985 990
Leu Leu Ser Glu Leu Val Gly Glu Gly Ser Val Ala Leu Ala Ala Thr
995 1000 1005
Leu Ser Asn Gln Ala Ser Val Lys Ala Leu Leu Gly Leu His Phe
1010 1015 1020
Leu Ser Arg Gly Leu Asn Tyr Thr Asp Phe Tyr Ser Leu Leu Ile
1025 1030 1035
Glu Lys Cys Ser Ser Phe Phe Thr Val Glu Pro Pro Pro Pro Pro
1040 1045 1050
Ala Glu Asn Leu Met Thr Lys Pro Ser Val Lys Ser Lys Phe Arg
1055 1060 1065
Lys Leu Phe Lys Met Gln Gly Pro Met Asp Lys Val Lys Asp Trp
1070 1075 1080
Asn Gln Ile Ala Ala Gly Leu Lys Asn Phe Gln Phe Val Arg Asp
1085 1090 1095
Leu Val Lys Glu Val Val Asp Trp Leu Gln Ala Trp Ile Asn Lys
1100 1105 1110
Glu Lys Ala Ser Pro Val Leu Gln Tyr Gln Leu Glu Met Lys Lys
1115 1120 1125
Leu Gly Pro Val Ala Leu Ala His Asp Ala Phe Met Ala Gly Ser
1130 1135 1140
Gly Pro Pro Leu Ser Asp Asp Gln Ile Glu Tyr Leu Gln Asn Leu
1145 1150 1155
Lys Ser Leu Ala Leu Thr Leu Gly Lys Thr Asn Leu Ala Gln Ser
1160 1165 1170
Leu Thr Thr Met Ile Asn Ala Lys Gln Ser Ser Ala Gln Arg Val
1175 1180 1185
Glu Pro Val Val Val Val Leu Arg Gly Lys Pro Gly Cys Gly Lys
1190 1195 1200
Ser Leu Ala Ser Thr Leu Ile Ala Gln Ala Val Ser Lys Arg Leu
1205 1210 1215
Tyr Gly Ser Gln Ser Val Tyr Ser Leu Pro Pro Asp Pro Asp Phe
1220 1225 1230
Phe Asp Gly Tyr Lys Gly Gln Phe Val Thr Leu Met Asp Asp Leu
1235 1240 1245
Gly Gln Asn Pro Asp Gly Gln Asp Phe Ser Thr Phe Cys Gln Met
1250 1255 1260
Val Ser Thr Ala Gln Phe Leu Pro Asn Met Ala Asp Leu Ala Glu
1265 1270 1275
Lys Gly Arg Pro Phe Thr Ser Asn Leu Ile Ile Ala Thr Thr Asn
1280 1285 1290
Leu Pro His Phe Ser Pro Val Thr Ile Ala Asp Pro Ser Ala Val
1295 1300 1305
Ser Arg Arg Ile Asn Tyr Asp Leu Thr Leu Glu Val Ser Glu Ala
1310 1315 1320
Tyr Lys Lys His Thr Arg Leu Asn Phe Asp Leu Ala Phe Arg Arg
1325 1330 1335
Thr Asp Ala Pro Pro Ile Tyr Pro Phe Ala Ala His Val Pro Phe
1340 1345 1350
Val Asp Val Ala Val Arg Phe Lys Asn Gly His Gln Asn Phe Asn
1355 1360 1365
Leu Leu Glu Leu Val Asp Ser Ile Cys Thr Asp Ile Arg Ala Lys
1370 1375 1380
Gln Gln Gly Ala Arg Asn Met Gln Thr Leu Val Leu Gln Ser Pro
1385 1390 1395
Asn Glu Asn Asp Asp Thr Pro Val Asp Glu Ala Leu Gly Arg Val
1400 1405 1410
Leu Ser Pro Ala Ala Val Asp Glu Ala Leu Val Asp Leu Thr Pro
1415 1420 1425
Glu Ala Asp Pro Val Gly Arg Leu Ala Ile Leu Ala Lys Leu Gly
1430 1435 1440
Leu Ala Leu Ala Ala Val Thr Pro Gly Leu Ile Ile Leu Ala Val
1445 1450 1455
Gly Leu Tyr Arg Tyr Phe Ser Gly Ser Asp Ala Asp Gln Glu Glu
1460 1465 1470
Thr Glu Ser Glu Gly Ser Val Lys Ala Pro Arg Ser Glu Asn Ala
1475 1480 1485
Tyr Asp Gly Pro Lys Lys Asn Ser Lys Pro Pro Gly Ala Leu Ser
1490 1495 1500
Leu Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala
1505 1510 1515
Ala Val Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro
1520 1525 1530
Asn Arg Pro Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Thr Gly
1535 1540 1545
Arg Thr Phe Leu Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp
1550 1555 1560
Thr Ser Phe Thr Ile Arg Gly Glu Val His Thr Arg Asp Glu Pro
1565 1570 1575
Phe Gln Thr Val His Phe Thr His His Gly Ile Pro Thr Asp Leu
1580 1585 1590
Met Met Val Arg Leu Gly Pro Gly Asn Ser Phe Pro Asn Asn Leu
1595 1600 1605
Asp Lys Phe Gly Leu Asp Gln Met Pro Ala Arg Asn Ser Arg Val
1610 1615 1620
Val Gly Val Ser Ser Ser Tyr Gly Asn Phe Phe Phe Ser Gly Asn
1625 1630 1635
Phe Leu Gly Phe Val Asp Ser Ile Thr Ser Glu Gln Gly Thr Tyr
1640 1645 1650
Ala Arg Leu Phe Arg Tyr Arg Val Thr Thr Tyr Lys Gly Trp Cys
1655 1660 1665
Gly Ser Ala Leu Val Cys Glu Ala Gly Gly Val Arg Arg Ile Ile
1670 1675 1680
Gly Leu His Ser Ala Gly Ala Ala Gly Ile Gly Ala Gly Thr Tyr
1685 1690 1695
Ile Ser Lys Leu Gly Leu Ile Lys Ala Leu Lys His Leu Gly Glu
1700 1705 1710
Pro Leu Ala Thr Met Gln Gly Leu Met Thr Glu Leu Glu Pro Gly
1715 1720 1725
Ile Thr Val His Val Pro Arg Lys Ser Lys Leu Arg Lys Thr Thr
1730 1735 1740
Ala His Ala Val Tyr Lys Pro Glu Phe Glu Pro Ala Val Leu Ser
1745 1750 1755
Lys Phe Asp Pro Arg Leu Asn Lys Asp Val Asp Leu Asp Glu Val
1760 1765 1770
Ile Trp Ser Lys His Thr Ala Asn Val Pro Tyr Gln Pro Pro Leu
1775 1780 1785
Phe Tyr Thr Tyr Met Ser Glu Tyr Ala His Arg Val Phe Ser Phe
1790 1795 1800
Leu Gly Lys Asp Asn Asp Ile Leu Thr Val Lys Glu Ala Ile Leu
1805 1810 1815
Gly Ile Pro Gly Leu Asp Pro Met Asp Pro His Thr Ala Pro Gly
1820 1825 1830
Leu Pro Tyr Ala Ile Asn Gly Leu Arg Arg Thr Asp Leu Val Asp
1835 1840 1845
Phe Val Asn Gly Thr Val Asp Ala Ala Leu Ala Val Gln Ile Gln
1850 1855 1860
Lys Phe Leu Asp Gly Asp Tyr Ser Asp His Val Phe Gln Thr Phe
1865 1870 1875
Leu Lys Asp Glu Ile Arg Pro Ser Glu Lys Val Arg Ala Gly Lys
1880 1885 1890
Thr Arg Ile Val Asp Val Pro Ser Leu Ala His Cys Ile Val Gly
1895 1900 1905
Arg Met Leu Leu Gly Arg Phe Ala Ala Lys Phe Gln Ser His Pro
1910 1915 1920
Gly Phe Leu Leu Gly Ser Ala Ile Gly Ser Asp Pro Asp Val Phe
1925 1930 1935
Trp Thr Val Ile Gly Ala Gln Leu Glu Gly Arg Lys Asn Thr Tyr
1940 1945 1950
Asp Val Asp Tyr Ser Ala Phe Asp Ser Ser His Gly Thr Gly Ser
1955 1960 1965
Phe Glu Ala Leu Ile Ser His Phe Phe Thr Val Asp Asn Gly Phe
1970 1975 1980
Ser Pro Ala Leu Gly Pro Tyr Leu Arg Ser Leu Ala Val Ser Val
1985 1990 1995
His Ala Tyr Gly Glu Arg Arg Ile Lys Ile Thr Gly Gly Leu Pro
2000 2005 2010
Ser Gly Cys Ala Ala Thr Ser Leu Leu Asn Thr Val Leu Asn Asn
2015 2020 2025
Val Ile Ile Arg Thr Ala Leu Ala Leu Thr Tyr Lys Glu Phe Glu
2030 2035 2040
Tyr Asp Met Val Asp Ile Ile Ala Tyr Gly Asp Asp Leu Leu Val
2045 2050 2055
Gly Thr Asp Tyr Asp Leu Asp Phe Asn Glu Val Ala Arg Arg Ala
2060 2065 2070
Ala Lys Leu Gly Tyr Lys Met Thr Pro Ala Asn Lys Gly Ser Val
2075 2080 2085
Phe Pro Pro Thr Ser Ser Leu Ser Asp Ala Val Phe Leu Lys Arg
2090 2095 2100
Lys Phe Val Gln Asn Asn Asp Gly Leu Tyr Lys Pro Val Met Asp
2105 2110 2115
Leu Lys Asn Leu Glu Ala Met Leu Ser Tyr Phe Lys Pro Gly Thr
2120 2125 2130
Leu Leu Glu Lys Leu Gln Ser Val Ser Met Leu Ala Gln His Ser
2135 2140 2145
Gly Lys Glu Glu Tyr Asp Arg Leu Met His Pro Phe Ala Asp Tyr
2150 2155 2160
Gly Ala Val Pro Ser His Glu Tyr Leu Gln Ala Arg Trp Arg Ala
2165 2170 2175
Leu Phe Asp
2180
<210> 18
<211> 3308
<212> DNA
<213> 塞内卡病毒
<400> 18
ggatccgcca ccatgggtaa tgttcagaca acctcaaaga atgattttga ttcccgcggc 60
aataatggta acatgacctt caattactac gcaaacactt accagaattc agtagacttc 120
tcgacctcct cgtcggcgtc aggcgccgga cccgggaact cccggggcgg actagcgggt 180
ctcctcacaa atttcagtgg aatcttgaac cctcttggct acctcaaaga tcacaatacc 240
gaagaaatgg aaaactctgc tgatcgagtc ataacgcaaa cggcgggcaa cactgccata 300
aacacgcaat catcactggg tgtgttgtgt gcctacgttg aagacccgac caaatctgac 360
cctccgtcca gcagcacaga tcaacccacc accactttta ctgccatcga caggtggtac 420
actggacgcc tcaattcttg gacaaaagct gtaaaaacct tctcttttca ggccgtcccg 480
ctccctggag ccttcctgtc taaacaggga ggcctcaacg gaggggcctt cacggctacc 540
ctacatagac atttcttaat gaagtgcggg tggcaggtgc aggtccaatg caatttgacg 600
caattccacc aaggtgctct tcttgttgcc atggtccccg aaaccaccct tgatgtcaaa 660
cctgacggca aggcaaagag cttacaggag ctgaatgaag agcagtgggt ggaaatgtct 720
gacgattacc ggaccgggaa aaacatgcct tttcagtctc ttggcacata ctatcggccc 780
cctaactgga cttggggccc caatttcatc aacccctatc aagtaacagt tttcccacac 840
caaattctga acgcgagaac ctctacctcg gtagacataa gtgtcccata catcggggag 900
actcctacac aatcctcaga gacacagaac tcctggaccc tccttgttat ggtgcttgtc 960
cccctggact acaaggaggg agccacaact gacccagaaa ttacattttc tgtaaggcct 1020
acaagtccct acttcaatgg gcttcgtaac cgtttcacga ccgggacgga cgaggaacag 1080
gggcccattc ccacagcacc cagagaaaat tcgcttatgt ttctctcaac catccctgac 1140
gacactgtcc ctgcttacgg gaatgtgcgt acccctcccg tcaattacct ccccggtgaa 1200
ataaccgacc tcttacaact ggcccgtata cccactctca tggcgtttgg gcgggtgtct 1260
gaacccgagc ctgcctcaga cgcatatgtg ccctacgttg ccgttcctgc ccagttcgac 1320
gacaagcctc tcatctcctt cccgatcacc ctttcagatc ctgtctacca gaacaccctg 1380
gtaggcgcca tcagttcgaa cttcgccaac taccgggggt gtatccaaat cactctgaca 1440
ttttgtggac ccatgatggc aagagggaaa ttcctgctct cgtattctcc cccaaatgga 1500
gcacaaccac agaccctttc tgaagctatg cagtgcacat actctatttg ggatataggc 1560
ttgaactcta gttggacctt tgtcatcccc tacatctcgc ccagtgatta ccgtgaaact 1620
cgggctatta ccaactcagt ttattctgct gatggttggt ttagcttgca caagctgacc 1680
aaaattactc taccacctga ctgcccacag agtccctgta ttctcttttt cgcctctgct 1740
ggtgaggatt acaccctccg tctccctgtt gattgtaatc cttcctacgt gttccactcc 1800
accgacaacg ccgagactgg ggttattgag gcaggtaaca ctgacaccga tttctctggt 1860
gaactggcgg ctcctggctc taaccatact aatgtcaaat tcctgtttga ccgatctcga 1920
ctactgaatg taattaaggt actggagaag gacgccgtct tcccccgtcc tttccccaca 1980
gcaacaggtg cacagcagga cgatggttac ttttgtcttc taacaccccg cccaacagtc 2040
gcttcccgac ccgccactcg tttcggcctg tacgtcaacc cgtctgacag tggcgttctc 2100
gctaacactt cactggattt caatttttac agtttggcct gtttcactta ctttagatca 2160
gaccttgaag tcacggtggt ctcactggag ccagatttgg aattcgccgt ggggtggttc 2220
ccctctggca gtgagtacca ggcttctagc tttgtctacg accaactgca tgtaccctac 2280
cactttactg ggcgcactcc ccgcgctttc accagcaagg gtggaaaggt atctttcgtg 2340
ctcccttgga actctgtctc ttccgtgctt cccgtgcgct gggggggcgc ttccaagctt 2400
tcttctgcca cgcggggtct gccggctcat gctgactggg ggaccattta cgcctttatc 2460
ccccgtccta acgagaagaa aagcaccgct gtaaagcacg tggcggtgta cgttcggtac 2520
aagaacgcgc gtgcttggtg ccccagcatg cttccctttc gcagctacaa gcaaaagatg 2580
ctgatgcaat caggcgacat cgagaccaac cctggccctg gttcaggtaa gccccctgga 2640
gcgctctctc ttatggaaat gcaacagccc aacgtggaca tgggctttga ggctgcggtc 2700
gctaagaaag tggtcgtccc cattaccttc atggttccca acagaccttc tggacttaca 2760
cagtccgctc ttcttgtggc cggccggacc ttcctaatca atgagcatac atggtccaac 2820
ccctcctgga ccagcttcac aatccgtggt gaggtgcaca ctcgtgatga gcctttccaa 2880
acggttcatt ttactcacca tggtcttccc acagatctga tgatggtacg tctcggaccg 2940
ggcaactctt tccctaacaa tctagacaag tttggacttg accagatgcc ggcacgtaac 3000
tcccgtgtgg ttggcgtttc ggctagttac ggtaacttct tcttctctgg gaacttcctc 3060
gggtttgttg actccatcac ctctgaccaa ggaacctatg cgagactttt caggtacagg 3120
gtgacgactt acaagggatg gtgcggttcg gccctggtct gtgaggccgg tggtgtccga 3180
cgcatcattg gcatgcattc tgctggtgcc gctggtatcg gcgccgggac ttacatctca 3240
aaattaggac tgatcaaagc ccttaaacac ctcggtgagc ctctggctac aatgcaatga 3300
gcggccgc 3308
<210> 19
<211> 1095
<212> PRT
<213> 塞内卡病毒
<400> 19
Met Gly Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly
1 5 10 15
Asn Asn Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn
20 25 30
Ser Val Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly
35 40 45
Asn Ser Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile
50 55 60
Leu Asn Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu
65 70 75 80
Asn Ser Ala Asp Arg Val Ile Thr Gln Thr Ala Gly Asn Thr Ala Ile
85 90 95
Asn Thr Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro
100 105 110
Thr Lys Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr
115 120 125
Phe Thr Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr
130 135 140
Lys Ala Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala
145 150 155 160
Phe Leu Ser Lys Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr
165 170 175
Leu His Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln
180 185 190
Cys Asn Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val
195 200 205
Pro Glu Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu
210 215 220
Gln Glu Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg
225 230 235 240
Thr Gly Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro
245 250 255
Pro Asn Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr
260 265 270
Val Phe Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp
275 280 285
Ile Ser Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr
290 295 300
Gln Asn Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr
305 310 315 320
Lys Glu Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro
325 330 335
Thr Ser Pro Tyr Phe Asn Gly Leu Arg Asn Arg Phe Thr Thr Gly Thr
340 345 350
Asp Glu Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu
355 360 365
Met Phe Leu Ser Thr Ile Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn
370 375 380
Val Arg Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu
385 390 395 400
Leu Gln Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Gly Arg Val Ser
405 410 415
Glu Pro Glu Pro Ala Ser Asp Ala Tyr Val Pro Tyr Val Ala Val Pro
420 425 430
Ala Gln Phe Asp Asp Lys Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser
435 440 445
Asp Pro Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe
450 455 460
Ala Asn Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro
465 470 475 480
Met Met Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly
485 490 495
Ala Gln Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile
500 505 510
Trp Asp Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Ile Pro Tyr Ile
515 520 525
Ser Pro Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr
530 535 540
Ser Ala Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu
545 550 555 560
Pro Pro Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala
565 570 575
Gly Glu Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr
580 585 590
Val Phe His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly
595 600 605
Asn Thr Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn
610 615 620
His Thr Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val
625 630 635 640
Ile Lys Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr
645 650 655
Ala Thr Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro
660 665 670
Arg Pro Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Val
675 680 685
Asn Pro Ser Asp Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn
690 695 700
Phe Tyr Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val
705 710 715 720
Thr Val Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe
725 730 735
Pro Ser Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu
740 745 750
His Val Pro Tyr His Phe Thr Gly Arg Thr Pro Arg Ala Phe Thr Ser
755 760 765
Lys Gly Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser
770 775 780
Val Leu Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr
785 790 795 800
Arg Gly Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Ile
805 810 815
Pro Arg Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val
820 825 830
Tyr Val Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro
835 840 845
Phe Arg Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Ile Glu
850 855 860
Thr Asn Pro Gly Pro Gly Ser Gly Lys Pro Pro Gly Ala Leu Ser Leu
865 870 875 880
Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala Ala Val
885 890 895
Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro Asn Arg Pro
900 905 910
Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Ala Gly Arg Thr Phe Leu
915 920 925
Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp Thr Ser Phe Thr Ile
930 935 940
Arg Gly Glu Val His Thr Arg Asp Glu Pro Phe Gln Thr Val His Phe
945 950 955 960
Thr His His Gly Leu Pro Thr Asp Leu Met Met Val Arg Leu Gly Pro
965 970 975
Gly Asn Ser Phe Pro Asn Asn Leu Asp Lys Phe Gly Leu Asp Gln Met
980 985 990
Pro Ala Arg Asn Ser Arg Val Val Gly Val Ser Ala Ser Tyr Gly Asn
995 1000 1005
Phe Phe Phe Ser Gly Asn Phe Leu Gly Phe Val Asp Ser Ile Thr
1010 1015 1020
Ser Asp Gln Gly Thr Tyr Ala Arg Leu Phe Arg Tyr Arg Val Thr
1025 1030 1035
Thr Tyr Lys Gly Trp Cys Gly Ser Ala Leu Val Cys Glu Ala Gly
1040 1045 1050
Gly Val Arg Arg Ile Ile Gly Met His Ser Ala Gly Ala Ala Gly
1055 1060 1065
Ile Gly Ala Gly Thr Tyr Ile Ser Lys Leu Gly Leu Ile Lys Ala
1070 1075 1080
Leu Lys His Leu Gly Glu Pro Leu Ala Thr Met Gln
1085 1090 1095
<210> 20
<211> 3308
<212> DNA
<213> 塞内卡病毒
<400> 20
ggatccgcca ccatgggcaa cgttcaaact acctccaaga atgattttga ctcccgcggc 60
aacaacggca acatgacttt taactactac gccaatacgt atcaaaactc tgttgatttc 120
tcgacatcga gttccgcttc cggcgcggga cctggaaatt cccgcggtgg actggccggt 180
ctgctcacaa acttttccgg tatcctgaac cccctcggtt atctgaaaga tcacaatacg 240
gaagagatgg agaactctgc cgatcgtgtg attacgcaga cagctggtaa cacggctatc 300
aacactcaat cgtctctggg agtactctgt gcttacgtcg aggacccaac aaaatccgac 360
cctccatctt cctcgaccga tcaacctacg actaccttca cggccataga caggtggtat 420
acaggtcgcc tgaattcgtg gacaaaggct gttaaaacct ttagcttcca ggctgtgcca 480
ttgcccggtg ctttcctttc ccgccagggc ggcctcaacg gtggagcttt tactgctaca 540
ctgcacagac actttctgat gaaatgcggt tggcaggtgc aggtacagtg caatttgact 600
caattccacc aaggtgcact tctcgttgct atggttcccg agactacgct tgacgttaag 660
cctgacggca aggccaagtc tctccaagag ctgaatgagg aacagtgggt tgagatgagc 720
gatgactata gaaccggtaa aaacatgcca ttccagtccc tgggcacata ctacagaccc 780
ccaaattgga cttggggccc gaactttatc aatccgtatc aggtcaccgt gtttccacac 840
caaatcctga atgccaggac tagtaccagc gtcgatatta gcgtgcccta tatcggcgaa 900
acgccaaccc aatcctccga aactcagaac agctggacgc ttctggtaat ggtgttggta 960
cccttggatt ataaggaggg agccactacc gaccctgaaa tcactttttc ggtaaggccc 1020
actagccctt acttcaacgg actgcgcaac cgtttcacca ccggcactga tgaggagcaa 1080
ggccctatcc ctactgcccc cagagaaaat agcctgatgt ttctgagcac aattcctgac 1140
gacaccgtac ctgcctatgg taacgttcgt acgcctcccg taaactacct gcctggtgaa 1200
attacggacc tcttgcagct ggcccgcatc cctacactga tggccttcgg tcgtgtcagt 1260
gagcccgaac cagccagcga cgcttacgtt ccatatgttg cggtacctgc tcagttcgac 1320
gacaagccgt tgataagttt cccaatcact ttgagcgacc ctgtatacca gaacactttg 1380
gttggagcta tctcctcgaa ctttgcgaac taccgtggtt gtattcaaat cacccttaca 1440
ttctgcggcc cgatgatggc tcgtggcaag ttcctgttga gctactcccc ccccaacgga 1500
gcacaaccac agacactgtc cgaggccatg cagtgcacat actccatctg ggatatcggt 1560
ctcaacagct catggacctt tgtaatacca tacatctcgc catccgatta tagagagacc 1620
cgcgccatca ccaacagtgt gtactcagcc gatggatggt tcagtctcca taagcttaca 1680
aagatcactc tgccccccga ctgcccacaa tcaccctgca tattgttctt tgcctcagct 1740
ggtgaagatt acacgcttcg tttgcccgtc gactgtaacc cgtcttacgt gttccactcc 1800
acggacaatg ctgagaccgg tgtaattgag gctggtaaca ccgacacgga tttctctggt 1860
gagctggcgg ctcccggttc taaccatacc aacgtgaagt tccttttcga ccgttcacgt 1920
cttttgaacg taatcaaggt cttggaaaag gacgctgtgt tccctcgccc attccccaca 1980
gcaacgggag cacaacaaga cgacggctat ttctgcctgc tgacaccacg tcctactgtg 2040
gctagccgtc cggccacacg ctttggtctc tacgttaacc ctagcgactc tggtgtactg 2100
gctaacacct ccctggactt caatttctac tctctggcct gcttcacgta cttcaggagc 2160
gacctggagg tcactgtggt gtctctggaa ccagatctgg aatttgcggt aggatggttc 2220
ccttcaggaa gcgagtacca ggcatcgtcc tttgtgtacg accaacttca tgttccctac 2280
catttcaccg gtagaacccc acgtgccttc accagtaagg gaggcaaagt ttcttttgta 2340
ctgccctgga attctgtcag ttccgttctc ccggtccgct ggggcggagc gtcaaagctc 2400
tcatccgcga cccgcggatt gcccgcacac gcggattggg gaactatcta cgctttcatt 2460
ccacgcccta atgaaaagaa gtctacagca gtgaagcacg tggccgtcta tgtgcgttac 2520
aagaatgcaa gggcgtggtg tccgtctatg ttgccattcc gtagctataa acagaagatg 2580
cttatgcaaa gcggtgatat tgagacgaat cctggacctg gttcaggtaa gccccctgga 2640
gcgctctctc ttatggaaat gcaacagccc aacgtggaca tgggctttga ggctgcggtc 2700
gctaagaaag tggtcgtccc cattaccttc atggttccca acagaccttc tggacttaca 2760
cagtccgctc ttcttgtggc cggccggacc ttcctaatca atgagcatac atggtccaac 2820
ccctcctgga ccagcttcac aatccgtggt gaggtgcaca ctcgtgatga gcctttccaa 2880
acggttcatt ttactcacca tggtcttccc acagatctga tgatggtacg tctcggaccg 2940
ggcaactctt tccctaacaa tctagacaag tttggacttg accagatgcc ggcacgtaac 3000
tcccgtgtgg ttggcgtttc ggctagttac ggtaacttct tcttctctgg gaacttcctc 3060
gggtttgttg actccatcac ctctgaccaa ggaacctatg cgagactttt caggtacagg 3120
gtgacgactt acaagggatg gtgcggttcg gccctggtct gtgaggccgg tggtgtccga 3180
cgcatcattg gcatgcattc tgctggtgcc gctggtatcg gcgccgggac ttacatctca 3240
aaattaggac tgatcaaagc ccttaaacac ctcggtgagc ctctggctac aatgcaatga 3300
gcggccgc 3308
<210> 21
<211> 1095
<212> PRT
<213> 塞内卡病毒
<400> 21
Met Gly Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly
1 5 10 15
Asn Asn Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn
20 25 30
Ser Val Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly
35 40 45
Asn Ser Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile
50 55 60
Leu Asn Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu
65 70 75 80
Asn Ser Ala Asp Arg Val Ile Thr Gln Thr Ala Gly Asn Thr Ala Ile
85 90 95
Asn Thr Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro
100 105 110
Thr Lys Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr
115 120 125
Phe Thr Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr
130 135 140
Lys Ala Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala
145 150 155 160
Phe Leu Ser Arg Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr
165 170 175
Leu His Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln
180 185 190
Cys Asn Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val
195 200 205
Pro Glu Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu
210 215 220
Gln Glu Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg
225 230 235 240
Thr Gly Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro
245 250 255
Pro Asn Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr
260 265 270
Val Phe Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp
275 280 285
Ile Ser Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr
290 295 300
Gln Asn Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr
305 310 315 320
Lys Glu Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro
325 330 335
Thr Ser Pro Tyr Phe Asn Gly Leu Arg Asn Arg Phe Thr Thr Gly Thr
340 345 350
Asp Glu Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu
355 360 365
Met Phe Leu Ser Thr Ile Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn
370 375 380
Val Arg Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu
385 390 395 400
Leu Gln Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Gly Arg Val Ser
405 410 415
Glu Pro Glu Pro Ala Ser Asp Ala Tyr Val Pro Tyr Val Ala Val Pro
420 425 430
Ala Gln Phe Asp Asp Lys Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser
435 440 445
Asp Pro Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe
450 455 460
Ala Asn Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro
465 470 475 480
Met Met Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly
485 490 495
Ala Gln Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile
500 505 510
Trp Asp Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Ile Pro Tyr Ile
515 520 525
Ser Pro Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr
530 535 540
Ser Ala Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu
545 550 555 560
Pro Pro Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala
565 570 575
Gly Glu Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr
580 585 590
Val Phe His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly
595 600 605
Asn Thr Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn
610 615 620
His Thr Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val
625 630 635 640
Ile Lys Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr
645 650 655
Ala Thr Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro
660 665 670
Arg Pro Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Val
675 680 685
Asn Pro Ser Asp Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn
690 695 700
Phe Tyr Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val
705 710 715 720
Thr Val Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe
725 730 735
Pro Ser Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu
740 745 750
His Val Pro Tyr His Phe Thr Gly Arg Thr Pro Arg Ala Phe Thr Ser
755 760 765
Lys Gly Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser
770 775 780
Val Leu Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr
785 790 795 800
Arg Gly Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Ile
805 810 815
Pro Arg Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val
820 825 830
Tyr Val Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro
835 840 845
Phe Arg Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Ile Glu
850 855 860
Thr Asn Pro Gly Pro Gly Ser Gly Lys Pro Pro Gly Ala Leu Ser Leu
865 870 875 880
Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala Ala Val
885 890 895
Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro Asn Arg Pro
900 905 910
Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Ala Gly Arg Thr Phe Leu
915 920 925
Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp Thr Ser Phe Thr Ile
930 935 940
Arg Gly Glu Val His Thr Arg Asp Glu Pro Phe Gln Thr Val His Phe
945 950 955 960
Thr His His Gly Leu Pro Thr Asp Leu Met Met Val Arg Leu Gly Pro
965 970 975
Gly Asn Ser Phe Pro Asn Asn Leu Asp Lys Phe Gly Leu Asp Gln Met
980 985 990
Pro Ala Arg Asn Ser Arg Val Val Gly Val Ser Ala Ser Tyr Gly Asn
995 1000 1005
Phe Phe Phe Ser Gly Asn Phe Leu Gly Phe Val Asp Ser Ile Thr
1010 1015 1020
Ser Asp Gln Gly Thr Tyr Ala Arg Leu Phe Arg Tyr Arg Val Thr
1025 1030 1035
Thr Tyr Lys Gly Trp Cys Gly Ser Ala Leu Val Cys Glu Ala Gly
1040 1045 1050
Gly Val Arg Arg Ile Ile Gly Met His Ser Ala Gly Ala Ala Gly
1055 1060 1065
Ile Gly Ala Gly Thr Tyr Ile Ser Lys Leu Gly Leu Ile Lys Ala
1070 1075 1080
Leu Lys His Leu Gly Glu Pro Leu Ala Thr Met Gln
1085 1090 1095
<210> 22
<211> 3308
<212> DNA
<213> 塞内卡病毒
<400> 22
ggatccgcca ccatgggtaa tgttcagaca acctcaaaga atgattttga ttcccgcggc 60
aataatggta acatgacctt caattactac gcaaacactt accagaattc agtagacttc 120
tcgacctcct cgtcggcgtc aggcgccgga cccgggaact cccggggcgg actagcgggt 180
ctcctcacaa atttcagtgg aatcttgaac cctcttggct acctcaaaga tcacaatacc 240
gaagaaatgg aaaactctgc tgatcgagtc ataacgcaaa cggcgggcaa cactgccata 300
aacacgcaat catcactggg tgtgttgtgt gcctacgttg aagacccgac caaatctgac 360
cctccgtcca gcagcacaga tcaacccacc accactttta ctgccatcga caggtggtac 420
actggacgcc tcaattcttg gacaaaagct gtaaaaacct tctcttttca ggccgtcccg 480
ctccctggag ccttcctgtc taaacaggga ggcctcaacg gaggggcctt cacggctacc 540
ctacatagac atttcttaat gaagtgcggg tggcaggtgc aggtccaatg caatttgacg 600
caattccacc aaggtgctct tcttgttgcc atggtccccg aaaccaccct tgatgtcaaa 660
cctgacggca aggcaaagag cttacaggag ctgaatgaag agcagtgggt ggaaatgtct 720
gacgattacc ggaccgggaa aaacatgcct tttcagtctc ttggcacata ctatcggccc 780
cctaactgga cttggggccc caatttcatc aacccctatc aagtaacagt tttcccacac 840
caaattctga acgcgagaac ctctacctcg gtagacataa gtgtcccata catcggggag 900
actcctacac aatcctcaga gacacagaac tcctggaccc tccttgttat ggtgcttgtc 960
cccctggact acaaggaggg agccacaact gacccagaaa ttacattttc tgtaaggcct 1020
acaagtccct acttcaatgg gcttcgtaac cgtttcacga ccgggacgga cgaggaacag 1080
gggcccattc ccacagcacc cagagaaaat tcgcttatgt ttctctcaac catccctgac 1140
gacactgtcc ctgcttacgg gaatgtgcgt acccctcccg tcaattacct ccccggtgaa 1200
ataaccgacc tcttacaact ggcccgtata cccactctca tggcgtttgg gcgggtgtct 1260
gaacccgagc ctgcctcaga cgcatatgtg ccctacgttg ccgttcctgc ccagttcgac 1320
gacaagcctc tcatctcctt cccgatcacc ctttcagatc ctgtctacca gaacaccctg 1380
gtaggcgcca tcagttcgaa cttcgccaac taccgggggt gtatccaaat cactctgaca 1440
ttttgtggac ccatgatggc aagagggaaa ttcctgctct cgtattctcc cccaaatgga 1500
gcacaaccac agaccctttc tgaagctatg cagtgcacat actctatttg ggatataggc 1560
ttgaactcta gttggacctt tgtcatcccc tacatctcgc ccagtgatta ccgtgaaact 1620
cgggctatta ccaactcagt ttattctgct gatggttggt ttagcttgca caagctgacc 1680
aaaattactc taccacctga ctgcccacag agtccctgta ttctcttttt cgcctctgct 1740
ggtgaggatt acaccctccg tctccctgtt gattgtaatc cttcctacgt gcctcagggg 1800
gttgacaacg ccgagactgg ggttattgag gcaggtaaca ctgacaccga tttctctggt 1860
gaactggcgg ctcctggctc taaccatact aatgtcaaat tcctgtttga ccgatctcga 1920
ctactgaatg taattaaggt actggagaag gacgccgtct tcccccgtcc tttccccaca 1980
gcaacaggtg cacagcagga cgatggttac ttttgtcttc taacaccccg cccaacagtc 2040
gcttcccgac ccgccactcg tttcggcctg tacgtcaacc cgtctgacag tggcgttctc 2100
gctaacactt cactggattt caatttttac agtttggcct gtttcactta ctttagatca 2160
gaccttgaag tcacggtggt ctcactggag ccagatttgg aattcgccgt ggggtggttc 2220
ccctctggca gtgagtacca ggcttctagc tttgtctacg accaactgca tgtaccctac 2280
cactttactg ggcgcactcc ccgcgctttc accagcaagg gtggaaaggt atctttcgtg 2340
ctcccttgga actctgtctc ttccgtgctt cccgtgcgct gggggggcgc ttccaagctt 2400
tcttctgcca cgcggggtct gccggctcat gctgactggg ggaccattta cgcctttatc 2460
ccccgtccta acgagaagaa aagcaccgct gtaaagcacg tggcggtgta cgttcggtac 2520
aagaacgcgc gtgcttggtg ccccagcatg cttccctttc gcagctacaa gcaaaagatg 2580
ctgatgcaat caggcgacat cgagaccaac cctggccctg gttcaggtaa gccccctgga 2640
gcgctctctc ttatggaaat gcaacagccc aacgtggaca tgggctttga ggctgcggtc 2700
gctaagaaag tggtcgtccc cattaccttc atggttccca acagaccttc tggacttaca 2760
cagtccgctc ttcttgtggc cggccggacc ttcctaatca atgagcatac atggtccaac 2820
ccctcctgga ccagcttcac aatccgtggt gaggtgcaca ctcgtgatga gcctttccaa 2880
acggttcatt ttactcacca tggtcttccc acagatctga tgatggtacg tctcggaccg 2940
ggcaactctt tccctaacaa tctagacaag tttggacttg accagatgcc ggcacgtaac 3000
tcccgtgtgg ttggcgtttc ggctagttac ggtaacttct tcttctctgg gaacttcctc 3060
gggtttgttg actccatcac ctctgaccaa ggaacctatg cgagactttt caggtacagg 3120
gtgacgactt acaagggatg gtgcggttcg gccctggtct gtgaggccgg tggtgtccga 3180
cgcatcattg gcatgcattc tgctggtgcc gctggtatcg gcgccgggac ttacatctca 3240
aaattaggac tgatcaaagc ccttaaacac ctcggtgagc ctctggctac aatgcaatga 3300
gcggccgc 3308
<210> 23
<211> 1095
<212> PRT
<213> 塞内卡病毒
<400> 23
Met Gly Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly
1 5 10 15
Asn Asn Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn
20 25 30
Ser Val Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly
35 40 45
Asn Ser Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile
50 55 60
Leu Asn Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu
65 70 75 80
Asn Ser Ala Asp Arg Val Ile Thr Gln Thr Ala Gly Asn Thr Ala Ile
85 90 95
Asn Thr Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro
100 105 110
Thr Lys Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr
115 120 125
Phe Thr Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr
130 135 140
Lys Ala Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala
145 150 155 160
Phe Leu Ser Lys Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr
165 170 175
Leu His Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln
180 185 190
Cys Asn Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val
195 200 205
Pro Glu Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu
210 215 220
Gln Glu Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg
225 230 235 240
Thr Gly Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro
245 250 255
Pro Asn Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr
260 265 270
Val Phe Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp
275 280 285
Ile Ser Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr
290 295 300
Gln Asn Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr
305 310 315 320
Lys Glu Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro
325 330 335
Thr Ser Pro Tyr Phe Asn Gly Leu Arg Asn Arg Phe Thr Thr Gly Thr
340 345 350
Asp Glu Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu
355 360 365
Met Phe Leu Ser Thr Ile Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn
370 375 380
Val Arg Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu
385 390 395 400
Leu Gln Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Gly Arg Val Ser
405 410 415
Glu Pro Glu Pro Ala Ser Asp Ala Tyr Val Pro Tyr Val Ala Val Pro
420 425 430
Ala Gln Phe Asp Asp Lys Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser
435 440 445
Asp Pro Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe
450 455 460
Ala Asn Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro
465 470 475 480
Met Met Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly
485 490 495
Ala Gln Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile
500 505 510
Trp Asp Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Ile Pro Tyr Ile
515 520 525
Ser Pro Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr
530 535 540
Ser Ala Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu
545 550 555 560
Pro Pro Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala
565 570 575
Gly Glu Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr
580 585 590
Val Pro Gln Gly Val Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly
595 600 605
Asn Thr Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn
610 615 620
His Thr Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val
625 630 635 640
Ile Lys Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr
645 650 655
Ala Thr Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro
660 665 670
Arg Pro Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Val
675 680 685
Asn Pro Ser Asp Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn
690 695 700
Phe Tyr Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val
705 710 715 720
Thr Val Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe
725 730 735
Pro Ser Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu
740 745 750
His Val Pro Tyr His Phe Thr Gly Arg Thr Pro Arg Ala Phe Thr Ser
755 760 765
Lys Gly Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser
770 775 780
Val Leu Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr
785 790 795 800
Arg Gly Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Ile
805 810 815
Pro Arg Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val
820 825 830
Tyr Val Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro
835 840 845
Phe Arg Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Ile Glu
850 855 860
Thr Asn Pro Gly Pro Gly Ser Gly Lys Pro Pro Gly Ala Leu Ser Leu
865 870 875 880
Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala Ala Val
885 890 895
Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro Asn Arg Pro
900 905 910
Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Ala Gly Arg Thr Phe Leu
915 920 925
Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp Thr Ser Phe Thr Ile
930 935 940
Arg Gly Glu Val His Thr Arg Asp Glu Pro Phe Gln Thr Val His Phe
945 950 955 960
Thr His His Gly Leu Pro Thr Asp Leu Met Met Val Arg Leu Gly Pro
965 970 975
Gly Asn Ser Phe Pro Asn Asn Leu Asp Lys Phe Gly Leu Asp Gln Met
980 985 990
Pro Ala Arg Asn Ser Arg Val Val Gly Val Ser Ala Ser Tyr Gly Asn
995 1000 1005
Phe Phe Phe Ser Gly Asn Phe Leu Gly Phe Val Asp Ser Ile Thr
1010 1015 1020
Ser Asp Gln Gly Thr Tyr Ala Arg Leu Phe Arg Tyr Arg Val Thr
1025 1030 1035
Thr Tyr Lys Gly Trp Cys Gly Ser Ala Leu Val Cys Glu Ala Gly
1040 1045 1050
Gly Val Arg Arg Ile Ile Gly Met His Ser Ala Gly Ala Ala Gly
1055 1060 1065
Ile Gly Ala Gly Thr Tyr Ile Ser Lys Leu Gly Leu Ile Lys Ala
1070 1075 1080
Leu Lys His Leu Gly Glu Pro Leu Ala Thr Met Gln
1085 1090 1095
<210> 24
<211> 4694
<212> DNA
<213> 塞内卡病毒
<400> 24
ggatccgcca ccatgggtaa tgttcagaca acctcaaaga atgattttga ttcccgcggc 60
aataatggta acatgacctt caattactac gcaaacactt accagaattc agtagacttc 120
tcgacctcct cgtcggcgtc aggcgccgga cccgggaact cccggggcgg actagcgggt 180
ctcctcacaa atttcagtgg aatcttgaac cctcttggct acctcaaaga tcacaatacc 240
gaagaaatgg aaaactctgc tgatcgagtc ataacgcaaa cggcgggcaa cactgccata 300
aacacgcaat catcactggg tgtgttgtgt gcctacgttg aagacccgac caaatctgac 360
cctccgtcca gcagcacaga tcaacccacc accactttta ctgccatcga caggtggtac 420
actggacgcc tcaattcttg gacaaaagct gtaaaaacct tctcttttca ggccgtcccg 480
ctccctggag ccttcctgtc taaacaggga ggcctcaacg gaggggcctt cacggctacc 540
ctacatagac atttcttaat gaagtgcggg tggcaggtgc aggtccaatg caatttgacg 600
caattccacc aaggtgctct tcttgttgcc atggtccccg aaaccaccct tgatgtcaaa 660
cctgacggca aggcaaagag cttacaggag ctgaatgaag agcagtgggt ggaaatgtct 720
gacgattacc ggaccgggaa aaacatgcct tttcagtctc ttggcacata ctatcggccc 780
cctaactgga cttggggccc caatttcatc aacccctatc aagtaacagt tttcccacac 840
caaattctga acgcgagaac ctctacctcg gtagacataa gtgtcccata catcggggag 900
actcctacac aatcctcaga gacacagaac tcctggaccc tccttgttat ggtgcttgtc 960
cccctggact acaaggaggg agccacaact gacccagaaa ttacattttc tgtaaggcct 1020
acaagtccct acttcaatgg gcttcgtaac cgtttcacga ccgggacgga cgaggaacag 1080
gggcccattc ccacagcacc cagagaaaat tcgcttatgt ttctctcaac catccctgac 1140
gacactgtcc ctgcttacgg gaatgtgcgt acccctcccg tcaattacct ccccggtgaa 1200
ataaccgacc tcttacaact ggcccgtata cccactctca tggcgtttgg gcgggtgtct 1260
gaacccgagc ctgcctcaga cgcatatgtg ccctacgttg ccgttcctgc ccagttcgac 1320
gacaagcctc tcatctcctt cccgatcacc ctttcagatc ctgtctacca gaacaccctg 1380
gtaggcgcca tcagttcgaa cttcgccaac taccgggggt gtatccaaat cactctgaca 1440
ttttgtggac ccatgatggc aagagggaaa ttcctgctct cgtattctcc cccaaatgga 1500
gcacaaccac agaccctttc tgaagctatg cagtgcacat actctatttg ggatataggc 1560
ttgaactcta gttggacctt tgtcatcccc tacatctcgc ccagtgatta ccgtgaaact 1620
cgggctatta ccaactcagt ttattctgct gatggttggt ttagcttgca caagctgacc 1680
aaaattactc taccacctga ctgcccacag agtccctgta ttctcttttt cgcctctgct 1740
ggtgaggatt acaccctccg tctccctgtt gattgtaatc cttcctacgt gttccactcc 1800
accgacaacg ccgagactgg ggttattgag gcaggtaaca ctgacaccga tttctctggt 1860
gaactggcgg ctcctggctc taaccatact aatgtcaaat tcctgtttga ccgatctcga 1920
ctactgaatg taattaaggt actggagaag gacgccgtct tcccccgtcc tttccccaca 1980
gcaacaggtg cacagcagga cgatggttac ttttgtcttc taacaccccg cccaacagtc 2040
gcttcccgac ccgccactcg tttcggcctg tacgtcaacc cgtctgacag tggcgttctc 2100
gctaacactt cactggattt caatttttac agtttggcct gtttcactta ctttagatca 2160
gaccttgaag tcacggtggt ctcactggag ccagatttgg aattcgccgt ggggtggttc 2220
ccctctggca gtgagtacca ggcttctagc tttgtctacg accaactgca tgtaccctac 2280
cactttactg ggcgcactcc ccgcgctttc accagcaagg gtggaaaggt atctttcgtg 2340
ctcccttgga actctgtctc ttccgtgctt cccgtgcgct gggggggcgc ttccaagctt 2400
tcttctgcca cgcggggtct gccggctcat gctgactggg ggaccattta cgcctttatc 2460
ccccgtccta acgagaagaa aagcaccgct gtaaagcacg tggcggtgta cgttcggtac 2520
aagaacgcgc gtgcttggtg ccccagcatg cttccctttc gcagctacaa gcaaaagatg 2580
ctgatgcaat caggcgacat cgagaccaac cctggccctg gttcaggtaa gccccctgga 2640
gcgctctctc ttatggaaat gcaacagccc aacgtggaca tgggctttga ggctgcggtc 2700
gctaagaaag tggtcgtccc cattaccttc atggttccca acagaccttc tggacttaca 2760
cagtccgctc ttcttgtggc cggccggacc ttcctaatca atgagcatac atggtccaac 2820
ccctcctgga ccagcttcac aatccgtggt gaggtgcaca ctcgtgatga gcctttccaa 2880
acggttcatt ttactcacca tggtcttccc acagatctga tgatggtacg tctcggaccg 2940
ggcaactctt tccctaacaa tctagacaag tttggacttg accagatgcc ggcacgtaac 3000
tcccgtgtgg ttggcgtttc ggctagttac ggtaacttct tcttctctgg gaacttcctc 3060
gggtttgttg actccatcac ctctgaccaa ggaacctatg cgagactttt caggtacagg 3120
gtgacgactt acaagggatg gtgcggttcg gccctggtct gtgaggccgg tggtgtccga 3180
cgcatcattg gcatgcattc tgctggtgcc gctggtatcg gcgccgggac ttacatctca 3240
aaattaggac tgatcaaagc ccttaaacac ctcggtgagc ctctggctac aatgcaagga 3300
ctgatgactg agctagagcc tggagtcacc gtacatgtac cccgaaaatc taaattgaga 3360
aagacgaccg cacacgcggt gtacaaaccg gagtttgaac ctgctgtgtt gtcaaaattt 3420
gatcccagac tgaacaagga tgttgaccta gatgaggtaa tttggtctaa acacaccgcc 3480
aacgtccctt atcaacctcc tttgttctac acatacatgt cagagtacgc tcatcgggtt 3540
ttctcctttt tgggaaaaga caatgacatt ctgaccgtca aagaagcaat cctgggcatc 3600
cctggactag accctatgga tccccacaca gctccgggtt tgccctacgc cattagcggc 3660
cttcgacgta ctgatctcgt cgattttgcg aacggcacgg tagacccggc actggccatg 3720
cagatccaga aattcttaga cggtgactac tctgatcatg tcttccaaac ttttctgaaa 3780
gatgaaatca gaccctcaga gaaggtccgg gcgggaaaaa cccgcattgt cgatgtgccc 3840
tccctggcgc actgcattgt gggcagaatg ctgcttgggc gctttgccgc caagtttcaa 3900
tcccatcctg gctttctcct tggctccgct atcgggtctg accctgatgt cttctggacc 3960
gtcatagggg ctcagctcga gggaagaaag aacacgtatg acgtggacta cagtgccttt 4020
gactcttcac acggcactgg ctccttcgag gctctcatct ctcacttttt caccgtggac 4080
aatggtttca gccctgcgct gggaccgtat ctcagatccc tggctgtctc ggtgcacgct 4140
tacggcgagc gtcgcatcaa gattaccgga ggcctcccct ctggttgtgc cgcgaccagc 4200
ctgctgaaca cagtgctcaa caatgtgatc atcaggactg ctctggcatt gacctacaag 4260
gaatttgaat atgacatggt tgatatcatc gcctacggtg acgaccttct ggttggtacg 4320
gattatgatc tggacttcaa tgaggtggcg cggcgcgctg ccaaactggg gtataagatg 4380
actcctgcca acaagggttc tgtcttccct ccgacttcct ctctctccga tgctgttttt 4440
ctaaaacgca aattcgtcca aaacaatgac ggcttatata aaccagttat ggatttaaag 4500
aatttggaag ccatgctctc ctacttcaaa ccaggaacac tactcgagaa gctgcaatct 4560
gtttctatgt tggctcaaca ttctggaaaa gaagaatacg atagattgat gcaccccttc 4620
gctgactatg gtgccgtacc gagtcacgag tacctgcagg caagatggag ggccttgttc 4680
gactgagcgg ccgc 4694
<210> 25
<211> 1557
<212> PRT
<213> 塞内卡病毒
<400> 25
Met Gly Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly
1 5 10 15
Asn Asn Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn
20 25 30
Ser Val Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly
35 40 45
Asn Ser Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile
50 55 60
Leu Asn Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu
65 70 75 80
Asn Ser Ala Asp Arg Val Ile Thr Gln Thr Ala Gly Asn Thr Ala Ile
85 90 95
Asn Thr Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro
100 105 110
Thr Lys Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr
115 120 125
Phe Thr Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr
130 135 140
Lys Ala Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala
145 150 155 160
Phe Leu Ser Lys Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr
165 170 175
Leu His Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln
180 185 190
Cys Asn Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val
195 200 205
Pro Glu Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu
210 215 220
Gln Glu Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg
225 230 235 240
Thr Gly Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro
245 250 255
Pro Asn Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr
260 265 270
Val Phe Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp
275 280 285
Ile Ser Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr
290 295 300
Gln Asn Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr
305 310 315 320
Lys Glu Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro
325 330 335
Thr Ser Pro Tyr Phe Asn Gly Leu Arg Asn Arg Phe Thr Thr Gly Thr
340 345 350
Asp Glu Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu
355 360 365
Met Phe Leu Ser Thr Ile Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn
370 375 380
Val Arg Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu
385 390 395 400
Leu Gln Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Gly Arg Val Ser
405 410 415
Glu Pro Glu Pro Ala Ser Asp Ala Tyr Val Pro Tyr Val Ala Val Pro
420 425 430
Ala Gln Phe Asp Asp Lys Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser
435 440 445
Asp Pro Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe
450 455 460
Ala Asn Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro
465 470 475 480
Met Met Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly
485 490 495
Ala Gln Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile
500 505 510
Trp Asp Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Ile Pro Tyr Ile
515 520 525
Ser Pro Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr
530 535 540
Ser Ala Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu
545 550 555 560
Pro Pro Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala
565 570 575
Gly Glu Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr
580 585 590
Val Phe His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly
595 600 605
Asn Thr Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn
610 615 620
His Thr Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val
625 630 635 640
Ile Lys Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr
645 650 655
Ala Thr Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro
660 665 670
Arg Pro Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Val
675 680 685
Asn Pro Ser Asp Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn
690 695 700
Phe Tyr Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val
705 710 715 720
Thr Val Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe
725 730 735
Pro Ser Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu
740 745 750
His Val Pro Tyr His Phe Thr Gly Arg Thr Pro Arg Ala Phe Thr Ser
755 760 765
Lys Gly Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser
770 775 780
Val Leu Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr
785 790 795 800
Arg Gly Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Ile
805 810 815
Pro Arg Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val
820 825 830
Tyr Val Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro
835 840 845
Phe Arg Ser Tyr Lys Gln Lys Met Leu Met Gln Ser Gly Asp Ile Glu
850 855 860
Thr Asn Pro Gly Pro Gly Ser Gly Lys Pro Pro Gly Ala Leu Ser Leu
865 870 875 880
Met Glu Met Gln Gln Pro Asn Val Asp Met Gly Phe Glu Ala Ala Val
885 890 895
Ala Lys Lys Val Val Val Pro Ile Thr Phe Met Val Pro Asn Arg Pro
900 905 910
Ser Gly Leu Thr Gln Ser Ala Leu Leu Val Ala Gly Arg Thr Phe Leu
915 920 925
Ile Asn Glu His Thr Trp Ser Asn Pro Ser Trp Thr Ser Phe Thr Ile
930 935 940
Arg Gly Glu Val His Thr Arg Asp Glu Pro Phe Gln Thr Val His Phe
945 950 955 960
Thr His His Gly Leu Pro Thr Asp Leu Met Met Val Arg Leu Gly Pro
965 970 975
Gly Asn Ser Phe Pro Asn Asn Leu Asp Lys Phe Gly Leu Asp Gln Met
980 985 990
Pro Ala Arg Asn Ser Arg Val Val Gly Val Ser Ala Ser Tyr Gly Asn
995 1000 1005
Phe Phe Phe Ser Gly Asn Phe Leu Gly Phe Val Asp Ser Ile Thr
1010 1015 1020
Ser Asp Gln Gly Thr Tyr Ala Arg Leu Phe Arg Tyr Arg Val Thr
1025 1030 1035
Thr Tyr Lys Gly Trp Cys Gly Ser Ala Leu Val Cys Glu Ala Gly
1040 1045 1050
Gly Val Arg Arg Ile Ile Gly Met His Ser Ala Gly Ala Ala Gly
1055 1060 1065
Ile Gly Ala Gly Thr Tyr Ile Ser Lys Leu Gly Leu Ile Lys Ala
1070 1075 1080
Leu Lys His Leu Gly Glu Pro Leu Ala Thr Met Gln Gly Leu Met
1085 1090 1095
Thr Glu Leu Glu Pro Gly Val Thr Val His Val Pro Arg Lys Ser
1100 1105 1110
Lys Leu Arg Lys Thr Thr Ala His Ala Val Tyr Lys Pro Glu Phe
1115 1120 1125
Glu Pro Ala Val Leu Ser Lys Phe Asp Pro Arg Leu Asn Lys Asp
1130 1135 1140
Val Asp Leu Asp Glu Val Ile Trp Ser Lys His Thr Ala Asn Val
1145 1150 1155
Pro Tyr Gln Pro Pro Leu Phe Tyr Thr Tyr Met Ser Glu Tyr Ala
1160 1165 1170
His Arg Val Phe Ser Phe Leu Gly Lys Asp Asn Asp Ile Leu Thr
1175 1180 1185
Val Lys Glu Ala Ile Leu Gly Ile Pro Gly Leu Asp Pro Met Asp
1190 1195 1200
Pro His Thr Ala Pro Gly Leu Pro Tyr Ala Ile Ser Gly Leu Arg
1205 1210 1215
Arg Thr Asp Leu Val Asp Phe Ala Asn Gly Thr Val Asp Pro Ala
1220 1225 1230
Leu Ala Met Gln Ile Gln Lys Phe Leu Asp Gly Asp Tyr Ser Asp
1235 1240 1245
His Val Phe Gln Thr Phe Leu Lys Asp Glu Ile Arg Pro Ser Glu
1250 1255 1260
Lys Val Arg Ala Gly Lys Thr Arg Ile Val Asp Val Pro Ser Leu
1265 1270 1275
Ala His Cys Ile Val Gly Arg Met Leu Leu Gly Arg Phe Ala Ala
1280 1285 1290
Lys Phe Gln Ser His Pro Gly Phe Leu Leu Gly Ser Ala Ile Gly
1295 1300 1305
Ser Asp Pro Asp Val Phe Trp Thr Val Ile Gly Ala Gln Leu Glu
1310 1315 1320
Gly Arg Lys Asn Thr Tyr Asp Val Asp Tyr Ser Ala Phe Asp Ser
1325 1330 1335
Ser His Gly Thr Gly Ser Phe Glu Ala Leu Ile Ser His Phe Phe
1340 1345 1350
Thr Val Asp Asn Gly Phe Ser Pro Ala Leu Gly Pro Tyr Leu Arg
1355 1360 1365
Ser Leu Ala Val Ser Val His Ala Tyr Gly Glu Arg Arg Ile Lys
1370 1375 1380
Ile Thr Gly Gly Leu Pro Ser Gly Cys Ala Ala Thr Ser Leu Leu
1385 1390 1395
Asn Thr Val Leu Asn Asn Val Ile Ile Arg Thr Ala Leu Ala Leu
1400 1405 1410
Thr Tyr Lys Glu Phe Glu Tyr Asp Met Val Asp Ile Ile Ala Tyr
1415 1420 1425
Gly Asp Asp Leu Leu Val Gly Thr Asp Tyr Asp Leu Asp Phe Asn
1430 1435 1440
Glu Val Ala Arg Arg Ala Ala Lys Leu Gly Tyr Lys Met Thr Pro
1445 1450 1455
Ala Asn Lys Gly Ser Val Phe Pro Pro Thr Ser Ser Leu Ser Asp
1460 1465 1470
Ala Val Phe Leu Lys Arg Lys Phe Val Gln Asn Asn Asp Gly Leu
1475 1480 1485
Tyr Lys Pro Val Met Asp Leu Lys Asn Leu Glu Ala Met Leu Ser
1490 1495 1500
Tyr Phe Lys Pro Gly Thr Leu Leu Glu Lys Leu Gln Ser Val Ser
1505 1510 1515
Met Leu Ala Gln His Ser Gly Lys Glu Glu Tyr Asp Arg Leu Met
1520 1525 1530
His Pro Phe Ala Asp Tyr Gly Ala Val Pro Ser His Glu Tyr Leu
1535 1540 1545
Gln Ala Arg Trp Arg Ala Leu Phe Asp
1550 1555
<210> 26
<211> 2618
<212> DNA
<213> 塞内卡病毒
<400> 26
ggatccgcca ccatgggtaa tgttcagaca acctcaaaga atgattttga ttcccgcggc 60
aataatggta acatgacctt caattactac gcaaacactt accagaattc agtagacttc 120
tcgacctcct cgtcggcgtc aggcgccgga cccgggaact cccggggcgg actagcgggt 180
ctcctcacaa atttcagtgg aatcttgaac cctcttggct acctcaaaga tcacaatacc 240
gaagaaatgg aaaactctgc tgatcgagtc ataacgcaaa cggcgggcaa cactgccata 300
aacacgcaat catcactggg tgtgttgtgt gcctacgttg aagacccgac caaatctgac 360
cctccgtcca gcagcacaga tcaacccacc accactttta ctgccatcga caggtggtac 420
actggacgcc tcaattcttg gacaaaagct gtaaaaacct tctcttttca ggccgtcccg 480
ctccctggag ccttcctgtc taaacaggga ggcctcaacg gaggggcctt cacggctacc 540
ctacatagac atttcttaat gaagtgcggg tggcaggtgc aggtccaatg caatttgacg 600
caattccacc aaggtgctct tcttgttgcc atggtccccg aaaccaccct tgatgtcaaa 660
cctgacggca aggcaaagag cttacaggag ctgaatgaag agcagtgggt ggaaatgtct 720
gacgattacc ggaccgggaa aaacatgcct tttcagtctc ttggcacata ctatcggccc 780
cctaactgga cttggggccc caatttcatc aacccctatc aagtaacagt tttcccacac 840
caaattctga acgcgagaac ctctacctcg gtagacataa gtgtcccata catcggggag 900
actcctacac aatcctcaga gacacagaac tcctggaccc tccttgttat ggtgcttgtc 960
cccctggact acaaggaggg agccacaact gacccagaaa ttacattttc tgtaaggcct 1020
acaagtccct acttcaatgg gcttcgtaac cgtttcacga ccgggacgga cgaggaacag 1080
gggcccattc ccacagcacc cagagaaaat tcgcttatgt ttctctcaac catccctgac 1140
gacactgtcc ctgcttacgg gaatgtgcgt acccctcccg tcaattacct ccccggtgaa 1200
ataaccgacc tcttacaact ggcccgtata cccactctca tggcgtttgg gcgggtgtct 1260
gaacccgagc ctgcctcaga cgcatatgtg ccctacgttg ccgttcctgc ccagttcgac 1320
gacaagcctc tcatctcctt cccgatcacc ctttcagatc ctgtctacca gaacaccctg 1380
gtaggcgcca tcagttcgaa cttcgccaac taccgggggt gtatccaaat cactctgaca 1440
ttttgtggac ccatgatggc aagagggaaa ttcctgctct cgtattctcc cccaaatgga 1500
gcacaaccac agaccctttc tgaagctatg cagtgcacat actctatttg ggatataggc 1560
ttgaactcta gttggacctt tgtcatcccc tacatctcgc ccagtgatta ccgtgaaact 1620
cgggctatta ccaactcagt ttattctgct gatggttggt ttagcttgca caagctgacc 1680
aaaattactc taccacctga ctgcccacag agtccctgta ttctcttttt cgcctctgct 1740
ggtgaggatt acaccctccg tctccctgtt gattgtaatc cttcctacgt gttccactcc 1800
accgacaacg ccgagactgg ggttattgag gcaggtaaca ctgacaccga tttctctggt 1860
gaactggcgg ctcctggctc taaccatact aatgtcaaat tcctgtttga ccgatctcga 1920
ctactgaatg taattaaggt actggagaag gacgccgtct tcccccgtcc tttccccaca 1980
gcaacaggtg cacagcagga cgatggttac ttttgtcttc taacaccccg cccaacagtc 2040
gcttcccgac ccgccactcg tttcggcctg tacgtcaacc cgtctgacag tggcgttctc 2100
gctaacactt cactggattt caatttttac agtttggcct gtttcactta ctttagatca 2160
gaccttgaag tcacggtggt ctcactggag ccagatttgg aattcgccgt ggggtggttc 2220
ccctctggca gtgagtacca ggcttctagc tttgtctacg accaactgca tgtaccctac 2280
cactttactg ggcgcactcc ccgcgctttc accagcaagg gtggaaaggt atctttcgtg 2340
ctcccttgga actctgtctc ttccgtgctt cccgtgcgct gggggggcgc ttccaagctt 2400
tcttctgcca cgcggtgtct gccggctcat gctgactggg ggaccattta cgcctttatc 2460
ccccgtccta acgagaagaa aagcaccgct gtaaagcacg tggcggtgta cgttcggtac 2520
aagaacgcgc gtgcttggtg ccccagcatg cttccctttc gcagctacaa gcaaaagatg 2580
ctgatgcaac accaccacca ccaccactga gcggccgc 2618
<210> 27
<211> 855
<212> PRT
<213> 塞内卡病毒
<400> 27
Met Gly Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly
1 5 10 15
Asn Asn Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn
20 25 30
Ser Val Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly
35 40 45
Asn Ser Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile
50 55 60
Leu Asn Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu
65 70 75 80
Asn Ser Ala Asp Arg Val Ile Thr Gln Thr Ala Gly Asn Thr Ala Ile
85 90 95
Asn Thr Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro
100 105 110
Thr Lys Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr
115 120 125
Phe Thr Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr
130 135 140
Lys Ala Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala
145 150 155 160
Phe Leu Ser Lys Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr
165 170 175
Leu His Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln
180 185 190
Cys Asn Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val
195 200 205
Pro Glu Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu
210 215 220
Gln Glu Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg
225 230 235 240
Thr Gly Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro
245 250 255
Pro Asn Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr
260 265 270
Val Phe Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp
275 280 285
Ile Ser Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr
290 295 300
Gln Asn Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr
305 310 315 320
Lys Glu Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro
325 330 335
Thr Ser Pro Tyr Phe Asn Gly Leu Arg Asn Arg Phe Thr Thr Gly Thr
340 345 350
Asp Glu Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu
355 360 365
Met Phe Leu Ser Thr Ile Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn
370 375 380
Val Arg Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu
385 390 395 400
Leu Gln Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Gly Arg Val Ser
405 410 415
Glu Pro Glu Pro Ala Ser Asp Ala Tyr Val Pro Tyr Val Ala Val Pro
420 425 430
Ala Gln Phe Asp Asp Lys Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser
435 440 445
Asp Pro Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe
450 455 460
Ala Asn Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro
465 470 475 480
Met Met Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly
485 490 495
Ala Gln Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile
500 505 510
Trp Asp Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Ile Pro Tyr Ile
515 520 525
Ser Pro Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr
530 535 540
Ser Ala Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu
545 550 555 560
Pro Pro Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala
565 570 575
Gly Glu Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr
580 585 590
Val Phe His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly
595 600 605
Asn Thr Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn
610 615 620
His Thr Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val
625 630 635 640
Ile Lys Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr
645 650 655
Ala Thr Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro
660 665 670
Arg Pro Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Val
675 680 685
Asn Pro Ser Asp Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn
690 695 700
Phe Tyr Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val
705 710 715 720
Thr Val Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe
725 730 735
Pro Ser Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu
740 745 750
His Val Pro Tyr His Phe Thr Gly Arg Thr Pro Arg Ala Phe Thr Ser
755 760 765
Lys Gly Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser
770 775 780
Val Leu Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr
785 790 795 800
Arg Cys Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Ile
805 810 815
Pro Arg Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val
820 825 830
Tyr Val Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro
835 840 845
Phe Arg Ser Tyr Lys Gln Lys
850 855
<210> 28
<211> 2618
<212> DNA
<213> 塞内卡病毒
<400> 28
ggatccgcca ccatgggcaa cgttcaaact acctccaaga atgattttga ctcccgcggc 60
aacaacggca acatgacttt taactactac gccaatacgt atcaaaactc tgttgatttc 120
tcgacatcga gttccgcttc cggcgcggga cctggaaatt cccgcggtgg actggccggt 180
ctgctcacaa acttttccgg tatcctgaac cccctcggtt atctgaaaga tcacaatacg 240
gaagagatgg agaactctgc cgatcgtgtg attacgcaga cagctggtaa cacggctatc 300
aacactcaat cgtctctggg agtactctgt gcttacgtcg aggacccaac aaaatccgac 360
cctccatctt cctcgaccga tcaacctacg actaccttca cggccataga caggtggtat 420
acaggtcgcc tgaattcgtg gacaaaggct gttaaaacct ttagcttcca ggctgtgcca 480
ttgcccggtg ctttcctttc ccgccagggc ggcctcaacg gtggagcttt tactgctaca 540
ctgcacagac actttctgat gaaatgcggt tggcaggtgc aggtacagtg caatttgact 600
caattccacc aaggtgcact tctcgttgct atggttcccg agactacgct tgacgttaag 660
cctgacggca aggccaagtc tctccaagag ctgaatgagg aacagtgggt tgagatgagc 720
gatgactata gaaccggtaa aaacatgcca ttccagtccc tgggcacata ctacagaccc 780
ccaaattgga cttggggccc gaactttatc aatccgtatc aggtcaccgt gtttccacac 840
caaatcctga atgccaggac tagtaccagc gtcgatatta gcgtgcccta tatcggcgaa 900
acgccaaccc aatcctccga aactcagaac agctggacgc ttctggtaat ggtgttggta 960
cccttggatt ataaggaggg agccactacc gaccctgaaa tcactttttc ggtaaggccc 1020
actagccctt acttcaacgg actgcgcaac cgtttcacca ccggcactga tgaggagcaa 1080
ggccctatcc ctactgcccc cagagaaaat agcctgatgt ttctgagcac aattcctgac 1140
gacaccgtac ctgcctatgg taacgttcgt acgcctcccg taaactacct gcctggtgaa 1200
attacggacc tcttgcagct ggcccgcatc cctacactga tggccttcgg tcgtgtcagt 1260
gagcccgaac cagccagcga cgcttacgtt ccatatgttg cggtacctgc tcagttcgac 1320
gacaagccgt tgataagttt cccaatcact ttgagcgacc ctgtatacca gaacactttg 1380
gttggagcta tctcctcgaa ctttgcgaac taccgtggtt gtattcaaat cacccttaca 1440
ttctgcggcc cgatgatggc tcgtggcaag ttcctgttga gctactcccc ccccaacgga 1500
gcacaaccac agacactgtc cgaggccatg cagtgcacat actccatctg ggatatcggt 1560
ctcaacagct catggacctt tgtaatacca tacatctcgc catccgatta tagagagacc 1620
cgcgccatca ccaacagtgt gtactcagcc gatggatggt tcagtctcca taagcttaca 1680
aagatcactc tgccccccga ctgcccacaa tcaccctgca tattgttctt tgcctcagct 1740
ggtgaagatt acacgcttcg tttgcccgtc gactgtaacc cgtcttacgt gttccactcc 1800
acggacaatg ctgagaccgg tgtaattgag gctggtaaca ccgacacgga tttctctggt 1860
gagctggcgg ctcccggttc taaccatacc aacgtgaagt tccttttcga ccgttcacgt 1920
cttttgaacg taatcaaggt cttggaaaag gacgctgtgt tccctcgccc attccccaca 1980
gcaacgggag cacaacaaga cgacggctat ttctgcctgc tgacaccacg tcctactgtg 2040
gctagccgtc cggccacacg ctttggtctc tacgttaacc ctagcgactc tggtgtactg 2100
gctaacacct ccctggactt caatttctac tctctggcct gcttcacgta cttcaggagc 2160
gacctggagg tcactgtggt gtctctggaa ccagatctgg aatttgcggt aggatggttc 2220
ccttcaggaa gcgagtacca ggcatcgtcc tttgtgtacg accaacttca tgttccctac 2280
catttcaccg gtagaacccc acgtgccttc accagtaagg gaggcaaagt ttcttttgta 2340
ctgccctgga attctgtcag ttccgttctc ccggtccgct ggggcggagc gtcaaagctc 2400
tcatccgcga cccgcggatt gcccgcacac gcggattggg gaactatcta cgctttcatt 2460
ccacgcccta atgaaaagaa gtctacagca gtgaagcacg tggccgtcta tgtgcgttac 2520
aagaatgcaa gggcgtggtg tccgtctatg ttgccattcc gtagctataa acagaagatg 2580
cttatgcaac accaccacca ccaccactga gcggccgc 2618
<210> 29
<211> 865
<212> PRT
<213> 塞内卡病毒
<400> 29
Met Gly Asn Val Gln Thr Thr Ser Lys Asn Asp Phe Asp Ser Arg Gly
1 5 10 15
Asn Asn Gly Asn Met Thr Phe Asn Tyr Tyr Ala Asn Thr Tyr Gln Asn
20 25 30
Ser Val Asp Phe Ser Thr Ser Ser Ser Ala Ser Gly Ala Gly Pro Gly
35 40 45
Asn Ser Arg Gly Gly Leu Ala Gly Leu Leu Thr Asn Phe Ser Gly Ile
50 55 60
Leu Asn Pro Leu Gly Tyr Leu Lys Asp His Asn Thr Glu Glu Met Glu
65 70 75 80
Asn Ser Ala Asp Arg Val Ile Thr Gln Thr Ala Gly Asn Thr Ala Ile
85 90 95
Asn Thr Gln Ser Ser Leu Gly Val Leu Cys Ala Tyr Val Glu Asp Pro
100 105 110
Thr Lys Ser Asp Pro Pro Ser Ser Ser Thr Asp Gln Pro Thr Thr Thr
115 120 125
Phe Thr Ala Ile Asp Arg Trp Tyr Thr Gly Arg Leu Asn Ser Trp Thr
130 135 140
Lys Ala Val Lys Thr Phe Ser Phe Gln Ala Val Pro Leu Pro Gly Ala
145 150 155 160
Phe Leu Ser Arg Gln Gly Gly Leu Asn Gly Gly Ala Phe Thr Ala Thr
165 170 175
Leu His Arg His Phe Leu Met Lys Cys Gly Trp Gln Val Gln Val Gln
180 185 190
Cys Asn Leu Thr Gln Phe His Gln Gly Ala Leu Leu Val Ala Met Val
195 200 205
Pro Glu Thr Thr Leu Asp Val Lys Pro Asp Gly Lys Ala Lys Ser Leu
210 215 220
Gln Glu Leu Asn Glu Glu Gln Trp Val Glu Met Ser Asp Asp Tyr Arg
225 230 235 240
Thr Gly Lys Asn Met Pro Phe Gln Ser Leu Gly Thr Tyr Tyr Arg Pro
245 250 255
Pro Asn Trp Thr Trp Gly Pro Asn Phe Ile Asn Pro Tyr Gln Val Thr
260 265 270
Val Phe Pro His Gln Ile Leu Asn Ala Arg Thr Ser Thr Ser Val Asp
275 280 285
Ile Ser Val Pro Tyr Ile Gly Glu Thr Pro Thr Gln Ser Ser Glu Thr
290 295 300
Gln Asn Ser Trp Thr Leu Leu Val Met Val Leu Val Pro Leu Asp Tyr
305 310 315 320
Lys Glu Gly Ala Thr Thr Asp Pro Glu Ile Thr Phe Ser Val Arg Pro
325 330 335
Thr Ser Pro Tyr Phe Asn Gly Leu Arg Asn Arg Phe Thr Thr Gly Thr
340 345 350
Asp Glu Glu Gln Gly Pro Ile Pro Thr Ala Pro Arg Glu Asn Ser Leu
355 360 365
Met Phe Leu Ser Thr Ile Pro Asp Asp Thr Val Pro Ala Tyr Gly Asn
370 375 380
Val Arg Thr Pro Pro Val Asn Tyr Leu Pro Gly Glu Ile Thr Asp Leu
385 390 395 400
Leu Gln Leu Ala Arg Ile Pro Thr Leu Met Ala Phe Gly Arg Val Ser
405 410 415
Glu Pro Glu Pro Ala Ser Asp Ala Tyr Val Pro Tyr Val Ala Val Pro
420 425 430
Ala Gln Phe Asp Asp Lys Pro Leu Ile Ser Phe Pro Ile Thr Leu Ser
435 440 445
Asp Pro Val Tyr Gln Asn Thr Leu Val Gly Ala Ile Ser Ser Asn Phe
450 455 460
Ala Asn Tyr Arg Gly Cys Ile Gln Ile Thr Leu Thr Phe Cys Gly Pro
465 470 475 480
Met Met Ala Arg Gly Lys Phe Leu Leu Ser Tyr Ser Pro Pro Asn Gly
485 490 495
Ala Gln Pro Gln Thr Leu Ser Glu Ala Met Gln Cys Thr Tyr Ser Ile
500 505 510
Trp Asp Ile Gly Leu Asn Ser Ser Trp Thr Phe Val Ile Pro Tyr Ile
515 520 525
Ser Pro Ser Asp Tyr Arg Glu Thr Arg Ala Ile Thr Asn Ser Val Tyr
530 535 540
Ser Ala Asp Gly Trp Phe Ser Leu His Lys Leu Thr Lys Ile Thr Leu
545 550 555 560
Pro Pro Asp Cys Pro Gln Ser Pro Cys Ile Leu Phe Phe Ala Ser Ala
565 570 575
Gly Glu Asp Tyr Thr Leu Arg Leu Pro Val Asp Cys Asn Pro Ser Tyr
580 585 590
Val Phe His Ser Thr Asp Asn Ala Glu Thr Gly Val Ile Glu Ala Gly
595 600 605
Asn Thr Asp Thr Asp Phe Ser Gly Glu Leu Ala Ala Pro Gly Ser Asn
610 615 620
His Thr Asn Val Lys Phe Leu Phe Asp Arg Ser Arg Leu Leu Asn Val
625 630 635 640
Ile Lys Val Leu Glu Lys Asp Ala Val Phe Pro Arg Pro Phe Pro Thr
645 650 655
Ala Thr Gly Ala Gln Gln Asp Asp Gly Tyr Phe Cys Leu Leu Thr Pro
660 665 670
Arg Pro Thr Val Ala Ser Arg Pro Ala Thr Arg Phe Gly Leu Tyr Val
675 680 685
Asn Pro Ser Asp Ser Gly Val Leu Ala Asn Thr Ser Leu Asp Phe Asn
690 695 700
Phe Tyr Ser Leu Ala Cys Phe Thr Tyr Phe Arg Ser Asp Leu Glu Val
705 710 715 720
Thr Val Val Ser Leu Glu Pro Asp Leu Glu Phe Ala Val Gly Trp Phe
725 730 735
Pro Ser Gly Ser Glu Tyr Gln Ala Ser Ser Phe Val Tyr Asp Gln Leu
740 745 750
His Val Pro Tyr His Phe Thr Gly Arg Thr Pro Arg Ala Phe Thr Ser
755 760 765
Lys Gly Gly Lys Val Ser Phe Val Leu Pro Trp Asn Ser Val Ser Ser
770 775 780
Val Leu Pro Val Arg Trp Gly Gly Ala Ser Lys Leu Ser Ser Ala Thr
785 790 795 800
Arg Gly Leu Pro Ala His Ala Asp Trp Gly Thr Ile Tyr Ala Phe Ile
805 810 815
Pro Arg Pro Asn Glu Lys Lys Ser Thr Ala Val Lys His Val Ala Val
820 825 830
Tyr Val Arg Tyr Lys Asn Ala Arg Ala Trp Cys Pro Ser Met Leu Pro
835 840 845
Phe Arg Ser Tyr Lys Gln Lys Met Leu Met Gln His His His His His
850 855 860
His
865
<210> 30
<211> 651
<212> DNA
<213> 塞内卡病毒
<400> 30
actagtatgc agcccaacgt ggacatgggc tttgaggctg cggtcgctaa gaaagtggtc 60
gtccccatta ccttcatggt tcccaacaga ccttctggac ttacacagtc cgctcttctt 120
gtggccggcc ggaccttcat aatcaatgag catacatggt ccaacccctc ctggaccagc 180
ttcacaatcc gtggtgaggt gcacactcgt gatgagcctt tccaaacggt tcattttact 240
caccatggtc ttcccacaga tctgatgatg gtacgtctcg gaccgggcaa ctctttccct 300
aacaatctag acaagtttgg acttgaccag atgccggcac gtaactcccg tgtggttggc 360
gtttcggcta gttacggtaa cttcttcttc tctgggaact tcctcgggtt tgttgactcc 420
atcacctctg accaaggaac ctatgcgaga cttttcaggt acagggtgac gacttacaag 480
ggatggtgcg gttcggccct ggtctgtgag gccggtggtg tccgacgcat cattggcatg 540
cattctgctg gtgccgctgg tatcggcgcc gggacttaca tctcaaaatt aggactgatc 600
aaagccctta aacacctcgg tgagcctctg gctacaatgc aatgagagct c 651
<210> 31
<211> 212
<212> PRT
<213> 塞内卡病毒
<400> 31
Met Gln Pro Asn Val Asp Met Gly Phe Glu Ala Ala Val Ala Lys Lys
1 5 10 15
Val Val Val Pro Ile Thr Phe Met Val Pro Asn Arg Pro Ser Gly Leu
20 25 30
Thr Gln Ser Ala Leu Leu Val Ala Gly Arg Thr Phe Ile Ile Asn Glu
35 40 45
His Thr Trp Ser Asn Pro Ser Trp Thr Ser Phe Thr Ile Arg Gly Glu
50 55 60
Val His Thr Arg Asp Glu Pro Phe Gln Thr Val His Phe Thr His His
65 70 75 80
Gly Leu Pro Thr Asp Leu Met Met Val Arg Leu Gly Pro Gly Asn Ser
85 90 95
Phe Pro Asn Asn Leu Asp Lys Phe Gly Leu Asp Gln Met Pro Ala Arg
100 105 110
Asn Ser Arg Val Val Gly Val Ser Ala Ser Tyr Gly Asn Phe Phe Phe
115 120 125
Ser Gly Asn Phe Leu Gly Phe Val Asp Ser Ile Thr Ser Asp Gln Gly
130 135 140
Thr Tyr Ala Arg Leu Phe Arg Tyr Arg Val Thr Thr Tyr Lys Gly Trp
145 150 155 160
Cys Gly Ser Ala Leu Val Cys Glu Ala Gly Gly Val Arg Arg Ile Ile
165 170 175
Gly Met His Ser Ala Gly Ala Ala Gly Ile Gly Ala Gly Thr Tyr Ile
180 185 190
Ser Lys Leu Gly Leu Ile Lys Ala Leu Lys His Leu Gly Glu Pro Leu
195 200 205
Ala Thr Met Gln
210
<210> 32
<211> 3489
<212> DNA
<213> 塞内卡病毒
<400> 32
ggatccgcca ccatgggtaa tgttcagaca acctcaaaga atgattttga ttcccgcggc 60
aataatggta acatgacctt caattactac gcaaacactt accagaattc agtagacttc 120
tcgacctcct cgtcggcgtc aggcgccgga cccgggaact cccggggcgg actagcgggt 180
ctcctcacaa atttcagtgg aatcttgaac cctcttggct acctcaaaga tcacaatacc 240
gaagaaatgg aaaactctgc tgatcgagtc ataacgcaaa cggcgggcaa cactgccata 300
aacacgcaat catcactggg tgtgttgtgt gcctacgttg aagacccgac caaatctgac 360
cctccgtcca gcagcacaga tcaacccacc accactttta ctgccatcga caggtggtac 420
actggacgcc tcaattcttg gacaaaagct gtaaaaacct tctcttttca ggccgtcccg 480
ctccctggag ccttcctgtc taaacaggga ggcctcaacg gaggggcctt cacggctacc 540
ctacatagac atttcttaat gaagtgcggg tggcaggtgc aggtccaatg caatttgacg 600
caattccacc aaggtgctct tcttgttgcc atggtccccg aaaccaccct tgatgtcaaa 660
cctgacggca aggcaaagag cttacaggag ctgaatgaag agcagtgggt ggaaatgtct 720
gacgattacc ggaccgggaa aaacatgcct tttcagtctc ttggcacata ctatcggccc 780
cctaactgga cttggggccc caatttcatc aacccctatc aagtaacagt tttcccacac 840
caaattctga acgcgagaac ctctacctcg gtagacataa gtgtcccata catcggggag 900
actcctacac aatcctcaga gacacagaac tcctggaccc tccttgttat ggtgcttgtc 960
cccctggact acaaggaggg agccacaact gacccagaaa ttacattttc tgtaaggcct 1020
acaagtccct acttcaatgg gcttcgtaac cgtttcacga ccgggacgga cgaggaacag 1080
gggcccattc ccacagcacc cagagaaaat tcgcttatgt ttctctcaac catccctgac 1140
gacactgtcc ctgcttacgg gaatgtgcgt acccctcccg tcaattacct ccccggtgaa 1200
ataaccgacc tcttacaact ggcccgtata cccactctca tggcgtttgg gcgggtgtct 1260
gaacccgagc ctgcctcaga cgcatatgtg ccctacgttg ccgttcctgc ccagttcgac 1320
gacaagcctc tcatctcctt cccgatcacc ctttcagatc ctgtctacca gaacaccctg 1380
gtaggcgcca tcagttcgaa cttcgccaac taccgggggt gtatccaaat cactctgaca 1440
ttttgtggac ccatgatggc aagagggaaa ttcctgctct cgtattctcc cccaaatgga 1500
gcacaaccac agaccctttc tgaagctatg cagtgcacat actctatttg ggatataggc 1560
ttgaactcta gttggacctt tgtcatcccc tacatctcgc ccagtgatta ccgtgaaact 1620
cgggctatta ccaactcagt ttattctgct gatggttggt ttagcttgca caagctgacc 1680
aaaattactc taccacctga ctgcccacag agtccctgta ttctcttttt cgcctctgct 1740
ggtgaggatt acaccctccg tctccctgtt gattgtaatc cttcctacgt gttccactcc 1800
accgacaacg ccgagactgg ggttattgag gcaggtaaca ctgacaccga tttctctggt 1860
gaactggcgg ctcctggctc taaccatact aatgtcaaat tcctgtttga ccgatctcga 1920
ctactgaatg taattaaggt actggagaag gacgccgtct tcccccgtcc tttccccaca 1980
gcaacaggtg cacagcagga cgatggttac ttttgtcttc taacaccccg cccaacagtc 2040
gcttcccgac ccgccactcg tttcggcctg tacgtcaacc cgtctgacag tggcgttctc 2100
gctaacactt cactggattt caatttttac agtttggcct gtttcactta ctttagatca 2160
gaccttgaag tcacggtggt ctcactggag ccagatttgg aattcgccgt ggggtggttc 2220
ccctctggca gtgagtacca ggcttctagc tttgtctacg accaactgca tgtaccctac 2280
cactttactg ggcgcactcc ccgcgctttc accagcaagg gtggaaaggt atctttcgtg 2340
ctcccttgga actctgtctc ttccgtgctt cccgtgcgct gggggggcgc ttccaagctt 2400
tcttctgcca cgcggtgtct gccggctcat gctgactggg ggaccattta cgcctttatc 2460
ccccgtccta acgagaagaa aagcaccgct gtaaagcacg tggcggtgta cgttcggtac 2520
aagaacgcgc gtgcttggtg ccccagcatg cttccctttc gcagctacaa gcaaaagatg 2580
ctgatgcaac accaccacca ccaccactga gcggccgcga actgtggagc cagggcggcc 2640
ttggccaccc tggcttactg taacagaaaa aagagtaaaa ggcgacagct cgcttgccaa 2700
ttgtcctgtt acgtactctg tggtttcacg aggttgtcat caccaaaggt aacctttttt 2760
tttgtcctcg ccgacaaaac gacatcttaa taaccaagca acgttcgata aagaaaaaaa 2820
ctcgtcctta agtcgcgaac tagtatgcag cccaacgtgg acatgggctt tgaggctgcg 2880
gtcgctaaga aagtggtcgt ccccattacc ttcatggttc ccaacagacc ttctggactt 2940
acacagtccg ctcttcttgt ggccggccgg accttcataa tcaatgagca tacatggtcc 3000
aacccctcct ggaccagctt cacaatccgt ggtgaggtgc acactcgtga tgagcctttc 3060
caaacggttc attttactca ccatggtctt cccacagatc tgatgatggt acgtctcgga 3120
ccgggcaact ctttccctaa caatctagac aagtttggac ttgaccagat gccggcacgt 3180
aactcccgtg tggttggcgt ttcggctagt tacggtaact tcttcttctc tgggaacttc 3240
ctcgggtttg ttgactccat cacctctgac caaggaacct atgcgagact tttcaggtac 3300
agggtgacga cttacaaggg atggtgcggt tcggccctgg tctgtgaggc cggtggtgtc 3360
cgacgcatca ttggcatgca ttctgctggt gccgctggta tcggcgccgg gacttacatc 3420
tcaaaattag gactgatcaa agcccttaaa cacctcggtg agcctctggc tacaatgcaa 3480
tgagagctc 3489
<210> 33
<211> 3489
<212> DNA
<213> 塞内卡病毒
<400> 33
ggatccgcca ccatgggcaa cgttcaaact acctccaaga atgattttga ctcccgcggc 60
aacaacggca acatgacttt taactactac gccaatacgt atcaaaactc tgttgatttc 120
tcgacatcga gttccgcttc cggcgcggga cctggaaatt cccgcggtgg actggccggt 180
ctgctcacaa acttttccgg tatcctgaac cccctcggtt atctgaaaga tcacaatacg 240
gaagagatgg agaactctgc cgatcgtgtg attacgcaga cagctggtaa cacggctatc 300
aacactcaat cgtctctggg agtactctgt gcttacgtcg aggacccaac aaaatccgac 360
cctccatctt cctcgaccga tcaacctacg actaccttca cggccataga caggtggtat 420
acaggtcgcc tgaattcgtg gacaaaggct gttaaaacct ttagcttcca ggctgtgcca 480
ttgcccggtg ctttcctttc ccgccagggc ggcctcaacg gtggagcttt tactgctaca 540
ctgcacagac actttctgat gaaatgcggt tggcaggtgc aggtacagtg caatttgact 600
caattccacc aaggtgcact tctcgttgct atggttcccg agactacgct tgacgttaag 660
cctgacggca aggccaagtc tctccaagag ctgaatgagg aacagtgggt tgagatgagc 720
gatgactata gaaccggtaa aaacatgcca ttccagtccc tgggcacata ctacagaccc 780
ccaaattgga cttggggccc gaactttatc aatccgtatc aggtcaccgt gtttccacac 840
caaatcctga atgccaggac tagtaccagc gtcgatatta gcgtgcccta tatcggcgaa 900
acgccaaccc aatcctccga aactcagaac agctggacgc ttctggtaat ggtgttggta 960
cccttggatt ataaggaggg agccactacc gaccctgaaa tcactttttc ggtaaggccc 1020
actagccctt acttcaacgg actgcgcaac cgtttcacca ccggcactga tgaggagcaa 1080
ggccctatcc ctactgcccc cagagaaaat agcctgatgt ttctgagcac aattcctgac 1140
gacaccgtac ctgcctatgg taacgttcgt acgcctcccg taaactacct gcctggtgaa 1200
attacggacc tcttgcagct ggcccgcatc cctacactga tggccttcgg tcgtgtcagt 1260
gagcccgaac cagccagcga cgcttacgtt ccatatgttg cggtacctgc tcagttcgac 1320
gacaagccgt tgataagttt cccaatcact ttgagcgacc ctgtatacca gaacactttg 1380
gttggagcta tctcctcgaa ctttgcgaac taccgtggtt gtattcaaat cacccttaca 1440
ttctgcggcc cgatgatggc tcgtggcaag ttcctgttga gctactcccc ccccaacgga 1500
gcacaaccac agacactgtc cgaggccatg cagtgcacat actccatctg ggatatcggt 1560
ctcaacagct catggacctt tgtaatacca tacatctcgc catccgatta tagagagacc 1620
cgcgccatca ccaacagtgt gtactcagcc gatggatggt tcagtctcca taagcttaca 1680
aagatcactc tgccccccga ctgcccacaa tcaccctgca tattgttctt tgcctcagct 1740
ggtgaagatt acacgcttcg tttgcccgtc gactgtaacc cgtcttacgt gttccactcc 1800
acggacaatg ctgagaccgg tgtaattgag gctggtaaca ccgacacgga tttctctggt 1860
gagctggcgg ctcccggttc taaccatacc aacgtgaagt tccttttcga ccgttcacgt 1920
cttttgaacg taatcaaggt cttggaaaag gacgctgtgt tccctcgccc attccccaca 1980
gcaacgggag cacaacaaga cgacggctat ttctgcctgc tgacaccacg tcctactgtg 2040
gctagccgtc cggccacacg ctttggtctc tacgttaacc ctagcgactc tggtgtactg 2100
gctaacacct ccctggactt caatttctac tctctggcct gcttcacgta cttcaggagc 2160
gacctggagg tcactgtggt gtctctggaa ccagatctgg aatttgcggt aggatggttc 2220
ccttcaggaa gcgagtacca ggcatcgtcc tttgtgtacg accaacttca tgttccctac 2280
catttcaccg gtagaacccc acgtgccttc accagtaagg gaggcaaagt ttcttttgta 2340
ctgccctgga attctgtcag ttccgttctc ccggtccgct ggggcggagc gtcaaagctc 2400
tcatccgcga cccgcggatt gcccgcacac gcggattggg gaactatcta cgctttcatt 2460
ccacgcccta atgaaaagaa gtctacagca gtgaagcacg tggccgtcta tgtgcgttac 2520
aagaatgcaa gggcgtggtg tccgtctatg ttgccattcc gtagctataa acagaagatg 2580
cttatgcaac accaccacca ccaccactga gcggccgcga actgtggagc cagggcggcc 2640
ttggccaccc tggcttactg taacagaaaa aagagtaaaa ggcgacagct cgcttgccaa 2700
ttgtcctgtt acgtactctg tggtttcacg aggttgtcat caccaaaggt aacctttttt 2760
tttgtcctcg ccgacaaaac gacatcttaa taaccaagca acgttcgata aagaaaaaaa 2820
ctcgtcctta agtcgcgaac tagtatgcag cccaacgtgg acatgggctt tgaggctgcg 2880
gtcgctaaga aagtggtcgt ccccattacc ttcatggttc ccaacagacc ttctggactt 2940
acacagtccg ctcttcttgt ggccggccgg accttcataa tcaatgagca tacatggtcc 3000
aacccctcct ggaccagctt cacaatccgt ggtgaggtgc acactcgtga tgagcctttc 3060
caaacggttc attttactca ccatggtctt cccacagatc tgatgatggt acgtctcgga 3120
ccgggcaact ctttccctaa caatctagac aagtttggac ttgaccagat gccggcacgt 3180
aactcccgtg tggttggcgt ttcggctagt tacggtaact tcttcttctc tgggaacttc 3240
ctcgggtttg ttgactccat cacctctgac caaggaacct atgcgagact tttcaggtac 3300
agggtgacga cttacaaggg atggtgcggt tcggccctgg tctgtgaggc cggtggtgtc 3360
cgacgcatca ttggcatgca ttctgctggt gccgctggta tcggcgccgg gacttacatc 3420
tcaaaattag gactgatcaa agcccttaaa cacctcggtg agcctctggc tacaatgcaa 3480
tgagagctc 3489
<210> 34
<211> 26
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 34
ggatccgcca ccatgggtaa tgttca 26
<210> 35
<211> 58
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 35
gcggccgctc agtggtggtg gtggtggtgt tgcatcagca tcttttgctt gtagctgc 58
<210> 36
<211> 22
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 36
ggatccgcca ccatgggcaa cg 22
<210> 37
<211> 60
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 37
gcggccgctc agtggtggtg gtggtggtgt tgcataagca tcttctgttt atagctacgg 60
<210> 38
<211> 33
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 38
actagtatgc agcccaacgt ggacatgggc ttt 33
<210> 39
<211> 35
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 39
gagctctcat tgcattgtag ccagaggctc accga 35
<210> 40
<211> 41
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 40
cttcctacgt gcctcagggg gttgacaacg ccgagactgg g 41
<210> 41
<211> 41
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 41
cccagtctcg gcgttgtcaa ccccctgagg cacgtaggaa g 41
<210> 42
<211> 35
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 42
tacaatgcaa ggactgatga ctgagctaga gcctg 35
<210> 43
<211> 31
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 43
tcagtcatca gtccttgcat tgtagccaga g 31
<210> 44
<211> 32
<212> DNA
<213> 人工序列
<220>
<223> 引物
<400> 44
gcggccgctc agtcgaacaa ggccctccat ct 32
<210> 45
<211> 1389
<212> DNA
<213> 塞内卡病毒
<400> 45
ggactgatga ctgagctaga gcctggagtc accgtacatg taccccgaaa atctaaattg 60
agaaagacga ccgcacacgc ggtgtacaaa ccggagtttg aacctgctgt gttgtcaaaa 120
tttgatccca gactgaacaa ggatgttgac ctagatgagg taatttggtc taaacacacc 180
gccaacgtcc cttatcaacc tcctttgttc tacacataca tgtcagagta cgctcatcgg 240
gttttctcct ttttgggaaa agacaatgac attctgaccg tcaaagaagc aatcctgggc 300
atccctggac tagaccctat ggatccccac acagctccgg gtttgcccta cgccattagc 360
ggccttcgac gtactgatct cgtcgatttt gcgaacggca cggtagaccc ggcactggcc 420
atgcagatcc agaaattctt agacggtgac tactctgatc atgtcttcca aacttttctg 480
aaagatgaaa tcagaccctc agagaaggtc cgggcgggaa aaacccgcat tgtcgatgtg 540
ccctccctgg cgcactgcat tgtgggcaga atgctgcttg ggcgctttgc cgccaagttt 600
caatcccatc ctggctttct ccttggctcc gctatcgggt ctgaccctga tgtcttctgg 660
accgtcatag gggctcagct cgagggaaga aagaacacgt atgacgtgga ctacagtgcc 720
tttgactctt cacacggcac tggctccttc gaggctctca tctctcactt tttcaccgtg 780
gacaatggtt tcagccctgc gctgggaccg tatctcagat ccctggctgt ctcggtgcac 840
gcttacggcg agcgtcgcat caagattacc ggaggcctcc cctctggttg tgccgcgacc 900
agcctgctga acacagtgct caacaatgtg atcatcagga ctgctctggc attgacctac 960
aaggaatttg aatatgacat ggttgatatc atcgcctacg gtgacgacct tctggttggt 1020
acggattatg atctggactt caatgaggtg gcgcggcgcg ctgccaaact ggggtataag 1080
atgactcctg ccaacaaggg ttctgtcttc cctccgactt cctctctctc cgatgctgtt 1140
tttctaaaac gcaaattcgt ccaaaacaat gacggcttat ataaaccagt tatggattta 1200
aagaatttgg aagccatgct ctcctacttc aaaccaggaa cactactcga gaagctgcaa 1260
tctgtttcta tgttggctca acattctgga aaagaagaat acgatagatt gatgcacccc 1320
ttcgctgact atggtgccgt accgagtcac gagtacctgc aggcaagatg gagggccttg 1380
ttcgactga 1389

Claims (16)

1.一种核酸，其包含具有选自以下的核苷酸序列的多核苷酸：
(a)选自SEQ ID NO：1和SEQ ID NO：2的核苷酸序列；
(b)与SEQ ID NO：1或SEQ ID NO：2至少80％、至少85％、至少90％、至少95％、至少96％、至少97％、至少98％、至少99％、至少99.1％、至少99.2％、至少99.3％、至少99.4％、至少99.5％、至少99.6％、至少99.7％、至少99.8％、至少99.9％相同的核苷酸序列；
(c)编码具有选自SEQ ID NO：3的氨基酸序列的多肽的核苷酸序列；
(d)编码具有氨基酸序列的多肽的核苷酸序列，所述氨基酸序列与SEQ ID NO：3至少80％、至少85％、至少90％、至少95％、至少96％、至少97％、至少98％、至少99％、至少99.1％、至少99.2％、至少99.3％、至少99.4％、至少99.5％、至少99.6％、至少99.7％、至少99.8％、至少99.9％相同；
(e)(a)至(d)的任何核苷酸序列的互补链；
(f)(a)至(e)的任何核苷酸序列的DNA等价物。
2.根据权利要求1的核酸，其中所述核酸编码塞内卡病毒A(SVA)。
3.根据权利要求1或权利要求2的核酸，其中所述塞内卡病毒A(SVA)能够在对象中诱导感染，特别是在具有与此类感染相关或由此类感染引起的临床体征的对象中诱导感染，所述临床体征选自：特发性水疱病，水疱病例如位于口鼻部、口腔粘膜和/或其中皮肤和蹄壁相交处(冠状带)的开放或闭合性水泡或病变，甲床出血，伴随在冠状带处或周围的发红和肿胀的突然/急性跛行；冠状带溃疡和蹄脱落；以及突然停止进食，嗜睡，厌食和/或发烧高达华氏105°(摄氏～40.6°)的繁殖雌性；优选地，所述对象是猪。
4.一种塞内卡病毒A(SVA)，其基因组包含根据权利要求1(a)至(e)的核糖核酸。
5.根据权利要求4的塞内卡病毒A(SVA)，其中所述塞内卡病毒是减毒的或杀死的/灭活的。
6.一种载体，其包含根据权利要求1至3中任一项的核酸。
7.一种宿主细胞，其包含根据权利要求6的载体。
8.一种多肽，其具有选自以下的氨基酸序列：
(a)具有由权利要求1(a)至(b)的核苷酸编码的氨基酸序列的多肽；
(b)具有选自SEQ ID NO：3的氨基酸序列的多肽；
(c)具有与SEQ ID NO：3至少80％、至少85％、至少90％、至少95％、至少96％、至少97％、至少98％、至少99％、至少99.1％、至少99.2％、至少99.3％、至少99.4％、至少99.5％、至少99.6％、至少99.7％、至少99.8％、至少99.9％相同的氨基酸序列的多肽；
(d)根据(a)、(b)和/或(c)的多肽的多肽片段；
(e)多肽片段，其包含SEQ ID NO：3的序列中包括的至少5个，优选8个，更优选10个，甚至更优选15个邻接氨基酸残基；
(f)多肽序列，其是具有氨基酸序列的P1-2A-P3多肽，所述氨基酸序列由选自以下的核苷酸序列编码：SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22、SEQ ID NO:24、SEQ ID NO:32、SEQ ID NO:33；
(g)多肽序列，其是具有氨基酸序列的P1-2A-P3多肽，所述氨基酸序列由与SEQ ID NO:18、SEQ ID NO:20、SEQ ID NO:22、SEQ ID NO:24、SEQ ID NO:32和/或SEQ ID NO:33至少80％、至少85％、至少90％、至少95％、至少96％、至少97％、至少98％、至少99％相同的核苷酸序列编码；
(h)多肽序列，其是具有选自以下的氨基酸序列的P1-2A-P3多肽：SEQ ID NO：19、SEQID NO：21、SEQ ID NO：23、SEQ ID NO：25、SEQ ID NO：27、SEQ ID NO：29；
(i)多肽序列，其是具有与SEQ ID NO：19、SEQ ID NO：21、SEQ ID NO：23、SEQ ID NO：25、SEQ ID NO：27和/或SEQ ID NO：29至少80％、至少85％、至少90％、至少95％、至少96％、至少97％、至少98％、至少99％、至少99.1％、至少99.2％、至少99.3％、至少99.4％、至少99.5％、至少99.6％、至少99.7％、至少99.8％、至少99.9％相同的氨基酸序列的P1-2A-P3多肽。
9.一种抗体，其与权利要求8的多肽特异性结合。
10.一种免疫原性组合物，其包含：
(a)根据权利要求4至5中任一项的塞内卡病毒A(SVA)；和/或
(b)根据权利要求1至3中任一项的核酸；和/或
(c)根据权利要求8的多肽；和/或
(d)根据权利要求9的抗体；和/或
(e)根据权利要求8的多肽，其与异源或自体(多)肽融合；
以及任选地至少一种药学可接受的载体和/或赋形剂。
11.一种疫苗，优选重组疫苗或杀死的疫苗，其包含：
(a)根据权利要求4至5中任一项的塞内卡病毒A(SVA)；和/或
(b)根据权利要求1至3中任一项的核酸；和/或
(c)根据权利要求8的多肽；和/或
(d)根据权利要求9的抗体；和/或
(e)根据权利要求8的多肽，其与异源或自体(多)肽融合；
以及至少一种药学可接受的载体和/或赋形剂；任选地，所述疫苗进一步包含至少一种佐剂。
12.根据权利要求10的免疫原性组合物或根据权利要求11的疫苗，其用作药物，优选用于对象针对塞内卡病毒A(SVA)感染的预防和/或治疗的方法中，或用于在对象中引发针对塞内卡病毒A(SVA)感染的免疫应答的方法中，其包括向所述对象施用根据权利要求10的免疫原性组合物或根据权利要求11的疫苗的步骤，更优选地，所述对象是猪。
13.根据权利要求10的免疫原性组合物或根据权利要求11的疫苗，其用于减少对象中与塞内卡病毒A(SVA)感染相关或由塞内卡病毒A(SVA)感染引起的一种或多种临床体征的发生率或严重性的方法中，所述临床体征优选地选自：特发性水疱病，水疱病例如位于口鼻部、口腔粘膜和/或其中皮肤和蹄壁相交处(冠状带)的开放或闭合性水泡或病变，甲床出血，伴随在冠状带处或周围的发红和肿胀的突然/急性跛行；冠状带溃疡和蹄脱落；以及突然停止进食，嗜睡，厌食和/或发烧高达华氏105°(摄氏～40.6°)的繁殖雌性；更优选地，所述对象是猪。
14.一种试剂盒，其用于针对与塞内卡病毒A(SVA)感染相关的疾病给对象接种疫苗、和/或减少对象中与塞内卡病毒A(SVA)感染相关或由塞内卡病毒A(SVA)感染引起的一种或多种临床体征的发生率或严重性，所述试剂盒包括：
(a)能够向所述对象施用疫苗的分配器；和
(b)根据权利要求10或11的免疫原性组合物或疫苗，和
(c)任选的说明书手册；
优选地，所述对象是猪。
15.一种用于在样品中检测根据权利要求4或5的塞内卡病毒A(SVA)的方法，其包括以下步骤：
(i)使所述样品与对于根据权利要求1至3中任一项的核酸特异性的一种或多种寡核苷酸引物和/或探针接触，和
(ii)检测所述塞内卡病毒A(SVA)与所述一种或多种寡核苷酸引物和/或探针之间的结合；或
(iii)使所述样品与根据权利要求9的抗体接触，和
(iv)检测所述塞内卡病毒A(SVA)与所述抗体之间的结合；或
(v)检测所述样品中针对所述塞内卡病毒A的抗体(SVA)的存在或不存在。
16.一种用于诊断来自对象的样品中由根据权利要求4或5的塞内卡病毒A(SVA)的感染的方法，所述对象优选猪，所述方法包括根据权利要求15的用于检测所述塞内卡病毒A(SVA)的方法，其中所述塞内卡病毒A(SVA)的存在指示感染，或包括根据权利要求15的用于检测针对所述塞内卡病毒A(SVA)的抗体的方法，其中所述抗体的存在指示由所述塞内卡病毒A(SVA)的感染。
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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108531497A (zh) * 2016-12-26 2018-09-14 中国农业科学院兰州兽医研究所 一种重组蛋白p35的制备方法
CN111996202A (zh) * 2020-03-24 2020-11-27 中国农业科学院兰州兽医研究所 一种重组o型口蹄疫病毒vp1基因的塞内卡重组病毒、重组疫苗株及其制备方法和应用
CN112390861A (zh) * 2020-09-30 2021-02-23 信阳农林学院 表达猪塞内加谷病毒vp1蛋白的细胞系、构建方法和应用
CN112587660A (zh) * 2020-12-31 2021-04-02 中国农业科学院兰州兽医研究所 塞尼卡谷病毒3d蛋白作为免疫诱导剂或者佐剂的应用
CN113527516A (zh) * 2021-07-15 2021-10-22 中国农业科学院兰州兽医研究所 一种a型塞内卡病毒基因工程复合表位蛋白、疫苗及其应用
CN113908256A (zh) * 2021-11-26 2022-01-11 中国农业科学院兰州兽医研究所 Lancl1蛋白在制备抗病毒药物中的应用
CN116555141A (zh) * 2023-03-28 2023-08-08 青岛海华众康科技有限公司 一种表达猪塞内卡病毒重组蛋白的枯草芽孢杆菌及其应用

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021011619A1 (en) * 2019-07-15 2021-01-21 South Dakota Board Of Regents Senecavirus a virus strains and immunogenic compositions therefrom
CN111551747A (zh) * 2020-05-15 2020-08-18 金宇保灵生物药品有限公司 基于抗体检测用兔检验猪塞内卡病毒病灭活疫苗效力的方法
CN112294951B (zh) * 2020-11-09 2022-08-23 齐鲁动物保健品有限公司 一种猪塞内卡病毒疫苗及其制备方法
CN117487006B (zh) * 2023-12-29 2024-04-12 中国农业科学院哈尔滨兽医研究所（中国动物卫生与流行病学中心哈尔滨分中心） 一种抗a型塞内卡病毒的单克隆抗体以及抗原表位及应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006101841A2 (en) * 2005-03-23 2006-09-28 Neotropix, Inc. Seneca valley virus based compositions and methods for treating disease
US20070042002A1 (en) * 2005-08-16 2007-02-22 Hawaii Biotech, Inc. Influenza recombinant subunit vaccine
CN107073100A (zh) * 2014-09-23 2017-08-18 梅里亚股份有限公司 Fmdv重组疫苗及其用途

Family Cites Families (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US382425A (en) 1888-05-08 Brandt
US2909462A (en) 1955-12-08 1959-10-20 Bristol Myers Co Acrylic acid polymer laxative compositions
US4394448A (en) 1978-02-24 1983-07-19 Szoka Jr Francis C Method of inserting DNA into living cells
US4769331A (en) 1981-09-16 1988-09-06 University Patents, Inc. Recombinant methods and materials
US5505941A (en) 1981-12-24 1996-04-09 Health Research, Inc. Recombinant avipox virus and method to induce an immune response
US4722848A (en) 1982-12-08 1988-02-02 Health Research, Incorporated Method for immunizing animals with synthetically modified vaccinia virus
US5364773A (en) 1991-03-07 1994-11-15 Virogenetics Corporation Genetically engineered vaccine strain
US4769330A (en) 1981-12-24 1988-09-06 Health Research, Incorporated Modified vaccinia virus and methods for making and using the same
US5338683A (en) 1981-12-24 1994-08-16 Health Research Incorporated Vaccinia virus containing DNA sequences encoding herpesvirus glycoproteins
US4603112A (en) 1981-12-24 1986-07-29 Health Research, Incorporated Modified vaccinia virus
US5833975A (en) 1989-03-08 1998-11-10 Virogenetics Corporation Canarypox virus expressing cytokine and/or tumor-associated antigen DNA sequence
US5174993A (en) 1981-12-24 1992-12-29 Health Research Inc. Recombinant avipox virus and immunological use thereof
CA1247080A (en) 1983-03-08 1988-12-20 Commonwealth Serum Laboratories Commission Antigenically active amino acid sequences
US4745051A (en) 1983-05-27 1988-05-17 The Texas A&M University System Method for producing a recombinant baculovirus expression vector
US4945050A (en) 1984-11-13 1990-07-31 Cornell Research Foundation, Inc. Method for transporting substances into living cells and tissues and apparatus therefor
IL84154A0 (en) 1986-10-16 1988-03-31 Microgenesys Inc Polypeptides derived from the envelope gene of human immunodeficiency virus in recombinant baculovirus infected insect cells and vaccines against acquired immune deficiency syndrome containing the same
GB8717430D0 (en) 1987-07-23 1987-08-26 Celltech Ltd Recombinant dna product
WO1990001543A1 (fr) 1988-07-29 1990-02-22 Intracel Corporation Procede d'expression genetique de proteines heterologues par des cellules transfectees in vivo
CA2003300A1 (en) 1988-11-21 1990-05-21 Franklin Volvovitz Skin test and test kit for aids
DE69034078T2 (de) 1989-03-21 2004-04-01 Vical, Inc., San Diego Expression von exogenen Polynukleotidsequenzen in Wirbeltieren
US5703055A (en) 1989-03-21 1997-12-30 Wisconsin Alumni Research Foundation Generation of antibodies through lipid mediated DNA delivery
US5591439A (en) 1989-03-24 1997-01-07 The Wistar Institute Of Anatomy And Biology Recombinant cytomegalovirus vaccine
US5552143A (en) 1989-03-24 1996-09-03 The Wistar Institute Of Anatomy & Biology Recombinant cytomegalovirus vaccine
GB9001766D0 (en) 1990-01-25 1990-03-28 Univ Court Of The University O Vaccines
US5997878A (en) 1991-03-07 1999-12-07 Connaught Laboratories Recombinant poxvirus-cytomegalovirus, compositions and uses
KR100242671B1 (ko) 1991-03-07 2000-03-02 고돈 에릭 유전학적으로 처리한 백신 균주
US5643578A (en) 1992-03-23 1997-07-01 University Of Massachusetts Medical Center Immunization by inoculation of DNA transcription unit
US5846945A (en) 1993-02-16 1998-12-08 Onyx Pharmaceuticals, Inc. Cytopathic viruses for therapy and prophylaxis of neoplasia
IL108915A0 (en) 1993-03-18 1994-06-24 Merck & Co Inc Polynucleotide vaccine against influenza virus
FR2711670B1 (fr) 1993-10-22 1996-01-12 Pasteur Institut Vecteur nucléotidique, composition le contenant et vaccin pour l'immunisation à l'encontre d'une hépatite.
DE69536091D1 (de) 1994-01-27 2010-09-09 Univ Massachusetts Medical Immunisierung durch Impfung von DNS Transkriptionseinheit
CA2188447C (en) 1994-04-29 2002-10-22 Falko-Gunter Falkner Recombinant poxviruses with foreign polynucleotides in essential regions
AU711702B2 (en) 1995-03-23 1999-10-21 Cambridge University Technical Services Limited Vectors for gene delivery
WO1998000166A1 (en) 1996-07-03 1998-01-08 Merial, Inc. Recombinant canine adenovirus (cav) containing exogenous dna
US6183752B1 (en) 1997-02-05 2001-02-06 Pasteur Merieux Serums Et Vaccins Restenosis/atherosclerosis diagnosis, prophylaxis and therapy
WO2017181070A1 (en) * 2016-04-15 2017-10-19 Kansas State University Research Foundation Vaccine against seneca valley virus
CN107184969B (zh) 2017-04-18 2020-07-10 中农威特生物科技股份有限公司 一种a型赛尼卡谷病毒灭活疫苗及其制备方法和应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006101841A2 (en) * 2005-03-23 2006-09-28 Neotropix, Inc. Seneca valley virus based compositions and methods for treating disease
US20070042002A1 (en) * 2005-08-16 2007-02-22 Hawaii Biotech, Inc. Influenza recombinant subunit vaccine
CN107073100A (zh) * 2014-09-23 2017-08-18 梅里亚股份有限公司 Fmdv重组疫苗及其用途

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108531497A (zh) * 2016-12-26 2018-09-14 中国农业科学院兰州兽医研究所 一种重组蛋白p35的制备方法
CN111996202A (zh) * 2020-03-24 2020-11-27 中国农业科学院兰州兽医研究所 一种重组o型口蹄疫病毒vp1基因的塞内卡重组病毒、重组疫苗株及其制备方法和应用
CN111996202B (zh) * 2020-03-24 2021-09-10 中国农业科学院兰州兽医研究所 一种重组o型口蹄疫病毒vp1基因的塞内卡重组病毒、重组疫苗株及其制备方法和应用
CN112390861A (zh) * 2020-09-30 2021-02-23 信阳农林学院 表达猪塞内加谷病毒vp1蛋白的细胞系、构建方法和应用
CN112587660A (zh) * 2020-12-31 2021-04-02 中国农业科学院兰州兽医研究所 塞尼卡谷病毒3d蛋白作为免疫诱导剂或者佐剂的应用
CN112587660B (zh) * 2020-12-31 2022-07-22 中国农业科学院兰州兽医研究所 塞尼卡谷病毒3d蛋白在制备免疫应答诱导剂或者佐剂中的应用
CN113527516A (zh) * 2021-07-15 2021-10-22 中国农业科学院兰州兽医研究所 一种a型塞内卡病毒基因工程复合表位蛋白、疫苗及其应用
CN113908256A (zh) * 2021-11-26 2022-01-11 中国农业科学院兰州兽医研究所 Lancl1蛋白在制备抗病毒药物中的应用
CN116555141A (zh) * 2023-03-28 2023-08-08 青岛海华众康科技有限公司 一种表达猪塞内卡病毒重组蛋白的枯草芽孢杆菌及其应用
CN116555141B (zh) * 2023-03-28 2023-11-03 青岛海华众康科技有限公司 一种表达猪塞内卡病毒重组蛋白的枯草芽孢杆菌及其应用

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