CN110225765B - 减毒猪流感疫苗以及其制备和使用方法 - Google Patents

减毒猪流感疫苗以及其制备和使用方法 Download PDF

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CN110225765B
CN110225765B CN201780084468.5A CN201780084468A CN110225765B CN 110225765 B CN110225765 B CN 110225765B CN 201780084468 A CN201780084468 A CN 201780084468A CN 110225765 B CN110225765 B CN 110225765B
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T·梅巴特松
T·金
P·M·道尔
M·L·利布斯坦-贝利亚
A·T·里德
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Abstract

本公开内容提供了减毒猪流感毒株，特别是通过反求遗传学方法而产生的那些；包含其的组合物；以及其产生和使用方法。

Description

减毒猪流感疫苗以及其制备和使用方法
相关申请的交叉引用
本申请要求2016年11月30日提交的美国临时申请号62/428,062(其通过提及而以其整体合并入本文)的优先权。
通过提及的合并
任何先前的申请和所有在其中或在其审理期间所引用的文献(“申请引用文献”)和所有在所述申请所引用的文献中所引用或提及的文献，和所有在本文中所引用或提及的文献(“本文引用文献”)，和所有在本文引用文献中所引用或提及的文献，与关于任何在本文中或在任何通过提及而合并入本文的文献中所提到的产品的任何制造商的说明书、描述、产品规格书和产品说明页一起，特此通过提及而合并入本文，并且可以在本发明的实践中采用。在本申请中引用或鉴别任何这样的文献并不是承认此类文献可用作本发明的现有技术，并且不反映关于此类所引用的专利文献的有效性、可专利性和/或可行使性的任何观点。所有以GenBank登录号在本文中所提及的序列通过提及而以及整体合并入本文，并且所述序列如在GenBank中所示，截至本发明的提交日之时。
发明领域
总体而言，本发明涉及减毒病毒疫苗，特别是针对由猪流感病毒(SIV)引起的感染/疾病向猪提供广谱、安全且有效的保护作用的那些。本发明进一步涉及产生、测试和释放减毒病毒的方法，以及使用这些减毒SIV来在有此需要的猪类动物中引发保护性免疫的方法。
关于序列表的声明
与本申请相关的序列表以文本格式提供以替代纸质副本，并且特此通过提及而合并入说明书中。包含序列表的文本文件的名称为MER16-309p_ST25.txt。该文本文件为326KB；它创建于2016年8月16日；并且它通过EFS-Web以电子方式提交，与说明书的提交同时。
发明概述
流感病毒粒子包括包含单链RNA基因组的内部的核糖核蛋白核心(螺旋状核衣壳)，和由基质蛋白(M1)在里面铺衬的外部的脂蛋白包膜。甲型流感病毒的基因组由八个分节段的负义单链RNA分子组成。每个节段具有节段特异性RNA包装信号，其由在5′和3′末端这两者处的非编码区和短的编码区两者组成。所述八个分节段的RNA编码11个病毒蛋白质，包括RNA依赖性RNA聚合酶蛋白(PB2、PB1和PA)和核蛋白(NP)，其形成核衣壳；基质膜蛋白(M1、M2)；血凝素(HA)和神经氨酸酶(NA)，这两者都是从含脂质的包膜中突出的表面糖蛋白；非结构蛋白(NS1)、核输出蛋白(NEP，也称为NS2)、促凋亡因子PB1-F2。HA对于病毒结合和进入细胞来说是关键的，并且是主要的中和性抗体靶标；而NA在子代病毒释放中发挥作用并且对于病毒繁殖来说是必需的。该基因组的转录和复制发生在细胞核中，并且通过在质膜上出芽而发生装配。
猪流感(SI)是一种由甲型和丙型流感病毒引起的猪的急性呼吸系统疾病。猪也支持人和禽甲型流感病毒这两者的复制，并且已被假定在物种间传播中发挥重要作用，通过充当用于在特异于不同宿主的病毒之间的重排列的“混合容器”(Scholtissek,Eur.J.Epidemiol.(1994)10:455-458)。尽管有可用的疫苗，但是多种猪流感病毒(SIV)亚型继续在猪种群中循环。目前，H1N1、H3N2和H1N2是在北美猪种群中引起疾病的优势亚型。亚型H3N2的SIV通过在人、禽类和经典猪病毒之间的重排列而产生，正在经历快速进化，并且通常引起比经典的H1N1 SIV更严重的疾病。目前的SIV疫苗并不针对多种抗原性SIV变体提供保护。
一种用于产生新的流感疫苗株的方法是使所述基因中的一种或多种去优化，从而产生重组/重排列流感病毒，其不引起疾病，然而却引发针对随后的强毒SIV攻击的免疫学应答(参见例如，Research Foundation of the State University of New York的US2012/026,9849)。但是，并未尝试将该方法用于修饰猪流感病毒(SIV)以产生新型减毒SIV疫苗株。因此，仍然存在对于开发出用于治疗和预防猪流感感染的有效策略的需要。
本发明的一个目标是提供减毒猪流感病毒(SIV)，包含其的安全且有效的疫苗，以及用于治疗和预防由猪流感病毒(SIV)引起的感染和疾病的方法。
在一些实施方案中，所述疫苗包含减毒流感病毒，其已被修饰成包含去优化的编码序列，相对于它们所源自的相应的亲本毒株而言。在一个特别的实施方案中，所述安全且有效的SIV疫苗株携带密码子去优化的血凝素(HA-DO)、神经氨酸酶(NA-DO)和任选地非结构蛋白(NS-DO)基因编码序列。
本发明的另一个目标是提供cDNA和/或质粒，其用于在反求遗传学系统中使用，以用于产生根据本公开内容的减毒流感病毒。在一个实施方案中，所述cDNA和/或质粒包含与SEQ ID NO:22、29、35或105中所示的序列具有至少70％、至少80％或至少90％同一性的去优化的HA序列；与SEQ ID NO:25、32或38中所示的序列具有至少70％、至少80％或至少90％同一性的去优化的NA序列；和任选地，与SEQ ID NO:27中所示的序列具有至少70％、至少80％或至少90％同一性的去优化的NS序列。
通常，通过使用去优化的HA、NA和任选地NS1SIV编码序列来产生重排列SIV会产生出具有减弱的毒力的重排列体，当与所述HA、NA和任选地NS1序列所源自的强毒野生型毒株相比较时。
本发明进一步涉及新的减毒SIV毒株，其提供安全、有效且广谱的保护性(包括交叉保护性)免疫，相对于亲本H1N1、H1N2和H3N2 SIV毒株而言。
因此，本发明提供了突变型猪流感病毒，其相对于野生型/亲本病毒而言在一个或多个SIV HA、NA和任选地NS1核酸序列中包含沉默突变，这使得所述突变型/重排列病毒相对于亲本病毒而言是减毒的。在一些实施方案中，亲本SIV包含来自野生型H1N1、H1N2和H3N2 SIV毒株的SIV HA、NA和NS1核酸分子，每个序列包含野生型HA、NA和任选地NS1编码序列。在其他实施方案中，亲本SIV包含来自合成地或天然地减毒的H1N1、H1N2和H3N2 SIV毒株的SIV HA、NA和NS核酸分子，每个序列包含非野生型SIV HA、NA和任选地NS1编码序列。
因此，本发明的一个重要目标是提供减毒重排列SIV，其除了去优化形式的HA、NA和任选地NS1编码序列之外还包含一个由SIV内部基因构成的基本组。
因此，申请人在本文中首次公开，可以将不同的由去优化的HA、NA和任选地NS1编码序列构成的组与相同的由TRIG骨架H1N1 SIV M、NP、PA、PB1、PB2和任选地NS序列构成的核心组相组合，以产生安全且有效的重排列减毒SIV疫苗株。
本发明进一步提供了用于诱导针对流感的免疫学(或免疫原性)或保护性应答的方法，以及用于预防或治疗流感或由流感引起的疾病状态的方法，其包括向有此需要的动物施用所述减毒病毒或包含所述减毒病毒的组合物。
还提供了至少包含所述减毒流感毒株和使用说明书的试剂盒。
这些和其他实施方案通过下面的详细描述而公开，或者从下面的详细描述中而显而易见并且由下面的详细描述所包括。
附图简述
对于本领域普通技术人员来说本发明的完全且使成为可能的公开(包括其最佳方式)在说明书的其余部分中更具体地进行阐述，包括参考附图，其中：
图1为图，其显示了按组的总体的实变％(1＝vSIV01，2＝vSIV02，3＝vSIV05，4＝vSIV06，5＝对照)；
图2为表格，其描述了在本申请中所公开的序列；
图3A为pHW2000克隆载体的图谱，所述载体用于携带用于产生感染性的、重排列的、经反求遗传学产生的猪流感病毒(rgSIV)的基因区段；
图3B图解说明了pHW2000的构建，以合成的pHW2000克隆区域和pcDNA3.1/V5-HisB质粒为开始；
图4显示了HA区段(H1亚型)的3’UTR/信号序列和跨膜/尾区结构域/5’UTR的PCR扩增子；
图5呈现了包含HA区段(H1N2-DO)的3’UTR、信号序列(SS)、跨膜结构域(TMD)、胞质尾区结构域(CTD)和5’UTR的序列(SEQ ID NO:103)的图示图谱。
图6呈现了关于pHW2000-H1 SP-TM嵌合体的克隆规划方案；
图7为H3胞外结构域PCR扩增子的核苷酸序列(加有下划线的)；
图8显示了用于产生pHW2000-HA-DO(H1-H3嵌合体)的克隆规划方案；
图9呈现了pHW2000-HA-DO(H1-H3嵌合体)的核苷酸序列(SEQ ID NO:105)；
图10为图，其显示了攻击后组平均疫苗接种温度；
图11为图，其显示了按治疗组和对于在攻击后每一天所观察到的呼吸得分的发生率；
图12为图，其显示了按治疗组的和对于在攻击后每一天的总抑郁得分；
图13为图，其显示了按组和天的SIV ELISA结果；
图14为箱形图，其显示了攻击后肺损伤得分，如通过按组的总体的实变％所指出的。
发明详述
本发明提供了在微生物(例如，病毒，例如流感病毒)的减毒中所牵涉的核苷酸序列和基因；由所述核苷酸序列所编码的产物(例如，蛋白质、抗原、免疫原、表位)；用于产生此类核苷酸序列、产物、微生物的方法；以及其用途，例如用于制备疫苗或免疫原性组合物，或者用于引发免疫学或免疫应答，或者用作载体，例如用作表达载体(例如，体外或体内表达载体)。
被引入到微生物的核苷酸序列和基因中的突变产生新的且非显而易见的减毒突变体。这些突变体可用于产生具有高的免疫原性程度的活减毒免疫原性组合物或活减毒疫苗。
所述突变的鉴定提供了新的且非显而易见的核苷酸序列和基因，以及由所述核苷酸序列和基因所编码的新的且非显而易见的基因产物。
本发明部分地基于下述的引人注目的观察：用所公开的减毒SIV进行疫苗接种并然后用强毒H1N2 SIV进行攻击的猪具有相比于未疫苗接种的猪而言显著地降低的肺损伤和从呼吸道上的病毒脱落。由于用目前经批准的商业的灭活产物进行疫苗接种不完全阻止传播，所以团队建议引入新的控制策略，其涉及与另外的在猪中的控制措施相联合地来使用LAIV疫苗，以限制脱落、传播和人畜互传溢出(zoonotic spillover)。这样的策略将会使猪成为下一次大流行病的来源的风险最小化。
在一些实施方案中，本发明提供了用于评价减毒SIV降低疾病溢出/传播的能力的新的模型。在一些实施方案中，用再一种根据本公开内容的减毒SIV对动物进行疫苗接种。在经过了对于动物发展出保护性免疫来说足够的时间段后，可以用有效量的强毒SIV毒株攻击所述动物。典型地，所施用的攻击毒株的量足以使得技术人员能够确定，相对于对照/假经疫苗接种者而言，所述疫苗是否已在经疫苗接种者中引发了保护性免疫，包括异源保护性免疫。
一旦攻击了动物，就将它们放置在与岗哨动物邻近处，以评价疫苗接种保护岗哨动物对抗SIV传播的程度。在一些实施方案中，可以将经疫苗接种的动物和对照动物放置在与岗哨组足够紧密邻近处，从而使得如果所述动物脱落足够量的病毒，那么所述岗哨将会被暴露和被感染。每个经疫苗接种者和岗哨的组可以与另一个组在物理上相隔离，从而使得与一个经疫苗接种者组圈养一起的岗哨将不会被暴露于由另一个经疫苗接种者或对照组所脱落的攻击病毒。
在一个实施方案中，本发明提供了减毒猪流感病毒(SIV)毒株，其能够在猪中提供针对流感或由流感所引起的疾病的安全且有效的免疫应答。
在一些实施方案中，通过下述方式来产生去优化的序列：提供与SEQ ID NO:21、28或34中所示的序列具有至少70％、至少80％或至少90％序列同一性的野生型HA序列，与SEQID NO:24、31或37中所示的序列具有至少70％、至少80％或至少90％序列同一性的野生型NA序列，和任选地，与SEQ ID NO:1中所示的序列具有至少70％、至少80％或至少90％同一性的NS1序列。在一些实施方案中，这些野生型序列与野生型强毒H1N1、H1N2或H3N2 SIV毒株是同一的。
在一个特别的实施方案中，所述突变型病毒包含相应于(即，是反向互补的并且具有尿嘧啶而不是胸苷)SEQ ID NO:22、29、35或105(HA-DO)；SEQ ID NO:25、32或38(NA-DO)；和任选地，SEQ ID NO:27(NS1-DO)中所示的去优化的DNA序列的vRNA核酸序列，其造成所述突变型病毒相对于强毒野生型/亲本病毒而言是减毒的/非强毒的。
在一些实施方案中，SIV基因区段(即M、NP、PA、PB1、PB2和任选地NS)的余下部分包含野生型编码序列。在一个特别的实施方案中，所述野生型(即非去优化的)序列为H1N1SIV M、NP、PA、PB1、PB2和任选地NS序列。
在一些实施方案中，所述H1N1 NS1野生型编码序列包含与SEQ ID NO:1中所示的序列具有至少70％、至少80％或至少90％同一性的序列。在一些实施方案中，所述NS1野生型编码序列包含SEQ ID NO:1中所示的序列。
在一些实施方案中，所述H1N1 M1野生型编码序列包含与SEQ ID NO:3中所示的序列具有至少70％、至少80％或至少90％同一性的序列。在一些实施方案中，所述M1野生型编码序列包含SEQ ID NO:3中所示的序列。
在一些实施方案中，所述H1N1 M2野生型编码序列包含与SEQ ID NO:5中所示的序列具有至少70％、至少80％或至少90％同一性的序列。在一些实施方案中，所述M2野生型编码序列包含SEQ ID NO:5中所示的序列。
在一些实施方案中，所述H1N1 NP野生型编码序列包含与SEQ ID NO:9中所示的序列具有至少70％、至少80％或至少90％同一性的序列。在一些实施方案中，所述NP野生型编码序列包含SEQ ID NO:9中所示的序列。
在一些实施方案中，所述H1N1 PA野生型编码序列包含与SEQ ID NO:13中所示的序列具有至少70％、至少80％或至少90％同一性的序列。在一些实施方案中，所述PA野生型编码序列包含SEQ ID NO:13中所示的序列。
在一些实施方案中，所述H1N1 PB1野生型编码序列包含与SEQ ID NO:15中所示的序列具有至少70％、至少80％或至少90％同一性的序列。在一些实施方案中，所述PB1野生型编码序列包含SEQ ID NO:15中所示的序列。
在一些实施方案中，所述H1N1 PB2野生型编码序列包含与SEQ ID NO:17中所示的序列具有至少70％、至少80％或至少90％同一性的序列。在一些实施方案中，所述PB2野生型编码序列包含SEQ ID NO:17中所示的序列。
在另一些实施方案中，所述非去优化的编码序列也可以取自H1N2或H3N2 SIV毒株。例如，所述HA、NA和任选地NS1编码序列在去优化之前可以包含40、42、44、46、48、50、52、54、56、58、60、62、64、66、68、70、72、74或76中所示的序列。此外，基础毒株(即，“野生型”H1N1、H1N2或H3N2 SIV毒株)也可以本身是其更强毒的亲本毒株的合成地或天然地减毒的形式。
在另一个方面，本发明提供了包含上面所详述的减毒流感毒株的免疫学组合物。在一个实施方案中，所述组合物可以进一步包含在药学上或在兽医学上可接受的载料、稀释剂或赋形剂。
在一些实施方案中，所述免疫学组合物可以包括各种组分以改善其贮存稳定性。可以配制疫苗并通过使用例如加速稳定性研究来进行测试。在一些实施方案中，下面的成分组合可以用于产生根据本发明的稳定的疫苗制剂：
·蔗糖、磷酸盐缓冲液、谷氨酸、牛血清白蛋白
·大豆蛋白胨、右旋糖酐70、谷氨酸、蔗糖
·明胶、酪蛋白水解物、蔗糖
·右旋糖酐40、山梨醇、明胶、酪蛋白水解物、蔗糖。
因此，在一些实施方案中，合适的聚合物可以包括右旋糖酐40、右旋糖酐70、PEG、聚维酮或其组合。合适的动物蛋白质可以包括酪蛋白水解物、明胶、牛血清白蛋白(BSA)、乳白蛋白水解物，和非动物白蛋白可以包括大豆蛋白胨。合适的碳水化合物组分可以包括蔗糖、棉子糖、乳糖，和合适的缓冲液可以包括磷酸盐和组氨酸。一些有利的制剂组分包括PEG和聚维酮、乳白蛋白水解物、棉子糖和乳糖以及组氨酸。
在一些实施方案中，所述免疫学组合物可以包含下列稳定化组分中的任一种或所有：大约0.1％至大约2.5％的聚合物填充剂(例如，右旋糖酐、PEG、聚维酮等)、大约0.1％至大约4.5％的糖醇(例如，山梨醇、甘露醇等)、大约0.1％至大约2.5％的动物蛋白质(例如，酪蛋白水解物、明胶、BSA、LAH等)、大约0.1％至大约2.5％的植物蛋白质(例如，大豆蛋白胨等)、磷酸盐缓冲液、组氨酸缓冲液、大约1.0％至大约7.5％的碳水化合物(例如，乳糖、棉子糖、蔗糖、其组合等)。
在一些实施方案中，所述免疫学组合物可以包含下列组分，各自以该组合物的w/v(g/100mL)来表示：
·大约0.5％至大约1.0％的第一蛋白质类型，大约0.5％至大约1.0％的第二蛋白质类型，和大约2.0％至大约5.0％的非还原糖，
·大约0.5％至大约1.0％明胶，大约0.5％至大约1.0％酪蛋白水解物(CH)，和大约2.0％至大约5.0％蔗糖，
·大约1.0％至大约2.0％的聚合物，大约1.0％至大约2.0％的非动物来源的蛋白质，和大约0.25％至大约0.5％的谷氨酸盐，和大约2％至大约5％的非还原糖，
·大约1.0％至大约2.0％的右旋糖酐聚合物，大约1.0％至大约2.0％的大豆蛋白胨，和大约0.25％至大约0.5％L-谷氨酸一钾盐、大约2％至大约5％蔗糖，
·大约1.0％至大约2.0％的BSA，大约0.05％KH2PO4，大约0.14％K2HPO4，大约0.03％至大约0.1％的谷氨酸盐，和大约2％至大约5％蔗糖，
·大约1.2％至大约2.4％的右旋糖酐聚合物，大约1.2％至大约2.4％山梨醇，大约0.6％至大约1.2％CH，大约0.75％至大约1.5％明胶，大约0.015％至大约0.031％KH2PO4，大约0.0375％至大约0.075％K2HPO4，和大约2％至大约5％蔗糖。
在一个实施方案中，所述组合物在猪中提供针对强毒猪流感攻击的保护性免疫应答。保护可以是同源的、异源的或两者。在一些实施方案中，所述组合物进一步包含至少一种另外的与除了猪流感之外的其他病原体相关的抗原。
在另一个实施方案中，所述至少一种另外的抗原选自猪肺炎枝原体(Mycoplasmahyopneumoniae)(M.hyo)、PCV2、PRRSV、SIV或者其他能够在猪中进行感染和引起疾病或对疾病的易感性的病原体，或者其组合。
在一些实施方案中，组合包括三价的H1N1、H1N2、H3N2疫苗组合物。可以向年幼的猪施用此类组合物，例如通过鼻内途径。其他组合包括用于粘膜施用的以粉末制剂的一剂量MLV，用于在猪那边进行重构的多剂量小药囊包装规格，和密码子去优化的、M2基因阴性的SIV组合物。
在一个实施方案中，本发明提供了用于对动物进行疫苗接种的方法，其包括所述减毒SIV组合物的至少一次施用。在另一个实施方案中，所述猪为产仔前大约3周至大约6周的母猪或小母猪。在另外一个实施方案中，所得的猪仔可以具有相比于来自未疫苗接种的母猪的猪仔而言降低的发病率和/或死亡率。在其他实施方案中，待进行疫苗接种的动物为猪仔。所述猪仔可以是任何年龄的，包括大约1日龄至大约30日龄。在一些实施方案中，所述猪仔在大约1日龄和大约2至4周龄之间。
在一个实施方案中，本发明提供了用于制备流感病毒的方法，其包括使细胞与以对于产生感染性流感病毒来说有效的量的本发明的组合物之一相接触。所述方法进一步包括分离所述病毒。
在另一个实施方案中，本发明提供了用于制备基因递送载料的方法，其包括：使细胞与以对于产生流感病毒来说有效的量的本发明的组合物相接触，并且分离所述病毒。本发明进一步提供了与本发明的组合物相接触的细胞。
在一个实施方案中，本发明提供了脊椎动物细胞，其包含用于产生减毒猪流感病毒的多个载体，包括包含可操作地连接至流感病毒HA、NA和任选地NS1编码序列的启动子的载体，其中所述HA、NA和任选地NS1编码序列是密码子去优化的，相对于在强毒亲本SIV毒株中存在的非去优化的HA、NA和NS1编码序列而言。
本发明进一步包括基因产物，其提供抗原、免疫原和表位，并且作为分离的基因产物是有用的。
此类分离的基因产物，以及其表位，还可用于产生在诊断应用中有用的抗体。
此类基因产物(其可以提供或产生表位、抗原或免疫原)还可用于免疫原性或免疫学组合物，以及疫苗。
在一个方面，本发明提供了在核苷酸序列或基因中包含减毒性突变的病毒，其中所述突变修饰由基因所编码的多肽或蛋白质的生物学活性，从而导致所述病毒的减弱的毒力。
特别地，本发明包括减毒猪流感毒株以及包含其的疫苗，其在动物中引发免疫原性应答，特别是在猪中引发、诱导或刺激应答的减毒猪流感毒株。
相对于野生型强毒亲本毒株而言，特别的目的猪流感减毒株在与毒力相关的基因中具有突变。将会得到认可的是，除了具有所公开的突变的毒株之外，在本发明的实践中还可以使用在所公开的毒力基因中具有任何数目的突变的减毒株。
在另一个方面，将所述新型减毒重排列猪流感毒株配制成针对猪流感和由猪流感引起的感染/疾病的安全的、有效的疫苗。
在一个实施方案中，所述猪流感疫苗进一步包含佐剂。在一个特别的实施方案中，所述佐剂为粘膜佐剂，例如壳聚糖、甲基化壳聚糖、三甲基化壳聚糖或其衍生物，或者其组合。
在一个实施方案中，所述佐剂包含整个细菌和/或病毒，包括副猪嗜血菌(H.parasuis)、梭菌、猪流感病毒(SIV)、猪圆环病毒2(PCV2)、猪生殖和呼吸综合征病毒(PRRSV)、曼海姆氏菌属(Mannheimia)、巴斯德氏菌属(Pasteurella)、嗜组织菌属(Histophilus)、沙门氏菌属(Salmonella)、大肠杆菌(Escherichia coli)或者其组合和/或变化。在几个实施方案中，所述佐剂增加动物的IgM、IgG、IgA和/或其组合的产生。
在本文中所使用的术语“基因”将会以广义进行使用，并且应当包括编码序列和非编码序列(即，上游或下游调控序列、启动子、5’/3’UTR、内含子和外显子)两者。当想要提及仅基因的编码序列时，术语“基因的编码序列”或“CDS”将会在整个本公开内容中可互换使用。当讨论特定的核酸例如SEQ ID NO:17(亲本病毒cRNA“有义”链的等价DNA序列)中所示的序列时，技术人员将会立即拥有那个序列的所有可衍生形式(mRNA、vRNA、cRNA、DNA、蛋白质等)。例如，流感病毒为负的单链RNA病毒(ssRNA)。为了复制，它的负的ssRNA(在本文中定义为“vRNA”)必须转录为正的或有义的RNA(在本文中定义为“cRNA”)。接纳宿主细胞机器来使用所述cRNA去产生病毒蛋白质和vRNA。通过使用众所周知的遗传密码，技术人员可以从DNA序列常规地衍生出vRNA、cRNA和肽序列。
在本文中所使用的“野生型”意指，序列或毒株包含与当将它从自然界中分离出时它所是的那样相同的遗传序列。例如，已从被病毒感染的动物的细胞、组织或器官中回收的“野外分离物”是“野生型”病毒。在这些野外分离物内所述包含的基因区段包含野生型多核苷酸序列，其编码野生型多肽。“非野生型”毒株和序列为已经通过使用遗传工程技术或者通过在细胞、组织或器官中连续传代野生型或经修饰的病毒而被改变的那些。细胞传代是众所周知的用于产生减毒病毒的技术。
“抗原”或“免疫原”意指在宿主动物中诱导特异性免疫应答的物质。所述抗原可以包含整个生物(杀死的、减毒的或活的)；生物的亚基或部分；包含具有免疫原性特性的插入片段的重组载体；能够在呈递给宿主动物后诱导免疫应答的DNA的碎片或片段；多肽、表位、半抗原，或其任何组合。备选地，所述免疫原或抗原可以包含毒素或抗毒素。
术语“蛋白质”、“肽”、“多肽”和“多肽片段”在本文中可互换使用，以指任何长度的氨基酸残基的聚合物。所述聚合物可以是线性的或支化的，它可以包含经修饰的氨基酸或氨基酸类似物，并且它可以被除了氨基酸之外的其他化学部分所中断。该术语还包括已经天然地或通过干预而修饰了的氨基酸聚合物；例如，二硫键形成、糖基化、脂质化、乙酰化、磷酸化或任何其他操作或修饰，例如与标记组分或生物活性组分相缀合。
在本文中所使用的术语“免疫原性或抗原性多肽”包括这样的多肽，其在免疫学上有活性的，在一旦施用给宿主，它能够引起针对所述蛋白质的体液和/或细胞类型的免疫应答这一意义上。优选地，所述蛋白质片段是这样的，即它具有与全蛋白质基本上相同的免疫学活性。因此，根据本发明的蛋白质片段包含至少一个表位或抗原决定簇，或者基本上至少一个表位或抗原决定簇由组成，或者由至少一个表位或抗原决定簇组成。在本文中所使用的“免疫原性”蛋白质或多肽包括蛋白质的全长序列、其类似物或其免疫原性片段。“免疫原性片段”意指包括一个或多个表位并因此引发上面所描述的免疫学应答的蛋白质的片段。此类片段可以通过使用本领域中众所周知的许多表位作图技术来鉴定。参见例如，EpitopeMapping Protocols in Methods in Molecular Biology,第66卷(Glenn E.Morris,编辑,1996)。例如，线性表位可以通过下述方式来测定：例如，在固体支持物上同时合成大量的肽(所述肽相应于蛋白质分子的部分)，并且在所述肽仍然附着至所述支持物的同时使所述肽与抗体进行反应。此类技术是本领域中已知的，并且描述在例如美国专利号4,708,871；Geysen等人,1984；Geysen等人,1986中。类似地，构象表位通过测定氨基酸的空间构象(例如，通过x-射线晶体学和二维核磁共振)而容易地得到鉴定。参见例如，Epitope MappingProtocols,见上。尤其可应用于小泰勒虫(T.parva)的蛋白质的方法充分地描述在PCT/US2004/022605(其通过提及而以其整体合并入本文)中。
如在本文中所讨论的，本发明包括抗原性多肽的活性片段和变体。因此，术语“免疫原性或抗原性多肽”进一步考虑了对所述序列的缺失、添加和置换，只要所述多肽发挥功能而产生在本文中所定义的免疫学应答。术语“保守变化”表示氨基酸残基被另一个在生物学上相似的残基替代，或者在核酸序列中的核苷酸被替代，从而使得所编码的氨基酸残基不发生变化或者为另一个在生物学上相似的残基。在这方面，特别优选的置换通常将会是在自然界中保守的，即发生在氨基酸家族内的那些置换。例如，氨基酸通常被分成四个家族：(1)酸性的—天冬氨酸和谷氨酸；(2)碱性的—赖氨酸、精氨酸、组氨酸；(3)非极性的—丙氨酸、缬氨酸、亮氨酸、异亮氨酸、脯氨酸、苯丙氨酸、甲硫氨酸、色氨酸；和(4)不带电荷的极性的—甘氨酸、天冬酰胺、谷氨酰胺、胱氨酸、丝氨酸、苏氨酸、酪氨酸。苯丙氨酸、色氨酸和酪氨酸有时被归类为芳族氨基酸。保守性变化的例子包括一个疏水性残基例如异亮氨酸、缬氨酸、亮氨酸或甲硫氨酸被置换为另一个疏水性残基，或一个极性残基被置换为另一个极性残基，例如精氨酸置换为赖氨酸，谷氨酸置换为天冬氨酸，或谷氨酰胺置换为天冬酰胺，等等；或者氨基酸被在结构上相关的氨基酸的相似的保守替代，其对于生物学活性将不会具有重大影响。因此，与参考分子具有基本上相同的氨基酸序列但具有基本上不影响蛋白质的免疫原性的较少氨基酸置换的蛋白质在参考多肽的定义之内。所有由这些修饰所产生的多肽都包括在本文中。术语“保守变化”还包括使用经置换的氨基酸以代替未置换的亲本氨基酸，条件是对于所述经置换的多肽所引起的抗体也与所述未置换的多肽发生免疫反应。
术语“表位”是指特异性B细胞和/或T细胞对之作出应答的在抗原或半抗原上的位点。该术语也与“抗原决定簇”或“抗原决定簇位点”可互换使用。可以在显示出一种抗体阻断另一种抗体与靶抗原的结合的能力的简单免疫测定法中鉴定识别相同表位的抗体。
对于组合物或疫苗的“免疫学应答”是在宿主中发展出对于目的组合物或疫苗的细胞免疫应答和/或由抗体介导的免疫应答。通常，“免疫学应答”包括但不限于下列效应中的一种或多种：产生特异地针对在目的组合物或疫苗中所包括的抗原的抗体、B细胞、辅助T细胞和/或细胞毒性T细胞。优选地，所述宿主将会展示出治疗性或保护性免疫学应答，从而使得对于新的感染的抗性将会增强和/或疾病的临床严重度将会减小。这样的保护作用将会通过通常由被感染的宿主所展示出的症状和/或临床疾病征候的减少或缺乏、更快的恢复时间和/或在被感染的宿主中的降低的病毒滴度而得到证明。
“动物”意指哺乳动物、鸟类等。在本文中所使用的动物或宿主包括哺乳动物和人。所述动物可以选自由下列各项组成的组：马科动物(例如，马)、犬科动物(例如，狗、狼、狐狸、丛林狼、豺)、猫科动物(例如，狮子、老虎、家猫、野猫、其他大型猫类和其他猫科动物，包括猎豹和猞猁)、羊科动物(例如，绵羊)、牛科动物(例如，牛)、猪科动物(例如，猪)、鸟类(例如，鸡、鸭、鹅、火鸡、鹌鹑、雉、鹦鹉、雀类、鹰、乌鸦、鸵鸟、鸸鹋和食火鸡)、灵长类动物(例如，原猴亚目动物、眼镜猴、猴、长臂猿、猿)、白鼬、海豹和鱼类。术语“动物”还包括在所有发育阶段(包括新生、胚胎和胎儿阶段)中的个体动物。
除非另外解释，否则在本文中所使用的所有技术和科学术语具有与本公开内容所属领域中的普通技术人员通常所理解的相同的含义。单数术语“a”、“an”和“the”包括复数所指事物，除非上下文另有明确说明。类似地，词语“或”意在包括“和”，除非上下文另有明确说明。
应当注意的是，在本公开内容中和特别是在权利要求书和/或段落中，术语诸如“包含”可以具有在美国专利法中赋予它的含义；例如，它们可以意指“包括”；和术语诸如“基本上由……组成”具有在美国专利法中赋予它的含义，例如，它们允许未明确记述的要素，但排除在现有技术中发现的或影响本发明的基本或新颖特征的要素。
在本文中所使用的术语“大约”意指“近似地”、“在……的附近”、“大致地”或“……左右”。当术语“大约”与数值范围相联合地进行使用时，它通过扩展边界高于和低于所示的数值来修饰那个范围。通常，术语“大约”在本文中用于以10％的差异来修饰数值高于和低于所陈述的值。在一个方面，术语“大约”意指与它一起使用的数的数值的加或减20％。因此，大约50％意指在45％-55％的范围内。在本文中通过端点所记述的数值范围包括在那个范围内所包含的所有数和分数(例如，1至5包括1、1.5、2、2.75、3、3.90、4和5)。还应当理解的是，假定所有数和其分数通过术语“大约”来进行修饰。
组合物
本发明涉及可以包含减毒猪流感毒株和在药学上或在兽医学上可接受的承载体、赋形剂或载料的猪流感疫苗或组合物，其在动物中引发、诱导或刺激应答。
术语“核酸”和“多核苷酸”是指线性或支化的、单链或双链的RNA或DNA，或其杂合体。所述术语还包括RNA/DNA杂合体。下面为多核苷酸的非限制性例子：基因或基因片段、外显子、内含子、mRNA、tRNA、rRNA、核酶、cDNA、重组多核苷酸、支化的多核苷酸、质粒、载体、具有任何序列的分离的DNA、具有任何序列的分离的RNA、核酸探针和引物。多核苷酸可以包含经修饰的核苷酸，例如甲基化核苷酸和核苷酸类似物，尿嘧啶，其他糖和连接基团例如氟代核糖和硫代酯，和核苷酸分支。在聚合后，可以进一步修饰核苷酸的序列，例如通过与标记组分相缀合。在该定义中所包括的其他类型的修饰为帽，将天然出现的核苷酸中的一个或多个置换为类似物，和引入用于将所述多核苷酸附着至蛋白质、金属离子、标记组分、其他多核苷酸或固体支持物的工具。所述多核苷酸可以通过化学合成来获得或源自微生物。
术语“基因”广义地用于指任何与生物学功能相关的多核苷酸区段。因此，基因包括内含子和外显子(如在基因组序列中那样)，或者仅仅编码序列(如在cDNA中那样)和/或对于其表达来说所需要的调控序列。例如，基因也指表达mRNA或功能性RNA或者编码特定蛋白质的核酸片段，并且其包括调控序列。
“分离的”生物学组分(例如，核酸或蛋白质或细胞器)是指这样的组分，其已经与在所述组分天然地出现于之中的生物的细胞中的其他生物学组分(例如，其他染色体和染色体外DNA和RNA、蛋白质和细胞器)基本上分开或者从中纯化出来。已被“分离的”核酸和蛋白质包括通过标准纯化方法进行纯化的核酸和蛋白质。该术语还包括通过重组技术以及化学合成而制备的核酸和蛋白质。
术语“保守变化”表示氨基酸残基被另一个在生物学上相似的残基替代，或者在核酸序列中的核苷酸被替代，从而使得所编码的氨基酸残基不发生变化或者为另一个在生物学上相似的残基。在这方面，特别优选的置换通常将会是在自然界中保守的，如上面所描述的那样。
术语“重组(的)”意指具有半合成或合成起源的多核苷酸，其不出现在自然界中或者以在自然界中未发现的布置与另一个多核苷酸相连接。
“异源(的)”意指源自与将它与之进行比较的实体的其余部分在遗传上不同的实体。例如，多核苷酸可以通过遗传工程技术来放置到源自不同来源的质粒或载体中，并且是异源多核苷酸。从其天然编码序列移出并且可操作地连接至除了天然序列之外的其他编码序列的启动子是异源启动子。
本发明的多核苷酸可以包含另外的序列，例如在相同的转录单元内的另外的编码序列，控制元件例如启动子、核糖体结合位点、5’UTR、3’UTR、转录终止子、多腺苷酸化位点，在相同或不同启动子的控制之下的另外的转录单元，允许克隆、表达、同源重组和宿主细胞转化的序列，和任何诸如对于提供本发明的实施方案来说可能希望的这样的构建体。
使用方法和制品
本发明包括下列方法实施方案。在一个实施方案中，公开了对动物进行疫苗接种的方法，其包括向动物施用包含减毒猪流感毒株和在药学上或在兽医学上可接受的承载体、赋形剂或载料的组合物。在一个实施方案中，所述动物为猪类。
在本发明的一个实施方案中，可以采用初激-加强方案，其包括至少一次初次施用和至少一次加强施用，其中使用至少一种普通的多肽、抗原、表位或免疫原。典型地，在初次施用中所使用的免疫学组合物或疫苗在性质上不同于用作加强者的那些。但是，应当注意的是，相同的组合物可以用作初次施用和加强施用。该施用规程被称为“初激-加强”。
初激-加强方案包括至少一次初激施用和至少一次加强施用，其中使用至少一种普通的多肽和/或其变体或片段。在初激施用中所使用的疫苗可以在性质上不同于用作后来的加强疫苗的那些。所述初激施用可以包含一次或多次施用。类似地，所述加强施用可以包含一次或多次施用。
在一些实施方案中，所述初激疫苗接种可以用所公开的重排列减毒SIV疫苗制剂之一来进行。在这样的实施方案中，所述加强可以通过使用相同的减毒SIV疫苗制剂来进行，或者它可以通过使用不同的减毒SIV疫苗制剂来进行。在其他实施方案中，所述初激疫苗接种可以用自体疫苗(即，基于或源自目前在猪类动物种群中循环的毒株的疫苗)来进行。在这样的实施方案中，所述加强疫苗接种可以用相同的自体疫苗或者用在本文中所公开的减毒SIV疫苗制剂中的一种或多种来进行。由于已经公开了本发明，因而初激和加强的其他有效组合对于技术人员来说将会容易是明显的。
基于病毒抗原的用于为哺乳动物的靶物种的组合物的剂量体积，例如猪组合物的剂量体积，通常为大约0.1至大约2.0ml，大约0.1至大约1.0ml，和大约0.5ml至大约1.0ml。
疫苗的效力可以在最后一次免疫接种后大约2至4周通过用强毒猪流感毒株攻击动物例如猪来进行测试。使用同源和异源毒株两者用于进行攻击以测试疫苗的效力。可以通过IM或SC注射、喷雾、以鼻内方式、以眼内方式、以气管内方式和/或以口服方式来攻击动物。来自关节、肺、脑和/或口的样品可以在攻击之前和之后采集，并且可以就猪流感特异性抗体的存在来进行分析。
将在初激-加强规程中所使用的包含本发明的减毒病毒株的组合物包含于在药学上或在兽医学上可接受的载料、稀释剂或赋形剂中。本发明的规程保护动物免于猪流感和/或阻止在被感染的动物中的疾病进展。
各种实施方案优选地相隔1至6周来进行。在特别的实施方案中，所述时间间隔为大约3周至大约5周。在更特别的实施方案中，所述间隔为大约4周，并且也设想了一年一次的加强。猪类动物在首次施用之时可以为至少大约3-4周龄，或者它们可以甚至是1日龄那样年幼。
在一些实施方案中，所公开的减毒SIV疫苗制剂可以在每次妊娠期间进行施用。因此，在一些实施方案中，可以每年大约2次至3次(即，大约4次至大约6次/每年，在使用初激-加强疫苗接种方案的情况下)对母猪进行疫苗接种。对于母猪，特别有用的施用途径为肌内(IM)途径。
本领域技术人员应当理解，本文中的公开内容是作为实例来提供的，并且本发明并不局限于此。从本文中的公开内容和本领域中的知识之中，熟练技术人员可以确定施用次数、施用途径和待用于每次注射规程的剂量，而无需任何过度的实验。
本发明的另一个实施方案为用于施行在动物中引发或诱导针对猪流感的免疫学或保护性应答的方法的试剂盒，其包含减毒猪流感免疫学组合物或疫苗，和用于施行以对于在动物中引发免疫应答来说有效的量进行递送的方法的说明书。
本发明的另一个实施方案为用于施行在动物中诱导针对猪流感的免疫学或保护性应答的方法的试剂盒，其包含含有本发明的减毒猪流感毒株的组合物或疫苗，和用于施行以对于在动物中引发免疫应答来说有效的量进行递送的方法的说明书。
本发明的另外一个方面涉及用于上面所描述的根据本发明的初激-加强疫苗接种的试剂盒。所述试剂盒可以包含至少两个小瓶：包含用于根据本发明的初激疫苗接种的疫苗或组合物的第一小瓶，和包含用于根据本发明的加强疫苗接种的疫苗或组合物的第二小瓶。有利地，所述试剂盒可以包含用于另外的初激疫苗接种或另外的加强疫苗接种的另外的第一或第二小瓶。
在药学上或在兽医学上可接受的承载体或载料或赋形剂是本领域技术人员众所周知的。例如，在药学上或在兽医学上可接受的承载体或载料或赋形剂可以为0.9％NaCl(例如，盐水)溶液或磷酸盐缓冲液。可以用于本发明的方法的其他在药学上或在兽医学上可接受的承载体或载料或赋形剂包括但不限于：聚-(L-谷氨酸)或聚乙烯吡咯烷酮。所述在药学上或在兽医学上可接受的承载体或载料或赋形剂可以是有助于载体(或者在体外从本发明的载体中表达出的蛋白质)的施用的任何化合物或化合物的组合；有利地，所述承载体、载料或赋形剂可以有助于转染和/或改善载体(或蛋白质)的保存。剂量和剂量体积在本文中在一般性描述中进行了讨论，并且也可以由技术人员从本公开内容阅读中并结合本领域中的知识来确定，而无需任何过度的实验。
根据本发明的免疫学组合物和疫苗可以包含一种或多种佐剂或者基本上由一种或多种佐剂组成。用于在本发明的实践中使用的合适的佐剂为：(1)丙烯酸或甲基丙烯酸的聚合物、马来酸酐和链烯基衍生物聚合物；(2)免疫刺激序列(ISS)，例如具有一个或多个非甲基化CpG单元的寡脱氧核糖核苷酸序列(Klinman等人,1996；WO98/16247)；(3)水包油乳液，例如在由M.Powell,M.Newman发表的“Vaccine Design,The Subunit and AdjuvantApproach”(Plenum Press 1995)的第147页上所描述的SPT乳液，和在相同著作的第183页上所描述的乳液MF59；(4)包含季铵盐例如DDA的阳离子脂质；(5)细胞因子；(6)氢氧化铝或磷酸铝；(7)皂苷；或(8)在任何所引用并通过提及而合并入本申请中的文献之中所讨论的其他佐剂；或者(9)其任何组合或混合物。
在一个实施方案中，佐剂包括促进经改善的通过粘膜衬层的吸收的那些。一些例子包括MPL、LTK63、毒素、PLG微颗粒和几种其他的(Vajdy,M.Immunology and CellBiology(2004)82,617-627)。在一个实施方案中，所述佐剂可以为壳聚糖(Van der Lubben等人,2001；Patel等人,2005；Majithiya等人,2008；美国专利系列号5,980,912)。
在一些实施方案中，本发明提供了包含减毒猪流感病毒(SIV)的疫苗，所述减毒猪流感病毒毒株包含编码去优化的SIV血凝素(HA)基因，去优化的SIV神经氨酸酶(NA)基因，非去优化的SIV M、NP、PA、PB1和PB2基因，和任选地，去优化的SIV NS1基因的核酸分子；其中，正是相对于包含所述去优化的基因的野生型形式的相应的强毒亲本SIV毒株而言在SIV中所述去优化的基因的存在对于减毒表型负有责任。
在一些实施方案中，所述减毒SIV毒株包含去优化的SIV NS1基因。
在一些实施方案中，所述强毒亲本SIV毒株为天然SIV分离物。在一些实施方案中，所述强毒亲本毒株为H1N1、H1N2或H3N2毒株。
在一些实施方案中，所述去优化的HA基因包含具有SEQ ID NO:22、29或105中所示的序列的核酸分子；并且所述去优化的NA基因包含具有SEQ ID NO:25、32或38中所示的序列的核酸分子。
在一些实施方案中，所述去优化的HA和NA基因包含分别具有SEQ ID NO:22和25中所示的序列；分别具有SEQ ID NO:29和32中所示的序列；或者分别具有SEQ ID NO:105和38中所示的序列的核酸分子。
在一些实施方案中，所述去优化的NS1基因包含具有SEQ ID NO:27中所示的序列的核酸序列。
在一些实施方案中，所述非去优化的M、NP、PA、PB1和PB2为：
a)SIV H1N1基因，每个基因与SEQ ID NO:19(M)、9(NP)、13(PA)、15(PB1)和17(PB2)中所示的序列具有至少70％、至少80％或至少90％同一性；或
b)SIV H1N2基因，每个基因与SEQ ID NO:44(M)、48(NP)、52(PA)、54(PB1)和56(PB2)中所示的序列具有至少70％、至少80％或至少90％同一性；或
c)SIV H3N2基因，每个基因与SEQ ID NO:62(M1)、64(M2)、68(NP)、72(PA)、74(PB1)和76(PB2)中所示的序列具有至少70％、至少80％或至少90％同一性。
在一些实施方案中，所述非去优化的M、NP、PA、PB1和PB2为：
a)SIV H1N1基因，每个基因包含SEQ ID NO:19(M)、9(NP)、13(PA)、15(PB1)和17(PB2)中所示的序列；或
b)SIV H1N2基因，每个基因包含SEQ ID NO:44(M)、48(NP)、52(PA)、54(PB1)和56(PB2)中所示的序列；或
c)SIV H3N2基因，每个基因包含SEQ ID NO:62(M1)、64(M2)、68(NP)、72(PA)、74(PB1)和76(PB2)中所示的序列。
在另一个方面，本发明提供了用于在猪类动物中诱导保护性免疫应答的疫苗组合物，其包含一种或多种根据本公开内容的减毒猪流感病毒，其中所述保护性应答在疫苗接种后大约三(3)周内引发。
在一些实施方案中，所述疫苗组合物包含一种或多种减毒SIV，其包含至少一种编码去优化的SIV血凝素(HA)基因，去优化的SIV神经氨酸酶(NA)基因，非去优化的SIV M、NP、PA、PB1和PB2基因，和任选地，去优化的SIV NS1基因的核酸分子。在所述减毒SIV包含非去优化的NS基因的情况下，所述SIV也不包含去优化的NS1基因。
在一些实施方案中，正是相对于包含所述去优化的基因的野生型形式的相应的亲本SIV而言在重排列SIV中所述去优化的基因的存在对于减毒表型负有责任。在一些实施方案中，所述减毒SIV毒株包含去优化的SIV NS1基因、去优化的HA基因和去优化的NA基因区段，条件是其余的SIV基因区段是非去优化的。
在一些实施方案中，所述疫苗组合物进一步包含在药学上或在兽医学上可接受的载料、稀释剂或赋形剂。在一些实施方案中，所述疫苗在猪中提供针对强毒猪流感攻击的保护性免疫应答。在一些实施方案中，所述保护作用是同源的。在其他实施方案中，所述保护作用是同源的和异源的这两者。在另外其他实施方案中，疫苗包含多种亚型的减毒重排列SIV，并且在猪中引发针对强毒攻击和/或随后对强毒SIV H1N1、H1N2和H3N2亚型的暴露的保护性免疫应答。
在一些实施方案中，所述疫苗组合物进一步包含至少一种另外的与除了猪流感之外的其他猪病原体相关或者源自除了猪流感之外的其他猪病原体的抗原。
在一些实施方案中，所述至少一种或多种另外的抗原能够在猪中引发针对猪肺炎枝原体(M.hyo)、猪圆环病毒2(PCV2)、猪呼吸和生殖综合征病毒(PRRSV)或者其他能够在猪中进行感染和引起疾病或对疾病的易感性的病原体的免疫应答。
在另一个方面，本发明提供了在猪受试者中引发保护性免疫应答的方法，其包括向所述受试者施用预防或治疗有效剂量的所公开的疫苗组合物，其最少包含根据本公开内容的减毒SIV。
在一些实施方案中，所述方法进一步包括向所述受试者施用至少一种佐剂。
在另一个方面，本发明提供了对动物进行疫苗接种的方法，其包括至少根据本公开内容的疫苗组合物的至少一次施用。
在所述方法的一些实施方案中，所述猪为产仔前大约3周至大约6周的母猪。
在所述方法的一些实施方案中，所得的猪仔具有相比于来自未疫苗接种的母猪的猪仔而言降低的发病率和/或死亡率。
在另一个方面，本发明提供了疫苗产生性组合物，其包含多个用于产生减毒重排列猪流感病毒(SIV)的载体，包括包含可操作地连接至SIV HA、NA和任选地NS1cDNA的启动子的载体，其中所述HA、NA和任选地NS1cDNA编码去优化的编码序列，相对于相应的强毒SIV毒株的HA、NA和NS1编码序列而言。在本文中所使用的“疫苗产生性组合物”意指，当将所述组合物转染到合适的宿主细胞例如HEK细胞中时，将会产生重排列流感疫苗株。
在一些实施方案中，所述组合物包含质粒，所述质粒包含下列基因：去优化的HA和NA基因，其包含分别具有SEQ ID NO:22和25中所示的序列；分别具有SEQ ID NO:29和32中所示的序列；或者分别具有SEQ ID NO:105和38中所示的序列的核酸分子；和任选地，去优化的NS1基因，其包含具有SEQ ID NO:27中所示的序列的核酸序列。
在一些实施方案中，所述去优化的HA和NA基因包含分别具有SEQ ID NO:91和92中所示的序列；分别具有SEQ ID NO:93和94中所示的序列；或者分别具有SEQ ID NO:105和96中所示的序列的核酸分子；和任选地，所述去优化的NS1基因包含具有SEQ ID NO:90中所示的序列的核酸序列。
在一些实施方案中，所述载体包含下列TRIG基因区段：NS(SEQ ID NO:83)、M(SEQID NO:82)、NP(SEQ ID NO:81)、PA(SEQ ID NO:80)、PB1(SEQ ID NO:79)、PB2(SEQ ID NO:78)。
在一些实施方案中，所述载体包含下列TRIG基因区段：NS(SEQ ID NO:83)、M(SEQID NO:82)、NP(SEQ ID NO:81)、PA(SEQ ID NO:80)、PB1(SEQ ID NO:79)、PB2(SEQ ID NO:78)。
在一些实施方案中，所述质粒具有下列中所示的序列：a)SEQ ID NO:109和110；b)SEQ ID NO:108、109和110；c)SEQ ID NO:111和112；d)SEQ ID NO:108、111和112；e)SEQ IDNO:115和114；或f)SEQ ID NO:108、115和114。
在一些实施方案中，当将所述质粒转染到合适的病毒产生性细胞中时，产生选自vSIV01、vSIV02、vSIV03、vSIV04、vSIV05和vSIV06的减毒重排列病毒并且它们是可拯救的。
在另一个方面，本发明提供了制备流感病毒的方法，其包括使细胞与对于产生重排列的、减毒的、感染性的流感病毒来说有效的量的权利要求19至26中任一项的组合物相接触。
在另一个方面，本发明提供了细胞，其包含组合物，所述组合物包含所公开的多个编码SIV基因区段的反求遗传学载体。
在另外一个方面，本发明提供了二价减毒SIV疫苗，其包含有效量的减毒H1N1 SIV和有效量的减毒H3N2 SIV。
在一些实施方案中，所述二价减毒SIV疫苗包含有效量的减毒H1N2 SIV和有效量的减毒H3N2 SIV。
在一些实施方案中，本发明提供了三价减毒SIV疫苗，其包含有效量的减毒H1N1SIV、有效量的减毒H1N2和有效量的减毒H3N2 SIV。
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现在将通过下列非限制性实施例来进一步描述本发明。
实施例
实施例1–去优化的猪流感病毒的构建
材料/方法
简而言之，以三重重排列内部基因(TRIG)猪流感病毒(SIV)(A/猪/NorthCarolina/3793/08(H1N1))“基础基因组”为开始，通过使用标准的八质粒反求遗传学方法来产生重排列的经修饰的活的减毒(Modified Live Attenuated；MLV)流感病毒(LAIV)(Hoffman,2003；US 9,216,211(属于Merial,Inc.))。为了制备重排列LAIV，将TRIG序列添加至密码子去优化的HA(SEQ ID NO:22、29、35或105)、NA(SEQ ID NO:25、32或38)和NS(SEQID NO:27)。所述去优化的序列以下列基础序列为开始来产生：H1N1 HA(SEQ ID NO:21)、H1N2 HA(SEQ ID NO:28)和H3N2 HA(SEQ ID NO:34)；H1N1 NA(SEQ ID NO:24)、H1N2 NA(SEQ ID NO:31)和H3N2 NA(SEQ ID NO:37)。使基础CDS经历计算机辅助的密码子去优化，而不改变原始所编码的氨基酸。所述LAIV构建体的CDS内容概括在表1中。
表1.在vSIV01、vSIV02、vSIV05和vSIV06中存在的CDS
当将TRIG序列与来自野生型H1N1或野生型H1N2 SIV毒株的HA-DO、NA-DO和NS1-DO相组合时，回收到感染性重排列SIV病毒粒子。相反地，当将TRIG序列与来自H3N2 SIV毒株的HA-DO、NA-DO和NS1-DO相组合时，未回收到感染性重排列SIV病毒粒子。因此，申请人已经证明了广泛的原则，即来自H1N1或H1N2流感毒株(而不是一个特别的H3N2毒株)的HA、NA和NS1基因可以成功地与基于H1N1的TRIG基因相组合以产生减毒重排列SIV。
为了解决未预料到的问题，即源自H3N2的HA-DO、NA-DO和NS1-DO序列未成功地与TRIG序列相组合以产生感染性病毒粒子，申请人设计和构建了H3N2密码子去优化的HA基因的嵌合形式。简而言之，使野生型H3N2 HA(SEQ ID NO:34)和NA(SEQ ID NO:37)基因编码序列经历密码子去优化(Codagenix)以产生密码子去优化的H3N2 HA-DO(SEQ ID NO:35)和H3N2 NA-DO(SEQ ID NO:38)。所编码的氨基酸序列仍然是相同的，从而使得SEQ ID NO:34和35两者均编码SEQ ID NO:36中所示的氨基酸序列；并且SEQ ID NO:37和38两者均编码SEQ ID NO:39中所示的氨基酸序列。另外，使A/猪/NC/3793/2008(H1N1)的NS1基因的编码序列(SEQ ID NO:1)进行密码子去优化以产生NS1-DO(SEQ ID NO:27)。
将来自A/猪/North Carolina/3793/2008(H1N1)的六个内部基因区段克隆到pHW2000克隆载体(图3A)(SEQ ID NO:107)中，从而产生：pHW2000-PB2、pHW2000-PB1、pHW2000-PA、pHW2000-NP、pHW2000-M、pHW2000-NS。pHW2000本身通过下述方式来产生：合成双启动子-尾盒，pHW2000克隆区域，包括5’和3’EcoRV限制位点(参见Virology 267,310-317,2000，其通过提及而以其整体合并入本文)。然后，通过下述方式来从pCDNA3.1/V5-HisB中取出抗生素抗性基因盒和pUC起点：切割出HincII限制片段，并且将所述片段与包含双启动子的EcoRV片段连接在一起。所得的质粒为pHW2000，其构建图解说明在图3B中。
可以将多个质粒(各自包含双启动子盒(pCMV-tI-限制位点-pIh-BGH尾)和一个或多个流感病毒基因区段)转染到细胞中以产生感染性流感病毒颗粒(参见例如，US 2005/0186563A1，属于St.Jude Children’s Research Hospital，其也通过提及而以其整体合并入本文)。
由于已经公开了本发明的SIV重排列病毒的序列和组合，因而技术人员将会意识到，可以采用任何合适的反求遗传学系统来产生在本文中所公开的流感病毒颗粒。例如，可以表达所公开的去优化的和TRIG序列，以通过使用八质粒系统(US 6,951,754B2,，属于St.Jude)或单质粒系统(US 9,163,219B2，属于Arizona Board of Regents)(这两篇出版物均通过提及而以其整体合并入本文)来产生完整的感染性重排列病毒粒子。
完全的“TRIG”H1N1区段具有下列序列标号：PB2(SEQ ID NO:78)；PB1(SEQ ID NO:79)；PA(SEQ ID NO:80)；NP(SEQ ID NO:81)；M(SEQ ID NO:82)；NS(SEQ ID NO:83)。所述HA和NA具有下列序列标号：H1N1的HA(SEQ ID NO:84)；H1N1的NA(SEQ ID NO:85)；H1N2的HA(SEQ ID NO:86)；H1N2的NA(SEQ ID NO:87)；H3N2的HA(SEQ ID NO:88)；和H3N2的NA(SEQID NO:89)。
为了产生H3N2重排列SIV，化学合成了密码子去优化的H3N2 HA(HA-DO)(SEQ IDNO:95)和NA(NA-DO)(SEQ ID NO:96)基因区段(GenScript)，并且将其通过亚克隆来克隆到pHW2000中：pHW2000-H3N2-HA-DO(SEQ ID NO:113)；和pHW2000-H3N2-NA-DO(SEQ ID NO:114)。pHW2000-TRIG-NS-DO(SEQ ID NO:108)类似地进行构建，并且包含密码子去优化的NS1基因(SEQ ID NO:90)。
病毒拯救。按照制造商的规程，用Lipofectamine 2000CD(Invitrogen)来进行八(8)个反求遗传学质粒(其由来自TRIG(H1N1)的内部区段质粒(PB2、PB1、PA、NP、M、NS或NS-DO)和来自H3N2的密码子去优化的HA、NA区段组成)的共转染(表2和3)。但是，三次独立的转染/传代尝试没有成功地拯救感染性病毒。
表2.用于H3N2 HA、NA去优化的病毒的反求遗传学质粒
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO 95 14-3037 H3N2
5 NP 81 3793 H1N1
6 NA-DO 96 14-3037 H3N2
7 M 82 3793 H1N1
8 NS 83 3793 H1N1
表3.用于H3N2 HA、NA、NS去优化的病毒的反求遗传学质粒
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO 95 14-3037 H3N2
5 NP 81 3793 H1N1
6 NA-DO 96 14-3037 H3N2
7 M 82 3793 H1N1
8 NS-DO 90 3793 H1N1
用不同的NA区段进行转染。由于无法拯救去优化的H3N2病毒，因而使用密码子去优化的NA区段(H1N2 NA-DO；SEQ ID NO:94；来自A/猪/NC/0036-2/2010(H1N2))，以代替H3N2 NA-DO(表4和5)。H1N2-NA-DO支持用相同的规程来进行密码子去优化的H1N2病毒拯救(即，容易地回收具有HA-DO、NA-DO、NS1-DO的H1N2重排列病毒)。由于NA在SIV从细胞中的释放之中具有重要作用，因而申请人尝试通过使用H1N2-NA-DO来回收H3病毒。进一步地，该方法看起来是似乎有道理的，因为这两种NA都是N2亚型，并且具有大约92％氨基酸同一性。但是，没有H3/H1N2-NA-DO重排列病毒是可回收的。这表明，HA可能是问题所在，而不是NA。因此，设计和构建了嵌合HA区段。
表4.用H1N2 NA区段进行转染以用于密码子去优化的H3N2
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO 95 14-3037 H3N2
5 NP 81 3793 H1N1
6 NA-DO 94 0036-2 H1N2
7 M 82 3793 H1N1
8 NS 83 3793 H1N1
表5.用H1N2 NA区段进行转染以用于密码子去优化的H3N2
不幸地(和不可预知地)，通过使用密码子去优化的H1N2 NA区段(pHW2000-H1N2-NA-DO)，未实现感染性重排列病毒的拯救。因此，TRIG PB2、PB1、PA、NP、M、(NS)和H3N2HA-DO、(TRIG NS-DO)的组合不产生可拯救的量的感染性病毒。在产生重排列H3N2 SIV的进一步尝试中，使用不同的去优化的HA或NA区段的组合来检查H3N2 HA和NA区段与骨架质粒的相容性(表6和7)。然而，尽管进行了多次尝试，但还是未拯救到感染性病毒。
表6.用不同的HA区段进行转染以用于病毒拯救
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO 93 0036-2 H1N2
5 NP 81 3793 H1N1
6 NA-DO 96 14-3037 H3N2
7 M 82 3793 H1N1
8 NS 83 3793 H1N1
表7.用不同的NA区段进行转染以用于病毒拯救
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO 95 14-3037 H3N2
5 NP 81 3793 H1N1
6 NA-DO 92 14-0081 H1N1
7 M 82 3793 H1N1
8 NS 83 3793 H1N1
嵌合HA的构建。因为通过使用H3N2 HA-DO或H3N2 NA-DO无法拯救重排列SIV，所以构建了嵌合HA-DO区段，其中将H3N2的胞外结构域融合至H1N2 HA-DO蛋白(SEQ ID NO:86)的信号序列(SS)和跨膜结构域(TMD)/胞质尾区结构域(CTD)。因此，将编码HA(H3N2)的胞外结构域的多核苷酸序列克隆到包含H1N2 HA蛋白的SS、TMD和CTD的pHW2000(pHW2000-H1SP-TM)中。
pHW2000-H1 SP-TM的构建。用Bm-HA-F和3-Rev引物组通过PCR从pUC57-Kan-H1N2-HA-DO中扩增出HA区段的3’UTR/信号序列(表8，图4)。此外，还使用5-For和Bm-HA-R引物组通过PCR从pUC57-Kan-H1N2-HA-DO中扩增出HA区段的TMD、CTD和5’UTR(表8，图4)。两个PCR扩增子具有重叠序列(21nt，5’-GACACAATATGTGTAGGCTAC-3’)(SEQ ID NO:103)，其允许整个区域的扩增。使用两个PCR扩增子的混合物作为模板，以便用Bm-HA-正向和Bm-HA-反向引物组来扩增HA区段的3’UTR/SS/TMD/CTD/5’UTR(H1嵌合PCR扩增子)(图5)。
表8.用于构建pHW2000-H1 SP-TM的引物
pHW2000-H1 SP-TM的构建。通过BsmBI限制位点将H1嵌合PCR扩增子克隆到pHW2000中(图6)。
H3胞外结构域的PCR扩增和克隆到pHW2000-H1-SP-TM嵌合体中。通过使用H3ectFP(SEQ ID NO:101)和H3ectRP(SEQ ID NO:102)引物从pUC57-Kan-H3N2-HA-DO中扩增出HA(H3N2)的胞外结构域(图7)。接下来，通过NdeI和EcoRV限制位点将H3胞外结构域PCR扩增子(图7)克隆到pHW2000-H1 SP-TM嵌合体中(图8)。通过测序分析来确认所得的质粒的核苷酸序列(图9)。
H3N2病毒拯救。如上面所详述的和下面所概括的(表9、10和11)，用Lipofectamine2000CD进行反求遗传学质粒(包括内部区段质粒，pHW2000-HA-DO(H1-H3嵌合体)，和pHW2000-H3N2-NA-DO或pHW2000-H1N2-NA-DO、pHW2000-H1N1-NA-DO)的共转染。
表9.用于密码子去优化的HA-DO-H1-H3/H3N2 NA-DO病毒的反求遗传学质粒
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO-H1-H3 105 14-3037 H1N2-H3N2
5 NP 81 3793 H1N1
6 NA-DO 96 14-3037 H3N2
7 M 82 3793 H1N1
8 NS 83 3793 H1N1
表10.用于密码子去优化的HA-DO-H1-H3/H1N2 NA-DO病毒的反求遗传学质粒
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO-H1-H3 105 14-3037 H1N2-H3N2
5 NP 81 3793 H1N1
6 NA-DO 94 0036-2 H1N2
7 M 82 3793 H1N1
8 NS 83 3793 H1N1
表11.用于密码子去优化的HA-DO-H1-H3/H1N1 NA-DO病毒的反求遗传学质粒
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO-H1-H3 105 14-3037 H1N2-H3N2
5 NP 81 3793 H1N1
6 NA-DO 92 14-0081-1 H1N1
7 M 82 3793 H1N1
8 NS 83 3793 H1N1
从在HEK细胞中的转染和在MDCK细胞中的传代中回收了所有三种病毒。将所回收的具有密码子去优化的HA H1-H3嵌合体(SEQ ID NO:105)和密码子去优化的NA区段(H3N2)(SEQ ID NO:96)的病毒命名为vSIV03。另外，用相同的规程回收了具有去优化的HA和NA区段的去优化的NS区段病毒(表12和13)。
表12.用于密码子去优化的H3病毒的反求遗传学质粒
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO-H1-H3 105 14-3037 H1N2-H3N2
5 NP 81 3793 H1N1
6 NA-DO 96 14-3037 H3N2
7 M 82 3793 H1N1
8 NS-DO 90 3793 H1N1
表13.用于密码子去优化的H3病毒的反求遗传学质粒
区段 SEQ ID NO 毒株 亚型
1 PB2 78 3793 H1N1
2 PB1 79 3793 H1N1
3 PA 80 3793 H1N1
4 HA-DO-H1-H3 105 14-3037 H1N2-H3N2
5 NP 81 3793 H1N1
6 NA-DO 92 14-0081-1 H1N1
7 M 82 3793 H1N1
8 NS-DO 90 3793 H1N1
通过使用H1-H3嵌合HA区段，成功地回收并繁殖了具有密码子去优化的HA、NA区段或者密码子去优化的HA、NA、NS区段的感染性流感病毒。将所回收的具有密码子去优化的HAH1-H3嵌合体(SEQ ID NO:105)、密码子去优化的NA(SEQ ID NO:96)和密码子去优化的NS区段(SEQ ID NO:90)的病毒命名为vSIV04。
因此，将六(6)个由八(8)个基于pHW2000的反求遗传学质粒构成的组用于产生vSIV01、vSIV02、vSIV03、vSIV04、vSIV05和vSIV06，如在本文中所描述和测试的。表14概括了用于产生这些重排列SIV的基因区段。
表14.用于产生vSIV01、vSIV02、vSIV03、vSIV04、vSIV05和vSIV06的基因区段
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实施例2–在猪仔中减毒猪流感疫苗针对H1N2亚型攻击的保护效力
材料和方法。本研究包括五十只约克郡杂种猪，其由雌猪和经阉割的雄猪组成，它们经确认是SIV ELISA阴性的并且在第0天时为近似四周龄。猪仔来源于Midwest ResearchSwine,Princeton Sow群。所有猪都可以完全获取适合于其大小和年龄的商业丸粒化猪配给口粮，并且可以通过自动饮水机完全获取水供应。按治疗组将猪仔圈养在相同房间内的不同围栏中，没有鼻对鼻接触。
在第0天，用2mL(每个鼻孔1mL)的其各自的受试疫苗以鼻内方式(IN)对所有动物进行疫苗接种。在第21天，用2mL SIV H1N2亚型(每个鼻孔1mL)以鼻内方式攻击所有动物。当操作和施用实验产品时，遵循适当的预防措施、技术和安全惯例。从猪中采集血液以用于在为了筛选目的的研究开始之前和在第0、21和26天时进行血清滴度分析。在第1、7、22、24和26天时从猪中采集鼻拭子，并将其用于通过qRT-PCR来检测病毒复制。在第21(攻击前)至26天时，从猪中采集直肠体温。从第-7天至第26天进行并记录每日一般健康观察(DailyGeneral Health Observation)。从第22天至第26天进行并记录攻击后临床观察。由对治疗分配不知情的兽医就病理学对所有肺进行目视评估，其中估计每个肺叶的实变/肺部累及百分比，如从下述公式推导出的并记录在原始数据中的。
总体的实变百分比＝[(％LA*0.05)+(％LC*0.06)+(％LD*0.29)+(％RA*0.11)+(％RC*0.10)+(％RD*0.34)+(％I*0.05)]*100
将每个肺的右中叶的样品在10％福尔马林中进行固定，并且就免疫组织化学(IHC)得分进行评估。此外还将每个肺的相似切片保持新鲜并通过RT-PCR测试来进行分析。
表15.实验性疫苗细节(“DO”＝去优化的序列)；PBS阴性对照；以6.0log10TCID50/mL用SIV 10-0036-1 051515(H1N2)进行攻击
表16.研究组
结果。图1显示了箱形图，其显示了按组的总体的实变％。为了获得关于肺组织的发生率评估的目的，将具有≥10％的肺组织得分百分比的猪仔划归为阳性，和将具有<10％的肺组织得分百分比的猪仔划归为阴性。重要的是，相比于PBS对照而言，包含去优化的HA(HA-DO)和去优化的NA(NA-DO)基因的rgSIV(组1、2、3和4)提供了显著的对于肺损伤的保护作用。
此外，包含HA-DO、NA-DO和NS1-DO的rgSIV(组2和4)显示出超过仅具有其去优化的HA和NA基因的其相应的rgSIV(分别为组1和3)的增强的保护作用的趋势。还重要的是注意，由于攻击毒株为强毒H1N2，因而基本上就其引发同源保护作用的能力来评价施用给组1和2的rgSIV，而基本上就其引发异源保护作用的能力来评价施用给组3和4的rgSIV。这至少部分地解释了，为什么当与在组5的动物(即，对照组)中所引发的保护作用相比较时，在组3和4的动物中所引发的保护作用是显著的，但不像在组1和2的动物中所引发的保护作用那样强。
申请人设想，可以在本发明的实践中采用去优化的HA、NA和/或NS1的许多不同组合。例如，如果希望对于H1N2的保护作用，那么可以将去优化的HA、NA和NS1添加至其他五个TRIG区段(或甚至添加至另一SIV骨架毒株，如所希望的)，以产生高度有效的减毒的H1N2去优化的rgSIV。
表17.阳性肺组织得分的发生率
表18：病毒载量
表19.按组的阳性PCR结果的发生率
表20.关于经疫苗接种的组与安慰剂组的PCR结果的比较，发生率汇总统计、Wilcoxon检验的p-值和减轻分数(Mitigated Fraction)
表21.按天和组的SIV血清学的最小二乘方平均值(LSM)
结论。对于所有治疗组，攻击后的肺损伤得分显著更低。组vSIV01和vSIV02帮助阻止肺损伤，而组vSIV05和vSIV06帮助控制肺损伤。对于vSIV01和vSIV02，减轻分数为100％，这证明了对于同源攻击的完全保护作用。有希望的是，vSIV05和vSIV06的减轻分数分别为70％和82％，这显示了针对异源攻击的对于肺损伤的显著的交叉保护作用水平。鉴于在申请人发展出所公开的发明之时的技术了解状态，这样的水平是不可预测的。最后，没有观察到异常的疫苗接种后反应，包括抑郁和过敏症。
实施例3–在猪仔中减毒猪流感疫苗针对H1N1或H3N2亚型攻击的保护效力
一般而言，本研究通过使用在实施例2中所描述的方法来进行，除非另外说明(细节概括在表22中)。简而言之，通过使用一胎猪仔作为随机化因素，将猪仔分派至六个(6)治疗组中的一个。在疫苗接种后但在攻击前，将在组1、2、4和5中的猪仔圈养在与对照隔开的分开的房间中(所有经疫苗接种者在一个/两个房间中)。来自不同的经疫苗接种者组的猪没有鼻对鼻接触。但是，在攻击前，将组1和4圈养在一起。
在攻击前，在第21天，合并被分配至组1、2和3的猪仔并将其圈养在一起，和合并被分配至组4、5和6的猪仔并将其圈养在一起，直至研究结束。
表22.研究设计
鉴于通过在实施例2中呈现的结果所证明的保护效力，预期组1、2、4和5的疫苗将会引发比各自的对照疫苗(3和6)显著地更大的保护性免疫。
结果。图14显示了箱形图，其显示了按组的总体的实变％。
表23.关于经疫苗接种者组与对照组的总体的实变百分比的比较，Wilcoxon检验的P-值和减轻分数
表24.关于经疫苗接种者组与对照组的显微肺IAV损伤的比较，Wilcoxon检验的P-值和减轻分数
表25.关于经疫苗接种者组与对照组的肺IAV IHC得分的比较，Wilcoxon检验的P-值和减轻分数
表26.关于经疫苗接种者组与对照组的在攻击后在鼻道中的病毒载量的发生率的比较，费希尔精确检验的P值和阻止分数(Prevented Fraction)
结论。当与对照组相比较时，对于单价疫苗和三价疫苗两者均关于总肺损伤观察到显著的疫苗效应。对于显微损伤也是如此，除了组4(三价的/H3N2攻击)外，其未显示显著的下降。得分在该组中相比于对照组而言更低并且可能是选择偏倚的产物，但是该观察结果与在下面所描述在相同组中所观察到的IHC得分相一致。
关于肺移殖建群，当与用H1N1进行攻击的对照组相比较时，用组1和2观察到显著的疫苗效应。当与用H3N2进行攻击的对照相比较时，在组4和5中未观察到疫苗效应。关于鼻脱落，在所有经疫苗接种的组中都观察到显著的疫苗效应，其防止脱落，当与对照相比较时。对于接受H1N1攻击的组，在6个观察日中的4个之中，临床呼吸特征在经疫苗接种者中比对照低。对于接受H3N2攻击的那些组，在6个观察日中的2个之中，临床呼吸特征在经疫苗接种者中更低。当与对照相比较时，在接受H1N1攻击的经疫苗接种者中抑郁得分更低，但是对于接受H3N2攻击的那些，在非常少的猪中观察到抑郁并因此无法充分地对其进行评估。当与对照相比较时，攻击后的温度在所有经疫苗接种的组中是更低的。最后，没有观察到异常的疫苗接种后反应，包括抑郁和过敏症。
实施例4–用于评价疫苗接种对于攻击病毒传播的效应的岗哨模型的开发和实施
一般而言，本研究通过使用在实施例3中所描述的方法来进行，其中加入了阳性对照岗哨动物合并，除非另外说明(细节概括在表27中)。
为了评价实际的病毒传播，而不是仅仅测量病毒脱落(例如，通过鼻拭子和病毒检测)，有必要开发出岗哨模型。申请人料想，无法肯定地预测通过在攻击后立即还是在攻击后某时合并对照和经疫苗接种的动物与岗哨将会产生最佳条件。由于了解峰值SIV脱落通常在暴露于强毒攻击SIV毒株后大约48小时之时出现，因而申请人推论开始进行合并的好时间将会是大约12小时至大约36小时。对于本研究选择了24小时延迟。该在合并方面的延迟将会允许攻击病毒有足够的时间被吸收并分散入圈养环境中。备选地，可以在攻击后立即合并动物。
表27.研究设计–岗哨模型条件
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疫苗被证明在下列情况下减少传播：
(a)合并的组1和2
由于申请人已经开发出了该方法，因而可以就其减少攻击病毒传播的能力来测试任何数目的疫苗。在岗哨模型研究设计与实施例2和3中所公开的研究设计之间的重要差异为包括了阳性对照组(即，对于每种疫苗，每个空间/圈养环境存在2个组)。该特征，与延迟在攻击和合并之间的时间这一选择一起，允许岗哨模型测量任何SIV疫苗对于病毒传播的影响。
实施例5–经修饰的活疫苗的遗传稳定性
目标。为了评价在与野生型病毒一起在体内共接种后经修饰的活疫苗的遗传稳定性，并且评估在使用IAV疫苗的猪中VAERD的潜在出现。表28呈现了总体研究设计。
主要变量。评价了下列各项：1)在共接种的疫苗和攻击病毒的体内传代后所回收的疫苗病毒的密码子去优化的HA、NA和NS1基因的遗传稳定性；2)疫苗相关的增强型呼吸系统疾病(Vaccine Associated Enhanced Respiratory Disease；VAERD)，基于在体内传代后来自接受了MLV IAV疫苗的猪的肺损伤和病毒脱落的评估；和3)受试疫苗的效力。
疫苗接种和攻击。在第0天和在第21天，猪仔在右鼻孔中接受2个剂量的疫苗。在第21天，所有猪仔在左鼻孔中接受一定剂量的合适的攻击材料。
每日临床观察：就一般健康状态和IAV疾病的征候(发热、昏睡、呼吸困难)每日观察所有猪仔。
表28.研究设计
组 动物数目 疫苗接种 途径 频率 剂量体积 攻击
1 10 H1N1 IN 第0和21天 1mL H1N1
2 10 H1N2 IN 第0和21天 1mL H1N1
3 10 安慰剂 IN 第0和21天 1mL H1N1
4 10 H3N2 IN 第0和21天 1mL H3N2
5 10 Placebo IN 第0和21天 1mL H3N2
实施例6–经修饰的活疫苗的体外遗传稳定性
将疫苗在ST细胞中连续传代，并且如在表29中所指出的，vSIV01、02、05和06保持相当稳定。
表29.序列分析表明，vSIV在ST细胞中进行10次传代后保持稳定
基因 vSIV01 vSIV02 vSIV05 vSIV06
HA 无变化 无变化 无变化 1nt/aa
NA 无变化 无变化 无变化 无变化
NS 无变化 无变化 无变化 无变化
实施例7–配制成精细研磨粉末的疫苗
在犬细胞系MDCK上产生三种主种子病毒(Master Seed Viruse；MSV)，即SIV02(H1N2)、SIV 04(H3N2)和SIV06(H1N1)。将病毒与稳定化组分相组合，并且使用以前所描述的技术进行冻干和/或玻璃化(参见例如US 2013/0040370和US 2016/0256554，两者都属于Merial,Inc.)。然后，使经干燥的生物学材料经历碾磨以产生精细研磨粉末。就随时间的稳定性来对所述粉末进行检定。
表30.配制成粉末的单价SIV04(H3N2)的稳定性
表31.配制成粉末的三价
SIV02(H1N2)SIV04(H3N2)SIV06(H1N1)的稳定性
因此，当配制成干燥的精细研磨粉末时，本发明的免疫学组合物是稳定的。
＊＊＊＊＊＊＊＊
由于已经如此详细地描述了本发明的优选实施方案，应当理解的是，通过上述段落所定义的本发明并不局限于在上面描述中所示的具体细节，因为其许多明显的变化是可能的，而不背离本发明的精神或范围。
序列表
<110> Merial, Inc.
Mebatsion, Teshome
Kim, Taejoong
Dorr, Paul
Liebstein, Martin
Alton Timothy Leard
<120> 减毒猪流感疫苗以及其制备和使用方法
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Trp Ile Ser His Ser Ile Gln Thr Glu Gly Lys Asn His Thr Glu Met
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gattccaata ccttagagct gagaagcaga tactgggcta taaggaccag aagtggagga 1200
aatactaatc aacagaaagc atccgcaggc cagatcagtg tgcaacctac attctcagtg 1260
caacggaatc tcccttttga aagagcaacc gttatggcag ctttcagcgg aaacaatgaa 1320
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Thr Leu Pro Arg Arg Ser Gly Ala Ala Gly Ala Ala Val Lys Gly Val
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Gln Arg Ala Met Met Asp Gln Val Arg Glu Ser Arg Asn Pro Gly Asn
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Arg Gly Ser Val Ala His Lys Ser Cys Leu Pro Ala Cys Val Tyr Gly
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305 310 315 320
Leu Val Arg Pro Asn Glu Asn Pro Ala His Lys Ser Gln Leu Val Trp
325 330 335
Met Ala Cys His Ser Ala Ala Phe Glu Asp Leu Arg Val Ser Ser Phe
340 345 350
Ile Arg Gly Lys Lys Val Ile Pro Arg Gly Lys Leu Ser Thr Arg Gly
355 360 365
Val Gln Ile Ala Ser Asn Glu Asn Val Glu Ala Met Asp Ser Asn Thr
370 375 380
Leu Glu Leu Arg Ser Arg Tyr Trp Ala Ile Arg Thr Arg Ser Gly Gly
385 390 395 400
Asn Thr Asn Gln Gln Lys Ala Ser Ala Gly Gln Ile Ser Val Gln Pro
405 410 415
Thr Phe Ser Val Gln Arg Asn Leu Pro Phe Glu Arg Ala Thr Val Met
420 425 430
Ala Ala Phe Ser Gly Asn Asn Glu Gly Arg Thr Ser Asp Met Arg Thr
435 440 445
Glu Ile Ile Arg Met Met Glu Asn Ala Lys Pro Glu Asp Leu Ser Phe
450 455 460
Gln Gly Arg Gly Val Phe Glu Leu Ser Asp Glu Lys Ala Thr Ser Pro
465 470 475 480
Ile Val Pro Ser Phe Asp Met Ser Asn Glu Gly Ser Tyr Phe Phe Gly
485 490 495
Asp Asn Ala Glu Glu Tyr Asp Ser
500
<210> 11
<211> 1698
<212> DNA
<213> 猪流感病毒
<400> 11
atgaaggcaa tactagtagt cctgctatat acatttacaa ccgcaaatgc cgacacatta 60
tgcataggtt atcatgcgaa caattcaact gacaccgtag acacagtgct agaaaaaaat 120
gtaacagtaa cacactctgt caaccttcta gaaaacaggc ataatgggaa actatgtaaa 180
ctaagagggg tagctccatt gcatttgggt aaatgtaaca ttgctggctg gctcctggga 240
aatccagagt gtgagtcaat ctccaaagca agctcatggt cctacattgt ggaaacatct 300
aattcagaca atgggacgtg ttacccagga gatttcatca attatgagga gctaagagag 360
cagttgagct cagtgtcatc atttgaaaga tttgagatat tccccatgac aagttcatgg 420
cccaatcatg acacgaacag aggtgtgacg gcagcatgtc ctcacgctgg gacaaatagc 480
ttctacaaaa atttaatatg gctggtcaaa aaaggaaatt catacccaaa gatcaacaaa 540
tcctacatta acaacaaaga gaaagaagtt ctcgtgctat gggccataca tcatccacct 600
accaatgccg accaacaaag cctctaccaa aatgcagatg cctatgtttt tgtggggtca 660
tcaagataca gcaggaagtt cgagccagaa atagcaacaa gacccaaggt gagagaccaa 720
gcagggagaa tgaactatta ctggacattg gtagagcctg gagacaagat aacattcgaa 780
gcaactggaa atctagtggt accgagatat gccttcgcat tgaaaagaaa ttctggatct 840
ggtattatca tttcagatac atcagtccac gattgtgata cgacttgtca gacacccaat 900
ggtgctataa acaccagcct cccatttcaa aatatacatc cagtcacaat tggagaatgt 960
ccaaaatatg taaaaagtac taaactgaga atggccacag gattaaggaa tatcccgtct 1020
attcaatcta gaggcctgtt tggggccatt gctggcttta ttgaaggggg ctggacagga 1080
atgatagacg gatggtacgg ttaccaccat caaaatgagc agggatcagg atatgcagcc 1140
gacctgaaaa gcacacagaa tgccattgac gggatcacta acaaggtaaa ttctgttatt 1200
gaaaagatga acacacaatt cacagcagta ggtaaagagt tcagccactt ggaaagaaga 1260
atagagaatt taaataaaaa ggttgatgat ggttttctag atatttggac ttacaatgcc 1320
gaactgttgg ttctgttgga gaatgaaaga actttggatt accacgattc aaatgtgaaa 1380
aacttatatg aaaaagtaag aagccaacta aaaaacaatg ccaaagaaat tggaaatggc 1440
tgctttgaat tttaccacaa atgtgatgac acgtgtatgg aaagcgtcaa aaatgggact 1500
tatgattacc caaaatactc agaggaagca aaactaaaca gagaggaaat agatggggta 1560
aagttggaat caacaagggt ttaccaaatt ttggcgatct attcaacggt cgccagttca 1620
ttggtactgg tagtctccct gggggcaatc agtttctgga tgtgctctaa tgggtcgcta 1680
cagtgcagaa tatgtatt 1698
<210> 12
<211> 566
<212> PRT
<213> 猪流感病毒
<400> 12
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Thr Thr Ala Asn
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Leu Glu Asn Arg His Asn Gly Lys Leu Cys Lys Leu Arg Gly Val
50 55 60
Ala Pro Leu His Leu Gly Lys Cys Asn Ile Ala Gly Trp Leu Leu Gly
65 70 75 80
Asn Pro Glu Cys Glu Ser Ile Ser Lys Ala Ser Ser Trp Ser Tyr Ile
85 90 95
Val Glu Thr Ser Asn Ser Asp Asn Gly Thr Cys Tyr Pro Gly Asp Phe
100 105 110
Ile Asn Tyr Glu Glu Leu Arg Glu Gln Leu Ser Ser Val Ser Ser Phe
115 120 125
Glu Arg Phe Glu Ile Phe Pro Met Thr Ser Ser Trp Pro Asn His Asp
130 135 140
Thr Asn Arg Gly Val Thr Ala Ala Cys Pro His Ala Gly Thr Asn Ser
145 150 155 160
Phe Tyr Lys Asn Leu Ile Trp Leu Val Lys Lys Gly Asn Ser Tyr Pro
165 170 175
Lys Ile Asn Lys Ser Tyr Ile Asn Asn Lys Glu Lys Glu Val Leu Val
180 185 190
Leu Trp Ala Ile His His Pro Pro Thr Asn Ala Asp Gln Gln Ser Leu
195 200 205
Tyr Gln Asn Ala Asp Ala Tyr Val Phe Val Gly Ser Ser Arg Tyr Ser
210 215 220
Arg Lys Phe Glu Pro Glu Ile Ala Thr Arg Pro Lys Val Arg Asp Gln
225 230 235 240
Ala Gly Arg Met Asn Tyr Tyr Trp Thr Leu Val Glu Pro Gly Asp Lys
245 250 255
Ile Thr Phe Glu Ala Thr Gly Asn Leu Val Val Pro Arg Tyr Ala Phe
260 265 270
Ala Leu Lys Arg Asn Ser Gly Ser Gly Ile Ile Ile Ser Asp Thr Ser
275 280 285
Val His Asp Cys Asp Thr Thr Cys Gln Thr Pro Asn Gly Ala Ile Asn
290 295 300
Thr Ser Leu Pro Phe Gln Asn Ile His Pro Val Thr Ile Gly Glu Cys
305 310 315 320
Pro Lys Tyr Val Lys Ser Thr Lys Leu Arg Met Ala Thr Gly Leu Arg
325 330 335
Asn Ile Pro Ser Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly
340 345 350
Phe Ile Glu Gly Gly Trp Thr Gly Met Ile Asp Gly Trp Tyr Gly Tyr
355 360 365
His His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser
370 375 380
Thr Gln Asn Ala Ile Asp Gly Ile Thr Asn Lys Val Asn Ser Val Ile
385 390 395 400
Glu Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Ser His
405 410 415
Leu Glu Arg Arg Ile Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe
420 425 430
Leu Asp Ile Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn
435 440 445
Glu Arg Thr Leu Asp Tyr His Asp Ser Asn Val Lys Asn Leu Tyr Glu
450 455 460
Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
465 470 475 480
Cys Phe Glu Phe Tyr His Lys Cys Asp Asp Thr Cys Met Glu Ser Val
485 490 495
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys Leu
500 505 510
Asn Arg Glu Glu Ile Asp Gly Val Lys Leu Glu Ser Thr Arg Val Tyr
515 520 525
Gln Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Val
530 535 540
Val Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu
545 550 555 560
Gln Cys Arg Ile Cys Ile
565
<210> 13
<211> 2148
<212> DNA
<213> 猪流感病毒
<400> 13
atggaagact ttgtgcgaca atgcttcaat ccaatgatcg tcgagcttgc ggaaaaggca 60
atgaaagaat atggagaaga tccgaaaatt gaaactaaca aattcgctgc aatatgcaca 120
cacttggaag tatgtttcat gtattcagat ttccatttca ttgacgagcg gggtgaatca 180
atcattgtag aatctggtga tccaaatgca ttactgaagc accgatttga gataattgaa 240
ggacgagacc ggaccatggc ctggacagta gtgaacagta tctgcaacac cacaggggta 300
gagaagccta aatttcttcc ggatttatac gactacaaag aaaatcggtt cattgaaatt 360
ggagtgacac gaagggaggt ccacatatac tacctagaga aagccaacaa aataaaatcc 420
gagaagacac acattcacat tttttcattc actggagagg agatggccac caaagcagac 480
tacacccttg atgaagaaag cagggcaaga atcaaaacca ggcttttcac cataagacaa 540
gaaatggcaa gtaggggtct atgggattcc tttcgtcagt ccgaaagagg cgaggagaca 600
attgaagaaa gatttgaaat tacaggaacc atgcgcagac ttgccgacca aagtctccca 660
ccgaacttct ccagtcttga aaactttaga gcttatgtag atgggttcga accaaacggc 720
tgcattgagg gcaagctttc tcaaatgtca aaagaagtga gcgcccaaat tgaacccttc 780
ttgaagacaa caccacgccc tctaaaattg cctgatgggc ctccttgctc tcagcggtca 840
aagttcttgc tgatggatgc tctgaaacta agtattgaag acccgagtca tgaaggagaa 900
ggaataccac tatatgatgc aatcaagtgc atgaagacat tttttggctg gaaagaaccc 960
aacataatca aaccacatga gaaaggcata aaccccaatt acctactggc ttggaagcag 1020
gtgctagcag agctccaaga cattgaaaat gaagagaaga tcccaaagac aaagaacatg 1080
aggagaacaa gccaattgaa gtgggcactc ggtgagaata tggcaccaga gaaagtagat 1140
tttgatgact gcaaagatgt tggtgatctt aaacagtatg acagcgacga gccagagccc 1200
agatctctag caagttgggt ccaaaatgaa ttcaacaagg catgtgaatt gaccgattca 1260
agctggatag aacttgatga gataggagaa gatattgcac cgattgaaca catcgcaagt 1320
atgaggagga actattttac agcagaagtg tcccattgta gggctacgga atacataatg 1380
aagggagtgt acataaacac ggctttgctt aatgcatctt gtgcagccat ggatgacttt 1440
cagctgatcc caatgataag caaatgcagg accaaagaag gaagacgaaa aacaaatctg 1500
tatgggttca ttataaaagg aaggtcccat ctgaggaatg atactgacgt ggtgaacttt 1560
gtaagcatgg agttctccct caccgacccg agactggagc cacacaaatg ggaaaaatac 1620
tgtgttcttg aaataggaga catgctcctg aggactgcga taggccaagt gtcgaggccc 1680
atgttcttat atgtgagaac caatggaacc tccaagatca agatgaaatg gggcatggaa 1740
atgaggcgct gccttcttca atctcttcag cagattgaga gcatgattga ggctgagtct 1800
tctgtaaaag agaaagacat gaccaaggaa ttttttgaaa acaaatcgga aacatggcca 1860
attggagaat cacccaaagg agtggaggaa ggctctattg ggaaagtgtg caggacctta 1920
ctggcaaaat ctgtattcaa cagtctatac gcgtctccac aacttgaggg attttcggct 1980
gaatcgagaa agttgcttct cattgttcag gcacttaggg acaacctgga acctggaacc 2040
ttcgatcttg gggggctata tgaagcaatc gaggagtgcc tgattaatga tccctgggtt 2100
ttgcttaatg catcttggtt caactccttc ctcacacatg cactgaaa 2148
<210> 14
<211> 716
<212> PRT
<213> 猪流感病毒
<400> 14
Met Glu Asp Phe Val Arg Gln Cys Phe Asn Pro Met Ile Val Glu Leu
1 5 10 15
Ala Glu Lys Ala Met Lys Glu Tyr Gly Glu Asp Pro Lys Ile Glu Thr
20 25 30
Asn Lys Phe Ala Ala Ile Cys Thr His Leu Glu Val Cys Phe Met Tyr
35 40 45
Ser Asp Phe His Phe Ile Asp Glu Arg Gly Glu Ser Ile Ile Val Glu
50 55 60
Ser Gly Asp Pro Asn Ala Leu Leu Lys His Arg Phe Glu Ile Ile Glu
65 70 75 80
Gly Arg Asp Arg Thr Met Ala Trp Thr Val Val Asn Ser Ile Cys Asn
85 90 95
Thr Thr Gly Val Glu Lys Pro Lys Phe Leu Pro Asp Leu Tyr Asp Tyr
100 105 110
Lys Glu Asn Arg Phe Ile Glu Ile Gly Val Thr Arg Arg Glu Val His
115 120 125
Ile Tyr Tyr Leu Glu Lys Ala Asn Lys Ile Lys Ser Glu Lys Thr His
130 135 140
Ile His Ile Phe Ser Phe Thr Gly Glu Glu Met Ala Thr Lys Ala Asp
145 150 155 160
Tyr Thr Leu Asp Glu Glu Ser Arg Ala Arg Ile Lys Thr Arg Leu Phe
165 170 175
Thr Ile Arg Gln Glu Met Ala Ser Arg Gly Leu Trp Asp Ser Phe Arg
180 185 190
Gln Ser Glu Arg Gly Glu Glu Thr Ile Glu Glu Arg Phe Glu Ile Thr
195 200 205
Gly Thr Met Arg Arg Leu Ala Asp Gln Ser Leu Pro Pro Asn Phe Ser
210 215 220
Ser Leu Glu Asn Phe Arg Ala Tyr Val Asp Gly Phe Glu Pro Asn Gly
225 230 235 240
Cys Ile Glu Gly Lys Leu Ser Gln Met Ser Lys Glu Val Ser Ala Gln
245 250 255
Ile Glu Pro Phe Leu Lys Thr Thr Pro Arg Pro Leu Lys Leu Pro Asp
260 265 270
Gly Pro Pro Cys Ser Gln Arg Ser Lys Phe Leu Leu Met Asp Ala Leu
275 280 285
Lys Leu Ser Ile Glu Asp Pro Ser His Glu Gly Glu Gly Ile Pro Leu
290 295 300
Tyr Asp Ala Ile Lys Cys Met Lys Thr Phe Phe Gly Trp Lys Glu Pro
305 310 315 320
Asn Ile Ile Lys Pro His Glu Lys Gly Ile Asn Pro Asn Tyr Leu Leu
325 330 335
Ala Trp Lys Gln Val Leu Ala Glu Leu Gln Asp Ile Glu Asn Glu Glu
340 345 350
Lys Ile Pro Lys Thr Lys Asn Met Arg Arg Thr Ser Gln Leu Lys Trp
355 360 365
Ala Leu Gly Glu Asn Met Ala Pro Glu Lys Val Asp Phe Asp Asp Cys
370 375 380
Lys Asp Val Gly Asp Leu Lys Gln Tyr Asp Ser Asp Glu Pro Glu Pro
385 390 395 400
Arg Ser Leu Ala Ser Trp Val Gln Asn Glu Phe Asn Lys Ala Cys Glu
405 410 415
Leu Thr Asp Ser Ser Trp Ile Glu Leu Asp Glu Ile Gly Glu Asp Ile
420 425 430
Ala Pro Ile Glu His Ile Ala Ser Met Arg Arg Asn Tyr Phe Thr Ala
435 440 445
Glu Val Ser His Cys Arg Ala Thr Glu Tyr Ile Met Lys Gly Val Tyr
450 455 460
Ile Asn Thr Ala Leu Leu Asn Ala Ser Cys Ala Ala Met Asp Asp Phe
465 470 475 480
Gln Leu Ile Pro Met Ile Ser Lys Cys Arg Thr Lys Glu Gly Arg Arg
485 490 495
Lys Thr Asn Leu Tyr Gly Phe Ile Ile Lys Gly Arg Ser His Leu Arg
500 505 510
Asn Asp Thr Asp Val Val Asn Phe Val Ser Met Glu Phe Ser Leu Thr
515 520 525
Asp Pro Arg Leu Glu Pro His Lys Trp Glu Lys Tyr Cys Val Leu Glu
530 535 540
Ile Gly Asp Met Leu Leu Arg Thr Ala Ile Gly Gln Val Ser Arg Pro
545 550 555 560
Met Phe Leu Tyr Val Arg Thr Asn Gly Thr Ser Lys Ile Lys Met Lys
565 570 575
Trp Gly Met Glu Met Arg Arg Cys Leu Leu Gln Ser Leu Gln Gln Ile
580 585 590
Glu Ser Met Ile Glu Ala Glu Ser Ser Val Lys Glu Lys Asp Met Thr
595 600 605
Lys Glu Phe Phe Glu Asn Lys Ser Glu Thr Trp Pro Ile Gly Glu Ser
610 615 620
Pro Lys Gly Val Glu Glu Gly Ser Ile Gly Lys Val Cys Arg Thr Leu
625 630 635 640
Leu Ala Lys Ser Val Phe Asn Ser Leu Tyr Ala Ser Pro Gln Leu Glu
645 650 655
Gly Phe Ser Ala Glu Ser Arg Lys Leu Leu Leu Ile Val Gln Ala Leu
660 665 670
Arg Asp Asn Leu Glu Pro Gly Thr Phe Asp Leu Gly Gly Leu Tyr Glu
675 680 685
Ala Ile Glu Glu Cys Leu Ile Asn Asp Pro Trp Val Leu Leu Asn Ala
690 695 700
Ser Trp Phe Asn Ser Phe Leu Thr His Ala Leu Lys
705 710 715
<210> 15
<211> 2271
<212> DNA
<213> 猪流感病毒
<400> 15
atggatgtca acccgactct acttttccta aaggttccag cgcaaaatgc cataagcacc 60
acattccctt atactggaga tcctccatac agccatggaa caggaacagg atacaccatg 120
gacacagtca acagaacaca ccagtattca gaaaaaggga aatggacgac aaacacagag 180
actggggcac cccagctcaa cccgattgat ggaccactac ccgatgataa tgaaccaagt 240
gggtatgcac aaacagactg tgtcctggag gccatggctt tccttgaaga atcccaccca 300
gggatatttg agaattcatg ccttgaaaca atggaaattg tccaacaaac aagggtggat 360
aaactaactc aaggtcgcca gacttatgat tggacattaa acagaaatca accggcagca 420
actgcattgg ccaacaccat agaagttttt agatcaaacg gtctaacagc taatgagtca 480
ggaaggctaa tagatttcct aaaggatgta atggaatcaa tggataagga ggaaatagag 540
ataacaacac attttcaaag aaaaaggaga gtaagagaca acatgaccaa gaagatggtc 600
acacaaagaa caatagggaa gaaaaaacaa aaattgaata agagaagtta tctaataaga 660
gcactgacat tgaatacgat gaccaaagat gcagagagag gcaagttaaa aaggagggct 720
atcgcaacac ctgggatgca gattagaggg ttcgtgtact ttgttgagac tttagctaga 780
agcatctgcg aaaagcttga acagtccgga ctcccagtag ggggcaatga aaagaaagcc 840
aaattggcaa atgttgtgag aaagatgatg actaattcac aagacacaga gctttctttc 900
acaatcactg gagataacac taaatggaat gaaaaccaga atcctcgaat gttcctggcg 960
atgatcacat acattaccag aaatcaaccc gagtggttca gaaacatact gagtatggca 1020
ccaataatgt tctcaaacaa aatggcaaga ctaggaaaag ggtacatgtt cgagagtaaa 1080
agaatgaagc tccgaacaca ggtaccagca gaaatgctag caagcattga tcttaagtat 1140
ttcaatgaat caacaaggaa gaaaattgag aaaataaggc ctctcctaat agatggcaca 1200
gcatcattga gccctgggat gatgatgggc atgttcaaca tgctaagtac ggttttggga 1260
gtctcaatac tgaatcttgg acaaaagaaa tacaccagga caacatactg gtgggatgga 1320
ctccaatcct cagacgattt tgccctcata gtaaatgcac caaatcatga gggaatacaa 1380
gcaggagtgg atagattcta caggacctgc aagttagtag ggatcaacat gagcaaaaag 1440
aagtcctata taaataagac tgggacattt gaattcacaa gcttttttta tcgctatggg 1500
tttgtagcta attttagcat ggagctgccc agttttggag tgtctggaat aaacgaatca 1560
gctgatatga gcatcggagt aacagtgata aagaacaaca tgataaataa tgatcttgga 1620
cctgcaacag cccagatggc cctccagttg ttcatcaaag actacagata cacatataga 1680
tgccatagag gggacacaca aatccagacg agaagatcat tcgagctaaa gagcctgtgg 1740
aatcaaactc aatcaaaggc aggattatta gtatctgatg gaggaccaaa tttatacaat 1800
atccggaatc ttcacattcc tgaagtctgc ttaaaatggg agctaatgga tgaggattat 1860
cggggaagac tttgtaatcc cctgaatccc tttgtcagcc ataaagagat tgattctgta 1920
aacagtgctg tggtgatgcc agcccatggt ccagccaaaa gtatggagta tgatgccgtt 1980
gcaactacac actcctggat tcccaagagg aaccgctcta ttctcaacac aagccaaagg 2040
ggaattcttg aggatgaaca gatgtaccag aagtgctgca acctgttcga gaaatttttc 2100
cctagtagtt catacagaag accagttgga atttctagca tggtggaggc catggtgtct 2160
agggcccgga ttgatgccag gattgacttc gagtctggac ggattaagaa agaagagttc 2220
tctgagatca tgaagatctg ttccaccatt gaagaactca gacggcaaaa g 2271
<210> 16
<211> 757
<212> PRT
<213> 猪流感病毒
<400> 16
Met Asp Val Asn Pro Thr Leu Leu Phe Leu Lys Val Pro Ala Gln Asn
1 5 10 15
Ala Ile Ser Thr Thr Phe Pro Tyr Thr Gly Asp Pro Pro Tyr Ser His
20 25 30
Gly Thr Gly Thr Gly Tyr Thr Met Asp Thr Val Asn Arg Thr His Gln
35 40 45
Tyr Ser Glu Lys Gly Lys Trp Thr Thr Asn Thr Glu Thr Gly Ala Pro
50 55 60
Gln Leu Asn Pro Ile Asp Gly Pro Leu Pro Asp Asp Asn Glu Pro Ser
65 70 75 80
Gly Tyr Ala Gln Thr Asp Cys Val Leu Glu Ala Met Ala Phe Leu Glu
85 90 95
Glu Ser His Pro Gly Ile Phe Glu Asn Ser Cys Leu Glu Thr Met Glu
100 105 110
Ile Val Gln Gln Thr Arg Val Asp Lys Leu Thr Gln Gly Arg Gln Thr
115 120 125
Tyr Asp Trp Thr Leu Asn Arg Asn Gln Pro Ala Ala Thr Ala Leu Ala
130 135 140
Asn Thr Ile Glu Val Phe Arg Ser Asn Gly Leu Thr Ala Asn Glu Ser
145 150 155 160
Gly Arg Leu Ile Asp Phe Leu Lys Asp Val Met Glu Ser Met Asp Lys
165 170 175
Glu Glu Ile Glu Ile Thr Thr His Phe Gln Arg Lys Arg Arg Val Arg
180 185 190
Asp Asn Met Thr Lys Lys Met Val Thr Gln Arg Thr Ile Gly Lys Lys
195 200 205
Lys Gln Lys Leu Asn Lys Arg Ser Tyr Leu Ile Arg Ala Leu Thr Leu
210 215 220
Asn Thr Met Thr Lys Asp Ala Glu Arg Gly Lys Leu Lys Arg Arg Ala
225 230 235 240
Ile Ala Thr Pro Gly Met Gln Ile Arg Gly Phe Val Tyr Phe Val Glu
245 250 255
Thr Leu Ala Arg Ser Ile Cys Glu Lys Leu Glu Gln Ser Gly Leu Pro
260 265 270
Val Gly Gly Asn Glu Lys Lys Ala Lys Leu Ala Asn Val Val Arg Lys
275 280 285
Met Met Thr Asn Ser Gln Asp Thr Glu Leu Ser Phe Thr Ile Thr Gly
290 295 300
Asp Asn Thr Lys Trp Asn Glu Asn Gln Asn Pro Arg Met Phe Leu Ala
305 310 315 320
Met Ile Thr Tyr Ile Thr Arg Asn Gln Pro Glu Trp Phe Arg Asn Ile
325 330 335
Leu Ser Met Ala Pro Ile Met Phe Ser Asn Lys Met Ala Arg Leu Gly
340 345 350
Lys Gly Tyr Met Phe Glu Ser Lys Arg Met Lys Leu Arg Thr Gln Val
355 360 365
Pro Ala Glu Met Leu Ala Ser Ile Asp Leu Lys Tyr Phe Asn Glu Ser
370 375 380
Thr Arg Lys Lys Ile Glu Lys Ile Arg Pro Leu Leu Ile Asp Gly Thr
385 390 395 400
Ala Ser Leu Ser Pro Gly Met Met Met Gly Met Phe Asn Met Leu Ser
405 410 415
Thr Val Leu Gly Val Ser Ile Leu Asn Leu Gly Gln Lys Lys Tyr Thr
420 425 430
Arg Thr Thr Tyr Trp Trp Asp Gly Leu Gln Ser Ser Asp Asp Phe Ala
435 440 445
Leu Ile Val Asn Ala Pro Asn His Glu Gly Ile Gln Ala Gly Val Asp
450 455 460
Arg Phe Tyr Arg Thr Cys Lys Leu Val Gly Ile Asn Met Ser Lys Lys
465 470 475 480
Lys Ser Tyr Ile Asn Lys Thr Gly Thr Phe Glu Phe Thr Ser Phe Phe
485 490 495
Tyr Arg Tyr Gly Phe Val Ala Asn Phe Ser Met Glu Leu Pro Ser Phe
500 505 510
Gly Val Ser Gly Ile Asn Glu Ser Ala Asp Met Ser Ile Gly Val Thr
515 520 525
Val Ile Lys Asn Asn Met Ile Asn Asn Asp Leu Gly Pro Ala Thr Ala
530 535 540
Gln Met Ala Leu Gln Leu Phe Ile Lys Asp Tyr Arg Tyr Thr Tyr Arg
545 550 555 560
Cys His Arg Gly Asp Thr Gln Ile Gln Thr Arg Arg Ser Phe Glu Leu
565 570 575
Lys Ser Leu Trp Asn Gln Thr Gln Ser Lys Ala Gly Leu Leu Val Ser
580 585 590
Asp Gly Gly Pro Asn Leu Tyr Asn Ile Arg Asn Leu His Ile Pro Glu
595 600 605
Val Cys Leu Lys Trp Glu Leu Met Asp Glu Asp Tyr Arg Gly Arg Leu
610 615 620
Cys Asn Pro Leu Asn Pro Phe Val Ser His Lys Glu Ile Asp Ser Val
625 630 635 640
Asn Ser Ala Val Val Met Pro Ala His Gly Pro Ala Lys Ser Met Glu
645 650 655
Tyr Asp Ala Val Ala Thr Thr His Ser Trp Ile Pro Lys Arg Asn Arg
660 665 670
Ser Ile Leu Asn Thr Ser Gln Arg Gly Ile Leu Glu Asp Glu Gln Met
675 680 685
Tyr Gln Lys Cys Cys Asn Leu Phe Glu Lys Phe Phe Pro Ser Ser Ser
690 695 700
Tyr Arg Arg Pro Val Gly Ile Ser Ser Met Val Glu Ala Met Val Ser
705 710 715 720
Arg Ala Arg Ile Asp Ala Arg Ile Asp Phe Glu Ser Gly Arg Ile Lys
725 730 735
Lys Glu Glu Phe Ser Glu Ile Met Lys Ile Cys Ser Thr Ile Glu Glu
740 745 750
Leu Arg Arg Gln Lys
755
<210> 17
<211> 2277
<212> DNA
<213> 猪流感病毒
<400> 17
atggagagaa taaaagaact aagagatctg atgtcgcagt ctcgcactcg cgagatactc 60
acaaagacca ctgtggacca tatggccata atcaaaaagt acacatcagg aaggcaagag 120
aagaaccccg cactcagaat gaagtggatg atggcaatga aatacccaat tacagcagac 180
aagagaataa tggacatgat tccagagagg aatgaacaag gacaaaccct ctggagcaaa 240
acaaacgatg ctggatcgga ccgtgtgatg gtatcacccc tggccgtaac atggtggaat 300
aggaatggcc caacaacaag cacagttcac taccctaagg tatataaaac ttatttcgaa 360
aagatcgaaa ggttaaaaca tggtatcttt ggccctgtcc acttcagaaa tcaagttaaa 420
ataagaagga gggttgacac aaaccctggt catgcagatc tcagtgccaa ggaggcacag 480
gatgtgatca tggaagttgt tttcccaaat gaagtggggg caagagtact gacgtcagag 540
tcacagctga caataacaaa ggaaaagaaa gaagagctcc aggattgtaa gattgctccc 600
ctgatggtgg catacatgct agaaagagag ttggttcgca agacgaggtt tctcccggtg 660
gctggtggaa caagcagtgt ttatattgaa gtgctacact taactcaggg aacatgctgg 720
gaacaaatgt acactccagg aggagaagtg agaaatgatg atgttgacca aagtttgatt 780
atcgctgcta gaaacatagt aagaagagca gcagtgtcag cagacccatt agcatctctc 840
ttggaaatgt gccacagcac acagattgga ggaataagga tggtggacat ccttagacag 900
aacccaacgg aggaacaagc cgtagacata tgcaaggcag caatggggct gaggattagc 960
tcttctttca gctttggtgg gttcaccttc aaaagaacaa gcggatcatc agttaagaaa 1020
gaagaagaag tgctcacggg caacctccaa acactgaaaa taagagtaca tgaaggatat 1080
gaagaattca caatggtagg gagaagagca actgctattc tcagaaaagc aaccaggaga 1140
ttgatccagt taatagtaag tgggagagac gatcaatcaa ttgctgaggc aataattgta 1200
gccatggtat tttcacaaga ggattgcatg atcaaggcag ttaggggcga tctgaacttt 1260
gtcaataggg caaaccagcg actgaatccc atgcaccaac tcttgaggca tttccaaaaa 1320
gatgcaaaag tgcttttcca gaactgggga attgaaccca tcgacagtgt gatgggaatg 1380
atcgggatat tgcctgatat gaccccaagc acggaaatgt cgctgagagg tataagagtc 1440
agcaaaatgg gagtagatga gtattccagc acggagagag tggtagtgag cattgaccga 1500
tttttgagag ttcgggatca acgagggaac gtactattgt cccccgaaga ggtcagcgag 1560
acacaaggaa ctgagaaatt gacaataact tattcgtcat caatgatgtg ggagatcaat 1620
ggtcctgagt cagtgctggt caacacttat caatggatca taaggaattg ggaaagcttg 1680
aaaattcaat ggtcacaaga tcccacgatg ttatacaaca aaatggaatt tgaaccattc 1740
cagtctcttg tccctaaggc aaccagaagt cgttacagtg gattcgtgag gacactgttc 1800
cagcaaatgc gggatgtgct tggaacattt gacactgtcc aaataataaa acttctcccc 1860
tttgctgctg ctccaccgga acagagtagg atacagttct cctcgctgac tgtgaatgtg 1920
agaggatcag ggctgaggat actggtaaga ggcaattctc cagtgttcaa ttacaacaaa 1980
gcaaccaaaa ggcttacaat tcttggaaaa gatgcaggtg cattgactga agatccagat 2040
gaaggcacag ctggagtgga gtctgctgtc ctgaggggat tcctcatttt gggtaaagaa 2100
gacaagagat atggcccagc attaagcatc aatgaactga gcaatcttgc aaaaggagag 2160
aaggctaatg tgttaattgg gcaaggagac gtggtgttgg taatgaaacg gaaacggaac 2220
tctagcatac ttactgacag ccagacagcg accaaaagaa ttcggatggc catcaat 2277
<210> 18
<211> 759
<212> PRT
<213> 猪流感病毒
<400> 18
Met Glu Arg Ile Lys Glu Leu Arg Asp Leu Met Ser Gln Ser Arg Thr
1 5 10 15
Arg Glu Ile Leu Thr Lys Thr Thr Val Asp His Met Ala Ile Ile Lys
20 25 30
Lys Tyr Thr Ser Gly Arg Gln Glu Lys Asn Pro Ala Leu Arg Met Lys
35 40 45
Trp Met Met Ala Met Lys Tyr Pro Ile Thr Ala Asp Lys Arg Ile Met
50 55 60
Asp Met Ile Pro Glu Arg Asn Glu Gln Gly Gln Thr Leu Trp Ser Lys
65 70 75 80
Thr Asn Asp Ala Gly Ser Asp Arg Val Met Val Ser Pro Leu Ala Val
85 90 95
Thr Trp Trp Asn Arg Asn Gly Pro Thr Thr Ser Thr Val His Tyr Pro
100 105 110
Lys Val Tyr Lys Thr Tyr Phe Glu Lys Ile Glu Arg Leu Lys His Gly
115 120 125
Ile Phe Gly Pro Val His Phe Arg Asn Gln Val Lys Ile Arg Arg Arg
130 135 140
Val Asp Thr Asn Pro Gly His Ala Asp Leu Ser Ala Lys Glu Ala Gln
145 150 155 160
Asp Val Ile Met Glu Val Val Phe Pro Asn Glu Val Gly Ala Arg Val
165 170 175
Leu Thr Ser Glu Ser Gln Leu Thr Ile Thr Lys Glu Lys Lys Glu Glu
180 185 190
Leu Gln Asp Cys Lys Ile Ala Pro Leu Met Val Ala Tyr Met Leu Glu
195 200 205
Arg Glu Leu Val Arg Lys Thr Arg Phe Leu Pro Val Ala Gly Gly Thr
210 215 220
Ser Ser Val Tyr Ile Glu Val Leu His Leu Thr Gln Gly Thr Cys Trp
225 230 235 240
Glu Gln Met Tyr Thr Pro Gly Gly Glu Val Arg Asn Asp Asp Val Asp
245 250 255
Gln Ser Leu Ile Ile Ala Ala Arg Asn Ile Val Arg Arg Ala Ala Val
260 265 270
Ser Ala Asp Pro Leu Ala Ser Leu Leu Glu Met Cys His Ser Thr Gln
275 280 285
Ile Gly Gly Ile Arg Met Val Asp Ile Leu Arg Gln Asn Pro Thr Glu
290 295 300
Glu Gln Ala Val Asp Ile Cys Lys Ala Ala Met Gly Leu Arg Ile Ser
305 310 315 320
Ser Ser Phe Ser Phe Gly Gly Phe Thr Phe Lys Arg Thr Ser Gly Ser
325 330 335
Ser Val Lys Lys Glu Glu Glu Val Leu Thr Gly Asn Leu Gln Thr Leu
340 345 350
Lys Ile Arg Val His Glu Gly Tyr Glu Glu Phe Thr Met Val Gly Arg
355 360 365
Arg Ala Thr Ala Ile Leu Arg Lys Ala Thr Arg Arg Leu Ile Gln Leu
370 375 380
Ile Val Ser Gly Arg Asp Asp Gln Ser Ile Ala Glu Ala Ile Ile Val
385 390 395 400
Ala Met Val Phe Ser Gln Glu Asp Cys Met Ile Lys Ala Val Arg Gly
405 410 415
Asp Leu Asn Phe Val Asn Arg Ala Asn Gln Arg Leu Asn Pro Met His
420 425 430
Gln Leu Leu Arg His Phe Gln Lys Asp Ala Lys Val Leu Phe Gln Asn
435 440 445
Trp Gly Ile Glu Pro Ile Asp Ser Val Met Gly Met Ile Gly Ile Leu
450 455 460
Pro Asp Met Thr Pro Ser Thr Glu Met Ser Leu Arg Gly Ile Arg Val
465 470 475 480
Ser Lys Met Gly Val Asp Glu Tyr Ser Ser Thr Glu Arg Val Val Val
485 490 495
Ser Ile Asp Arg Phe Leu Arg Val Arg Asp Gln Arg Gly Asn Val Leu
500 505 510
Leu Ser Pro Glu Glu Val Ser Glu Thr Gln Gly Thr Glu Lys Leu Thr
515 520 525
Ile Thr Tyr Ser Ser Ser Met Met Trp Glu Ile Asn Gly Pro Glu Ser
530 535 540
Val Leu Val Asn Thr Tyr Gln Trp Ile Ile Arg Asn Trp Glu Ser Leu
545 550 555 560
Lys Ile Gln Trp Ser Gln Asp Pro Thr Met Leu Tyr Asn Lys Met Glu
565 570 575
Phe Glu Pro Phe Gln Ser Leu Val Pro Lys Ala Thr Arg Ser Arg Tyr
580 585 590
Ser Gly Phe Val Arg Thr Leu Phe Gln Gln Met Arg Asp Val Leu Gly
595 600 605
Thr Phe Asp Thr Val Gln Ile Ile Lys Leu Leu Pro Phe Ala Ala Ala
610 615 620
Pro Pro Glu Gln Ser Arg Ile Gln Phe Ser Ser Leu Thr Val Asn Val
625 630 635 640
Arg Gly Ser Gly Leu Arg Ile Leu Val Arg Gly Asn Ser Pro Val Phe
645 650 655
Asn Tyr Asn Lys Ala Thr Lys Arg Leu Thr Ile Leu Gly Lys Asp Ala
660 665 670
Gly Ala Leu Thr Glu Asp Pro Asp Glu Gly Thr Ala Gly Val Glu Ser
675 680 685
Ala Val Leu Arg Gly Phe Leu Ile Leu Gly Lys Glu Asp Lys Arg Tyr
690 695 700
Gly Pro Ala Leu Ser Ile Asn Glu Leu Ser Asn Leu Ala Lys Gly Glu
705 710 715 720
Lys Ala Asn Val Leu Ile Gly Gln Gly Asp Val Val Leu Val Met Lys
725 730 735
Arg Lys Arg Asn Ser Ser Ile Leu Thr Asp Ser Gln Thr Ala Thr Lys
740 745 750
Arg Ile Arg Met Ala Ile Asn
755
<210> 19
<211> 979
<212> DNA
<213> 猪流感病毒
<400> 19
atgagtcttc taaccgaggt cgaaacgtat gttctctcta tcgtcccgtc aggccccctc 60
aaagccgaga tagcacagag gctcgaagac gtttttgcag ggaaaaacac cgatcttgag 120
gctctcatgg aatggctaaa gacaagacca atcctgtcac ctctgactaa agggatttta 180
gggtttgtgt tcacgctcac cgtgcccagt gagcgaggac tgcagcgtag acgttttgtc 240
cagaatgccc tcaatgggaa tggtgaccca aacaacatgg acaaggcggt aaaactgtac 300
aggaaactaa aaagggaaat aacattccat ggggccaagg aagtagcgct cagttactct 360
gctggtgcac ttgccagttg catgggcctc atatacaaca gaatggggac tgtcgccact 420
gaggtggcat ttggtctggt atgcgcaacc tgtgaacaaa ttgctgattc tcagcatcga 480
tctcatagac aaatggtgac aacaaccaat ccactaatca ggcacgagaa cagaatggta 540
atagccagca caacagctaa ggccatggaa caaatggctg gatcaagtga acaagcagca 600
gaggctatgg aggttgccag tcaggctaga caaatggtac aggcaatgag aacaattggg 660
actcacccta gttccagcac tggtctaaaa gatgatcttc ttgaaaattt acaggcctat 720
cagaaacgga tgggagtgca aatgcaacga ttcaagtgat cctctcattg atgccgcaag 780
catcattggt attttgcacc tgatattgtg gattcttgat cgtctttttt tcaaatgcat 840
ctaccgtcgc tttaaatacg gtctgcaaag agggccttct acggaaggag tgccggagtc 900
catgagggaa gaatatcggc agaaacagca gagtgctgtg gatgttgacg atggtcattt 960
tgtcaacata gtgctagag 979
<210> 20
<211> 835
<212> DNA
<213> 猪流感病毒
<400> 20
atggactcca atactgtgtc aagctttcag gtagactgtt tcctttggca catccgcaaa 60
cgatttgcag acaatggatt gggtgatgcc ccattccttg atcggctccg ccgagatcaa 120
aagtccctaa aaggaagggg caacaccctt agcctagaca tcgaaacagc cactcttgtt 180
gggaaacaaa ttgttgagtg gattttgaaa gaggaatcca gcgatatact taagatgacc 240
attgcatctg tgcctacttc gcgctaccta gctgacatga ccctcgagga aatgtcacga 300
gactggttca tgctaatgcc taggcaaaag ataataggcc ctctttgtgt gcgagtggac 360
caggcgatca tggaaaagaa catcatactg aaagcgaact tcagtgtgat ctttaaccga 420
ttagagactt tgatactact aagggctttc actgaggagg gagcaatcgt tggagaaatt 480
tcaccattac cttatcttcc aggacatact aatgaggatg tcaaaaatgc agttggggtc 540
ctcatcggag ggcttgaatg gaatggtaac acggttcgag gctctgaaaa tctacagaga 600
ttcgcttgga gaaaccataa tgaggatggg agatcttcac tacctccaga acagaaatga 660
aaagtggcga gagcaattgg gacagaaatt tgaggaaata agatggttaa ttgaagaaat 720
acggcacaga ttgaaagcga cagaaaatag tttcgagcaa ataacattta tgcaagcctt 780
acaactactg cttgaagtag aacaagagat aaggactttc tcgtttcagc ttatt 835
<210> 21
<211> 1698
<212> DNA
<213> 猪流感病毒
<400> 21
atgaaggcaa tactagtagt tctgctatat acatttgcaa cctcaaatgc agacacatta 60
tgtataggtt atcatgcgaa caattcaaca gacactgtag acacagtact agaaaagaat 120
gtaacagtaa cacactctgt taaccttcta gaagacaagc ataacgggaa actatgcaaa 180
ctaagagggg tagccccatt gcatttgggt aaatgtaaca ttgctggctg gatcctggga 240
aatccagagt gtgaatcact ctccacagca agctcatggt cctacattgt ggaaacatct 300
agttcaggca atggaacgtg ttacccagga gatttcatcg attatgagga gctaagagag 360
caattgagct cagtgtcatc atttgaaagg tttgagatat tccccaagac aagttcatgg 420
cccaatcatg aatcgaacaa aggtgtaacg gcagcatgtc ctcatgctgg agaaaaaagc 480
ttctacaaaa atttaatatg gctagttaaa aaaggaaact catacccaaa gctcagcaaa 540
tcctacatta atgataaagg gaaagaagtc ctcgtgctat ggggcattca ccatccatct 600
actagtgctg accaacaaag tctctatcag aatgcagatg catatgtttt tgtggggaca 660
tcaagataca gcaagaagtt caagccggaa atagcaataa gacccaaagt gagggatcaa 720
gaagggagaa tgaactatta ctggacacta gtagagccgg gagacaaaat aacattcgaa 780
gcaactggaa atctagtggt accgagatat gcattcgcaa tggaaagaaa tgctggatct 840
ggtattatca tttcagatac accagtccac gattgcaata caacttgtca gacacccaag 900
ggtgctataa acaccagcct tccttttcag aatatacatc cgatcacaat tggaaaatgt 960
ccaaaatatg taaaaagcac aaaattgaga ctggccacag gattgaggaa tgtcccgtct 1020
attcaatcta gaggcctatt tggggccatt gccggtttca ttgaaggggg gtggacaggg 1080
atggtagatg gatggtacgg ttatcaccat caaaatgagc aggggtcagg atatgcagcc 1140
gacctgaaga gcacacagaa tgccattgac gagattacta acaaagtaaa ttctgttatt 1200
gaaaagatga atacacagtt cacagcagta ggtaaagagt tcaaccacct ggaaaaaaga 1260
atagagaatt taaataaaaa agttgatgat ggtttcctgg acatttggac ttacaatgcc 1320
gaactgttgg ttctattgga aaatgaaaga actttggact accacgattc aaatgtgaag 1380
aacttatatg aaaaggtaag aagccagtta aaaaacaatg ccaaggaaat tggaaacggc 1440
tgctttgaat tttaccacaa atgcgataac acgtgcatgg aaagtgtcaa aaatgggact 1500
tatgactacc caaaatactc agaggaagca aaattaaaca gagaagaaat agatggggta 1560
aagctggaat caacaaggat ttaccagatt ttggcgatct attcaactgt cgccagttca 1620
ttggtactgg tagtctccct gggggcaatc agtttctgga tgtgctctaa tgggtctcta 1680
cagtgtagaa tatgtatt 1698
<210> 22
<211> 1698
<212> DNA
<213> 人工序列
<220>
<223> HA-DO (去优化的)
<400> 22
atgaaggcaa tactagtagt tctgctatat acatttgcaa cctcaaatgc agacacatta 60
tgtataggtt atcatgcgaa caattcaaca gatacggtcg atacggtctt agaaaaaaat 120
gtcacggtca cgcattcggt caatttatta gaagataaac ataatggaaa attatgtaaa 180
ttacgtggag tcgcgccgtt acatttagga aaatgtaata tagcgggatg gatattagga 240
aatccggaat gtgaatcgtt atcgacggcg tcgtcgtggt cgtatatagt cgaaacgtcg 300
tcgtcgggaa atggaacgtg ttatccggga gattttatag attatgaaga attacgtgaa 360
caattatcgt cggtctcgtc gtttgaacgt tttgaaatat ttccgaaaac gtcgtcgtgg 420
ccgaatcatg aatcgaataa aggagtcacg gcggcgtgtc cgcatgcggg agaaaaatcg 480
ttttataaaa atttaatatg gctagtcaaa aaaggaaatt cgtatccgaa attatcgaaa 540
tcgtatataa atgataaagg aaaagaagtc ttagtcttat ggggaataca tcatccgtcg 600
acgtcggcgg atcaacaatc gttatatcaa aatgcggatg cgtatgtctt tgtcggaacg 660
tcgcgttatt cgaaaaaatt taaaccggaa atagcgatac gtccgaaagt ccgtgatcaa 720
gaaggacgca tgaattatta ttggacgcta gtcgaaccgg gagataaaat aacgtttgaa 780
gcgacgggaa atttagtcgt cccgcgttat gcgtttgcga tggaacgtaa tgcgggatcg 840
ggaataataa tatcggatac gccggtccat gattgtaata cgacgtgtca aacgccgaaa 900
ggagcgataa atacgtcgtt accgtttcaa aatatacatc cgataacgat aggaaaatgt 960
ccgaaatatg tcaaatcgac gaaattacgt ttagcgacgg gattacgtaa tgtcccgtcg 1020
atacaatcgc gtggattatt tggagcgata gcgggattta tagaaggagg atggacggga 1080
atggtcgatg gatggtatgg atatcatcat caaaatgaac aaggatcggg atatgcggcg 1140
gatttaaaat cgacgcaaaa tgcgatagat gaaataacga ataaagtcaa ttcggtcata 1200
gaaaaaatga atacgcaatt tacggcggtc ggaaaagaat ttaatcattt agaaaaacgt 1260
atagaaaatt taaataaaaa agtcgatgat ggatttttag atatatggac gtataatgcg 1320
gaattattag tcttattaga aaatgaacgt acgttagatt atcatgattc gaatgtcaaa 1380
aatttatatg aaaaagtccg ttcgcaatta aaaaataatg cgaaagaaat aggaaatgga 1440
tgttttgaat tttatcataa atgtgataat acgtgtatgg aatcggtcaa aaatggaacg 1500
tatgattatc cgaaatattc ggaagaagcg aaattaaatc gtgaagaaat agatggagtc 1560
aaattagaat cgacgcgtat atatcaaata ttagcgatat attcgacggt cgcgtcgtca 1620
ttggtactgg tagtctccct gggggcaatc agtttctgga tgtgctctaa tgggtctcta 1680
cagtgtagaa tatgtatt 1698
<210> 23
<211> 566
<212> PRT
<213> 猪流感病毒
<400> 23
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Ala Thr Ser Asn
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Leu Glu Asp Lys His Asn Gly Lys Leu Cys Lys Leu Arg Gly Val
50 55 60
Ala Pro Leu His Leu Gly Lys Cys Asn Ile Ala Gly Trp Ile Leu Gly
65 70 75 80
Asn Pro Glu Cys Glu Ser Leu Ser Thr Ala Ser Ser Trp Ser Tyr Ile
85 90 95
Val Glu Thr Ser Ser Ser Gly Asn Gly Thr Cys Tyr Pro Gly Asp Phe
100 105 110
Ile Asp Tyr Glu Glu Leu Arg Glu Gln Leu Ser Ser Val Ser Ser Phe
115 120 125
Glu Arg Phe Glu Ile Phe Pro Lys Thr Ser Ser Trp Pro Asn His Glu
130 135 140
Ser Asn Lys Gly Val Thr Ala Ala Cys Pro His Ala Gly Glu Lys Ser
145 150 155 160
Phe Tyr Lys Asn Leu Ile Trp Leu Val Lys Lys Gly Asn Ser Tyr Pro
165 170 175
Lys Leu Ser Lys Ser Tyr Ile Asn Asp Lys Gly Lys Glu Val Leu Val
180 185 190
Leu Trp Gly Ile His His Pro Ser Thr Ser Ala Asp Gln Gln Ser Leu
195 200 205
Tyr Gln Asn Ala Asp Ala Tyr Val Phe Val Gly Thr Ser Arg Tyr Ser
210 215 220
Lys Lys Phe Lys Pro Glu Ile Ala Ile Arg Pro Lys Val Arg Asp Gln
225 230 235 240
Glu Gly Arg Met Asn Tyr Tyr Trp Thr Leu Val Glu Pro Gly Asp Lys
245 250 255
Ile Thr Phe Glu Ala Thr Gly Asn Leu Val Val Pro Arg Tyr Ala Phe
260 265 270
Ala Met Glu Arg Asn Ala Gly Ser Gly Ile Ile Ile Ser Asp Thr Pro
275 280 285
Val His Asp Cys Asn Thr Thr Cys Gln Thr Pro Lys Gly Ala Ile Asn
290 295 300
Thr Ser Leu Pro Phe Gln Asn Ile His Pro Ile Thr Ile Gly Lys Cys
305 310 315 320
Pro Lys Tyr Val Lys Ser Thr Lys Leu Arg Leu Ala Thr Gly Leu Arg
325 330 335
Asn Val Pro Ser Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly
340 345 350
Phe Ile Glu Gly Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr
355 360 365
His His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser
370 375 380
Thr Gln Asn Ala Ile Asp Glu Ile Thr Asn Lys Val Asn Ser Val Ile
385 390 395 400
Glu Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn His
405 410 415
Leu Glu Lys Arg Ile Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe
420 425 430
Leu Asp Ile Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn
435 440 445
Glu Arg Thr Leu Asp Tyr His Asp Ser Asn Val Lys Asn Leu Tyr Glu
450 455 460
Lys Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly
465 470 475 480
Cys Phe Glu Phe Tyr His Lys Cys Asp Asn Thr Cys Met Glu Ser Val
485 490 495
Lys Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys Leu
500 505 510
Asn Arg Glu Glu Ile Asp Gly Val Lys Leu Glu Ser Thr Arg Ile Tyr
515 520 525
Gln Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Val
530 535 540
Val Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu
545 550 555 560
Gln Cys Arg Ile Cys Ile
565
<210> 24
<211> 1407
<212> DNA
<213> 猪流感病毒
<400> 24
atgaatccaa accaaaagat aataaccatt ggttcggtct gtatgacaat tggaatggct 60
aacttaatat tacaaattgg aaacataatc tcaatatgga ttagccactc aattcaactt 120
gggaatcaaa atcagattga aacatgcaat caaagcgtca ttacttatga aaacaacact 180
tgggtaaatc agacatatgt taacatcagc aacaccaact ttgctgctgg acagtcagtg 240
gtttccgtga aattagcggg caattcctct ctctgccctg ttagtggatg ggctatatac 300
agtaaagaca acagtgtaag aatcggttcc aagggggatg tgtttgtcat aagggaacca 360
ttcatatcat gctccccctt ggaatgcaga accttcttct tgactcaagg ggccttgcta 420
aatgacaaac attccaatgg aaccattaaa gacaggagcc catatcgaac cctaatgagc 480
tgtcctattg gtgaagttcc ctctccatac aactcaagat ttgagtcagt cgcttggtca 540
gcaagtgctt gtcatgatgg catcaattgg ctaacaattg gaatttctgg cccagacaat 600
ggggcagtgg ctgtgttaaa gtacaacggc ataataacag acactatcaa gagttggaga 660
aacaatatat tgagaacaca agagtctgaa tgtgcatgtg taaatggttc ttgctttact 720
gtaatgaccg atggaccaag taatggacag gcctcataca agatcttcag aatagaaaag 780
ggaaagatag tcaaatcagt cgaaatgaat gcccctaatt atcactatga ggaatgctcc 840
tgttatcctg attctagtga aatcacatgt gtgtgcaggg ataactggca tggctcgaat 900
cgaccgtggg tgtctttcaa ccagaatctg gaatatcaga taggatacat atgcagtggg 960
attttcggag acaatccacg ccctaatgat aagacaggca gttgtggtcc agtatcgtct 1020
aatggagcaa atggagtaaa agggttttca ttcaaatacg gcaatggtgt ttggataggg 1080
agaactaaaa gcattagttc aagaaacggt tttgagatga tttgggatcc gaacggatgg 1140
actgggacag acaataactt ctcaataaag caagatatcg taggaataaa tgagtggtca 1200
ggatatagcg ggagttttgt tcagcatcca gaactaacag ggctggattg tataagacct 1260
tgcttctggg ttgaactaat cagagggcga cccaaagaga acacaatctg gactagcggg 1320
agcagcatat ccttttgtgg tgtaaacagt gacactgtgg gttggtcttg gccagacggt 1380
gctgagttgc catttaccat tgacaag 1407
<210> 25
<211> 1407
<212> DNA
<213> 人工序列
<220>
<223> NA-DO (去优化的)
<400> 25
atgaatccaa accaaaagat aataaccatt ggttcggtct gtatgacaat tggaatggct 60
aacttaatat tacaaattgg aaacataatc tcaatatgga tttcgcattc gatacaatta 120
ggaaatcaaa atcaaataga aacgtgtaat caatcggtca taacgtatga aaataatacg 180
tgggtcaatc aaacgtatgt caatatatcg aatacgaatt ttgcggcggg acaatcggtc 240
gtatcggtca aattagcggg aaattcgtcg ttatgtccgg tctcgggatg ggcgatatat 300
tcgaaagata attcggtccg tataggatcg aaaggagatg tctttgtcat acgtgaaccg 360
tttatatcgt gttcgccgtt agaatgtcgt acgttttttt taacgcaagg agcgttatta 420
aatgataaac attcgaatgg aacgataaaa gatcgttcgc cgtatcgtac gttaatgtcg 480
tgtccgatag gagaagtccc gtcgccgtat aattcgcgtt ttgaatcggt cgcgtggtcg 540
gcgtcggcgt gtcatgatgg aataaattgg ttaacgatag gaatatcggg accggataat 600
ggagcggtcg cggtcttaaa atataatgga ataataacgg atacgataaa atcgtggcgt 660
aataatatat tacgtacgca agaatcggaa tgtgcgtgtg tcaatggatc gtgttttacg 720
gtcatgacgg atggaccgtc gaatggacaa gcgtcgtata aaatatttcg tatagaaaaa 780
ggaaaaatag tcaaatcggt cgaaatgaat gcgccgaatt atcattatga agaatgttcg 840
tgttatccgg attcgtcgga aataacgtgt gtctgtcgtg ataattggca tggatcgaat 900
cgtccgtggg tctcgtttaa tcaaaattta gaatatcaaa taggatatat atgttcggga 960
atatttggag ataatccgcg tccgaatgat aaaacgggat cgtgtggacc ggtctcgtcg 1020
aatggagcga atggagtcaa aggattttcg tttaaatatg gaaatggagt ctggatagga 1080
cgtacgaaat cgatatcgtc gcgtaatgga tttgaaatga tatgggatcc gaatggatgg 1140
acgggaacgg ataataattt ttcgataaaa caagatatag tcggaataaa tgaatggtcg 1200
ggatattcgg gatcgtttgt ccaacatccg gaattaacgg gattagattg tatacgtccg 1260
tgtttttggg tcgaattaat acgtggacgt ccgaaagaaa atacgatatg gactagcggg 1320
agcagcatat ccttttgtgg tgtaaacagt gacactgtgg gttggtcttg gccagacggt 1380
gctgagttgc catttaccat tgacaag 1407
<210> 26
<211> 469
<212> PRT
<213> 猪流感病毒
<400> 26
Met Asn Pro Asn Gln Lys Ile Ile Thr Ile Gly Ser Val Cys Met Thr
1 5 10 15
Ile Gly Met Ala Asn Leu Ile Leu Gln Ile Gly Asn Ile Ile Ser Ile
20 25 30
Trp Ile Ser His Ser Ile Gln Leu Gly Asn Gln Asn Gln Ile Glu Thr
35 40 45
Cys Asn Gln Ser Val Ile Thr Tyr Glu Asn Asn Thr Trp Val Asn Gln
50 55 60
Thr Tyr Val Asn Ile Ser Asn Thr Asn Phe Ala Ala Gly Gln Ser Val
65 70 75 80
Val Ser Val Lys Leu Ala Gly Asn Ser Ser Leu Cys Pro Val Ser Gly
85 90 95
Trp Ala Ile Tyr Ser Lys Asp Asn Ser Val Arg Ile Gly Ser Lys Gly
100 105 110
Asp Val Phe Val Ile Arg Glu Pro Phe Ile Ser Cys Ser Pro Leu Glu
115 120 125
Cys Arg Thr Phe Phe Leu Thr Gln Gly Ala Leu Leu Asn Asp Lys His
130 135 140
Ser Asn Gly Thr Ile Lys Asp Arg Ser Pro Tyr Arg Thr Leu Met Ser
145 150 155 160
Cys Pro Ile Gly Glu Val Pro Ser Pro Tyr Asn Ser Arg Phe Glu Ser
165 170 175
Val Ala Trp Ser Ala Ser Ala Cys His Asp Gly Ile Asn Trp Leu Thr
180 185 190
Ile Gly Ile Ser Gly Pro Asp Asn Gly Ala Val Ala Val Leu Lys Tyr
195 200 205
Asn Gly Ile Ile Thr Asp Thr Ile Lys Ser Trp Arg Asn Asn Ile Leu
210 215 220
Arg Thr Gln Glu Ser Glu Cys Ala Cys Val Asn Gly Ser Cys Phe Thr
225 230 235 240
Val Met Thr Asp Gly Pro Ser Asn Gly Gln Ala Ser Tyr Lys Ile Phe
245 250 255
Arg Ile Glu Lys Gly Lys Ile Val Lys Ser Val Glu Met Asn Ala Pro
260 265 270
Asn Tyr His Tyr Glu Glu Cys Ser Cys Tyr Pro Asp Ser Ser Glu Ile
275 280 285
Thr Cys Val Cys Arg Asp Asn Trp His Gly Ser Asn Arg Pro Trp Val
290 295 300
Ser Phe Asn Gln Asn Leu Glu Tyr Gln Ile Gly Tyr Ile Cys Ser Gly
305 310 315 320
Ile Phe Gly Asp Asn Pro Arg Pro Asn Asp Lys Thr Gly Ser Cys Gly
325 330 335
Pro Val Ser Ser Asn Gly Ala Asn Gly Val Lys Gly Phe Ser Phe Lys
340 345 350
Tyr Gly Asn Gly Val Trp Ile Gly Arg Thr Lys Ser Ile Ser Ser Arg
355 360 365
Asn Gly Phe Glu Met Ile Trp Asp Pro Asn Gly Trp Thr Gly Thr Asp
370 375 380
Asn Asn Phe Ser Ile Lys Gln Asp Ile Val Gly Ile Asn Glu Trp Ser
385 390 395 400
Gly Tyr Ser Gly Ser Phe Val Gln His Pro Glu Leu Thr Gly Leu Asp
405 410 415
Cys Ile Arg Pro Cys Phe Trp Val Glu Leu Ile Arg Gly Arg Pro Lys
420 425 430
Glu Asn Thr Ile Trp Thr Ser Gly Ser Ser Ile Ser Phe Cys Gly Val
435 440 445
Asn Ser Asp Thr Val Gly Trp Ser Trp Pro Asp Gly Ala Glu Leu Pro
450 455 460
Phe Thr Ile Asp Lys
465
<210> 27
<211> 657
<212> DNA
<213> 人工序列
<220>
<223> A/猪/NC/3793/2008(H1N1)的NS1 DO CDS - TRIG, 去优化的
<400> 27
atggactcca atactgtgtc aagctttcag gtagactgtt tcctttggca catccgcaaa 60
cgatttgcag acaatggatt gggtgatgcc ccattccttg atcggctccg ccgagatcaa 120
aaatcgttaa aaggacgtgg aaatacgtta tcgttagata tagaaacggc gacgctagtc 180
ggaaaacaaa tagtcgaatg gatattaaaa gaagaatcgt cggatatatt aaaaatgacg 240
atagcgtcgg tcccgacgtc gcgttattta gcggatatga cgttagaaga aatgtcgcgt 300
gattggttta tgttaatgcc gcgtcaaaaa ataataggac cgttatgtgt ccgtgtcgat 360
caagcgataa tggaaaaaaa tataatatta aaagcgaatt tttcggtcat atttaatcgt 420
ttagaaacgt taatattatt acgtgcgttt acggaggagg gagcaatcgt tggagaaatt 480
tcaccattac cttatcttcc aggacatact aatgaggatg tcaaaaatgc agttggggtc 540
ctcatcggag ggcttgaatg gaatggtaac acggttcgag gctctgaaaa tctacagaga 600
ttcgcttgga gaaaccataa tgaggatggg agatcttcac tacctccaga acagaaa 657
<210> 28
<211> 1695
<212> DNA
<213> 猪流感病毒
<400> 28
atgaaagtaa aactaatggt tctgttatgt acatttacag ctacatatgc agacacaata 60
tgtgtaggct accatgccaa caactcaact gacactgttg acacagtact tgagaagaat 120
gtgacagtga cacactctgt caacctactt gaggacagcc acaatggaaa actatgtcta 180
ctaaaaggaa tagctccact acaattgggt agttgcagcg ttgccggatg gatcttagga 240
aacccagagt gcgaattgct gatttccaag gaatcttggt cctacattgt agaaacacca 300
aatcctgaga atggaacatg ttacccaggg tatttcacag actatgaaga actgagggag 360
caattgagtt cagtatcttc atttaagagg ttcgaaatat tccccaaaga gagctcatgg 420
cccaaccaca ccgtaaccgg agtgtcatca tcatgctccc ataacgggaa aagcagcttc 480
tacagaaatt tgctatggct gacggtgaag aacggtctgt acccaaacct gagcaagtcc 540
tatacaaaca aaaaggagaa agaagtcctt gtactatggg gtgttcatca cccatctaac 600
ataggggacc aaagggccct ctatcataca gaaaatgctt atgtctctgt agtgtcttca 660
cattatagca gaagattcac cccagaaata gccaaaagac ccaaggtgag aaatcaggaa 720
ggaagaatca actactactg gaccctgcta gaacccgggg atacaataat atttgaggca 780
aatggaaatc taatagcacc aaggtatgcc ttcgaactga gtaagggttt tggatcagga 840
atcatcacat caaatgcacc aatgggtgaa tgtaatgcaa agtgtcaaac acctcaggga 900
gctataaaca gcagtcttcc tttccagaat gtacacccag taacaatagg agagtgccca 960
aagtatgtca aaagtgcaaa attaaggatg gttacaggac taaggaacac cccatccatt 1020
caatccagag gtttgtttgg agccattgcc ggtttcattg aaggagggtg gactggaatg 1080
gtagatggtt ggtatggtta tcaccatcag aatgagcaag gatctgggta tgctgcagac 1140
caacaaagca cacaaaatgc cattaatggg attacaaaca aggtgaattc tgtgattgaa 1200
aaaatgaaca ctcaattcac agctgtgggc aaagaattca acaaactgga aagaagaatg 1260
gaaaacttaa ataaaaaggt tgatgatggg tttctagaca tttggacata taatgcagaa 1320
ttgttagttc tactggaaaa tgaaaggact ttggatttcc atgactccaa cgtgaagaat 1380
ctgtatgaga aagtaaaaag ccaattaaaa aataatgcca aagaaatagg aaacgggtgt 1440
tttgaattct atcataagtg taacgatgaa tgcatggaga gtgtgaaaaa tggaacttat 1500
gactatccaa aatattccga agaatcaaag ttaaacaggg agaaaattga tggagtgaaa 1560
ttggaatcaa tgggagtcta taatatcctg gcgatctact caacagtcgc cagttcccta 1620
gttcttttag tctccctggg ggcaatcagc ttctggatgt gttccaatgg gtctttacag 1680
tgtagaatat gcatc 1695
<210> 29
<211> 1695
<212> DNA
<213> 人工序列
<220>
<223> HA-DO (H1N2; 去优化的)
<400> 29
atgaaagtaa aactaatggt tctgttatgt acatttacag ctacatatgc agacacaata 60
tgtgtaggct accatgccaa caactcaact gatacggtcg atacggtctt agaaaaaaat 120
gtcacggtca cgcattcggt caatttatta gaagattcgc ataatggaaa attatgttta 180
ttaaaaggaa tagcgccgtt acaattagga tcgtgttcgg tcgcgggatg gatattagga 240
aatccggaat gtgaattatt aatatcgaaa gaatcgtggt cgtatatagt cgaaacgccg 300
aatccggaaa atggaacgtg ttatccggga tattttacgg attatgaaga attacgtgaa 360
caattatcgt cggtctcgtc gtttaaacgt tttgaaatat ttccgaaaga atcgtcgtgg 420
ccgaatcata cggtcacggg agtctcgtcg tcgtgttcgc ataatggaaa atcgtcgttt 480
tatcgtaatt tattatggtt aacggtcaaa aatggattat atccgaattt atcgaaatcg 540
tatacgaata aaaaagaaaa agaagtctta gtcttatggg gagtccatca tccgtcgaat 600
ataggagatc aacgtgcgtt atatcatacg gaaaatgcgt atgtctcggt cgtatcgtcg 660
cattattcgc gtcgttttac gccggaaata gcgaaacgtc cgaaagtccg taatcaagaa 720
ggacgtataa attattattg gacgttatta gaaccgggag atacgataat atttgaagcg 780
aatggaaatt taatagcgcc gcgttatgcg tttgaattat cgaaaggatt tggatcggga 840
ataataacgt cgaatgcgcc gatgggagaa tgtaatgcga aatgtcaaac gccgcaagga 900
gcgataaatt cgtcgttacc gtttcaaaat gtccatccgg tcacgatagg agaatgtccg 960
aaatatgtca aatcggcgaa attacgtatg gtcacgggat tacgtaatac gccgtcgata 1020
caatcgcgtg gattatttgg agcgatagcg ggatttatag aaggaggatg gacgggaatg 1080
gtcgatggat ggtatggata tcatcatcaa aatgaacaag gatcgggata tgcggcggat 1140
caacaatcga cgcaaaatgc gataaatgga ataacgaata aagtcaattc ggtcatagaa 1200
aaaatgaata cgcaatttac ggcggtcgga aaagaattta ataaattaga acgtcgtatg 1260
gaaaatttaa ataaaaaagt cgatgatgga tttttagata tatggacgta taatgcggaa 1320
ttattagtct tattagaaaa tgaacgtacg ttagattttc atgattcgaa tgtcaaaaat 1380
ttatatgaaa aagtcaaatc gcaattaaaa aataatgcga aagaaatagg aaatggatgt 1440
tttgaatttt atcataaatg taatgatgaa tgtatggaat cggtcaaaaa tggaacgtat 1500
gattatccga aatattcgga agaatcgaaa ttaaatcgtg aaaaaataga tggagtcaaa 1560
ttagaatcga tgggagtcta taatatatta gcgatatatt cgacggtcgc gtcgtcccta 1620
gttcttttag tctccctggg ggcaatcagc ttctggatgt gttccaatgg gtctttacag 1680
tgtagaatat gcatc 1695
<210> 30
<211> 565
<212> PRT
<213> 猪流感病毒
<400> 30
Met Lys Val Lys Leu Met Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Asp Thr Ile Cys Val Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Leu Glu Asp Ser His Asn Gly Lys Leu Cys Leu Leu Lys Gly Ile
50 55 60
Ala Pro Leu Gln Leu Gly Ser Cys Ser Val Ala Gly Trp Ile Leu Gly
65 70 75 80
Asn Pro Glu Cys Glu Leu Leu Ile Ser Lys Glu Ser Trp Ser Tyr Ile
85 90 95
Val Glu Thr Pro Asn Pro Glu Asn Gly Thr Cys Tyr Pro Gly Tyr Phe
100 105 110
Thr Asp Tyr Glu Glu Leu Arg Glu Gln Leu Ser Ser Val Ser Ser Phe
115 120 125
Lys Arg Phe Glu Ile Phe Pro Lys Glu Ser Ser Trp Pro Asn His Thr
130 135 140
Val Thr Gly Val Ser Ser Ser Cys Ser His Asn Gly Lys Ser Ser Phe
145 150 155 160
Tyr Arg Asn Leu Leu Trp Leu Thr Val Lys Asn Gly Leu Tyr Pro Asn
165 170 175
Leu Ser Lys Ser Tyr Thr Asn Lys Lys Glu Lys Glu Val Leu Val Leu
180 185 190
Trp Gly Val His His Pro Ser Asn Ile Gly Asp Gln Arg Ala Leu Tyr
195 200 205
His Thr Glu Asn Ala Tyr Val Ser Val Val Ser Ser His Tyr Ser Arg
210 215 220
Arg Phe Thr Pro Glu Ile Ala Lys Arg Pro Lys Val Arg Asn Gln Glu
225 230 235 240
Gly Arg Ile Asn Tyr Tyr Trp Thr Leu Leu Glu Pro Gly Asp Thr Ile
245 250 255
Ile Phe Glu Ala Asn Gly Asn Leu Ile Ala Pro Arg Tyr Ala Phe Glu
260 265 270
Leu Ser Lys Gly Phe Gly Ser Gly Ile Ile Thr Ser Asn Ala Pro Met
275 280 285
Gly Glu Cys Asn Ala Lys Cys Gln Thr Pro Gln Gly Ala Ile Asn Ser
290 295 300
Ser Leu Pro Phe Gln Asn Val His Pro Val Thr Ile Gly Glu Cys Pro
305 310 315 320
Lys Tyr Val Lys Ser Ala Lys Leu Arg Met Val Thr Gly Leu Arg Asn
325 330 335
Thr Pro Ser Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
340 345 350
Ile Glu Gly Gly Trp Thr Gly Met Val Asp Gly Trp Tyr Gly Tyr His
355 360 365
His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Gln Gln Ser Thr
370 375 380
Gln Asn Ala Ile Asn Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu
385 390 395 400
Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn Lys Leu
405 410 415
Glu Arg Arg Met Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu
420 425 430
Asp Ile Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn Glu
435 440 445
Arg Thr Leu Asp Phe His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys
450 455 460
Val Lys Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys
465 470 475 480
Phe Glu Phe Tyr His Lys Cys Asn Asp Glu Cys Met Glu Ser Val Lys
485 490 495
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ser Lys Leu Asn
500 505 510
Arg Glu Lys Ile Asp Gly Val Lys Leu Glu Ser Met Gly Val Tyr Asn
515 520 525
Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Leu Val
530 535 540
Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln
545 550 555 560
Cys Arg Ile Cys Ile
565
<210> 31
<211> 1407
<212> DNA
<213> 猪流感病毒
<400> 31
atgaatccaa atcaaaagat aataacgatt ggctctgttt ctcttactat tgccacaatg 60
tgcttcctta tgcaaattgc catcctggta actaatgtaa cattgcactt caatcaatat 120
gaatgcaact accccccaaa caaccaagta atactgtgtg aaccaacaat aatagaaaga 180
aacataacag agatagtgta tctgaccaac accaccatag agaaggaaat atgccccaaa 240
ctagcagaat acagaaattg gtcaaagccg caatgtaaaa ttacagggtt tgcacctttt 300
tccaaggaca attcgattag gctttctgct ggtggggaca tttgggtgac gagagaacct 360
tatgtgtcat gcgatcctga taagtgttat cagtttgccc ttggacaagg aacaacatta 420
aacaacaggc attcaaatga cacagtacat gataggaccc cttatcgaac cctattgatg 480
aatgagttgg gtattccatt ccatttgggg accaaacaag tgtgcatagc atggtccagc 540
tcaagttgtc atgatggaaa agcatggctt cacgtttgta ttactgggca tgatgaaaat 600
gcaactgcca gcatcattta caatggaaga cttgtagata gtattggttc atggtccaaa 660
aaaatactca ggacacagga gtcggaatgt gtttgcatca atggaacttg tacagtagta 720
atgactgatg ggagtgcttc aggaatagct gacactaaaa tattattcat tgaagagggg 780
aaaatcgttc atattagccc attgttagga agtgctcagc atgtagagga gtgctcctgt 840
tatccccgat atcctggtgt cagatgcatc tgtagagaca actggaaagg ttccaataga 900
cccgtcgtag atataaatgt aaaggattat agcattgttt ccagttatgt gtgctcagga 960
cttgttggag atacacccag aaaagacgac agatccagca gtagcgattg tctgaatcct 1020
aacaatgagg aaggggggca tggagtgaaa ggctgggcct ttgatgatgg aaatgatgtg 1080
tggatgggaa gaacaatcaa cgagacgtta cgctcaggtt atgaaacctt caaagtcatt 1140
gaaggctggt ccaaacctaa ttccaaattg cagataaata ggcaagtcat agttgaaaga 1200
ggtgataggt ccggttattc tggcattttc tctgttgaag gcaaaagctg tatcaatcgg 1260
tgcttttatg tggagttgat aagaggaagg aaacaggaaa ctgcagtatg gtggacgtca 1320
aacagtattg ttgtgttttg tggcacctca ggtacatatg gaacaggctc atggcctgat 1380
ggggcgaaca tcaatctcat gcctgta 1407
<210> 32
<211> 1407
<212> DNA
<213> 人工序列
<220>
<223> NA-DO (H1N2; 去优化的)
<400> 32
atgaatccaa atcaaaagat aataacgatt ggctctgttt ctcttactat tgccacaatg 60
tgcttcctta tgcaaattgc catcctggta actaatgtaa cattgcactt caatcaatat 120
gaatgtaatt atccgccgaa taatcaagtc atattatgtg aaccgacgat aatagaacgt 180
aatataacgg aaatagtcta tttaacgaat acgacgatag aaaaagaaat atgtccgaaa 240
ttagcggaat atcgtaattg gtcgaaaccg caatgtaaaa taacgggatt tgcgccgttt 300
tcgaaagata attcgatacg tttatcggcg ggaggagata tatgggtcac gcgtgaaccg 360
tatgtctcgt gtgatccgga taaatgttat caatttgcgt taggacaagg aacgacgtta 420
aataatcgtc attcgaatga tacggtccat gatcgtacgc cgtatcgcac gttattaatg 480
aatgaattag gaataccgtt tcatttagga acgaaacaag tctgtatagc gtggtcgtcg 540
tcgtcgtgtc atgatggaaa agcgtggtta catgtctgta taacgggaca tgatgaaaat 600
gcgacggcgt cgataatata taatggacgt ttagtcgatt cgataggatc gtggtcgaaa 660
aaaatattac gtacgcaaga atcggaatgt gtctgtataa atggaacgtg tacggtcgtc 720
atgacggatg gatcggcgtc gggaatagcg gatacgaaaa tattatttat agaagaagga 780
aaaatagtcc atatatcgcc gttattagga tcggcgcaac atgtcgaaga atgttcgtgt 840
tatccgcgtt atccgggagt ccgttgtata tgtcgtgata attggaaagg atcgaatcgt 900
ccggtcgtcg atataaatgt caaagattat tcgatagtct cgtcgtatgt ctgttcggga 960
ttagtcggag atacgccgcg taaagatgat cgttcgtcgt cgtcggattg tttaaatccg 1020
aataatgaag aaggaggaca tggagtcaaa ggatgggcgt ttgatgatgg aaatgatgtc 1080
tggatgggac gtacgataaa tgaaacgtta cgttcgggat atgaaacgtt taaagtcata 1140
gaaggatggt cgaaaccgaa ttcgaaatta caaataaatc gtcaagtcat agtcgaacgt 1200
ggagatcgtt cgggatattc gggaatattt tcggtcgaag gaaaatcgtg tataaatcgt 1260
tgtttttatg tcgaattaat acgtggacgt aaacaagaaa ctgcagtatg gtggacgtca 1320
aacagtattg ttgtgttttg tggcacctca ggtacatatg gaacaggctc atggcctgat 1380
ggggcgaaca tcaatctcat gcctgta 1407
<210> 33
<211> 469
<212> PRT
<213> 猪流感病毒
<400> 33
Met Asn Pro Asn Gln Lys Ile Ile Thr Ile Gly Ser Val Ser Leu Thr
1 5 10 15
Ile Ala Thr Met Cys Phe Leu Met Gln Ile Ala Ile Leu Val Thr Asn
20 25 30
Val Thr Leu His Phe Asn Gln Tyr Glu Cys Asn Tyr Pro Pro Asn Asn
35 40 45
Gln Val Ile Leu Cys Glu Pro Thr Ile Ile Glu Arg Asn Ile Thr Glu
50 55 60
Ile Val Tyr Leu Thr Asn Thr Thr Ile Glu Lys Glu Ile Cys Pro Lys
65 70 75 80
Leu Ala Glu Tyr Arg Asn Trp Ser Lys Pro Gln Cys Lys Ile Thr Gly
85 90 95
Phe Ala Pro Phe Ser Lys Asp Asn Ser Ile Arg Leu Ser Ala Gly Gly
100 105 110
Asp Ile Trp Val Thr Arg Glu Pro Tyr Val Ser Cys Asp Pro Asp Lys
115 120 125
Cys Tyr Gln Phe Ala Leu Gly Gln Gly Thr Thr Leu Asn Asn Arg His
130 135 140
Ser Asn Asp Thr Val His Asp Arg Thr Pro Tyr Arg Thr Leu Leu Met
145 150 155 160
Asn Glu Leu Gly Ile Pro Phe His Leu Gly Thr Lys Gln Val Cys Ile
165 170 175
Ala Trp Ser Ser Ser Ser Cys His Asp Gly Lys Ala Trp Leu His Val
180 185 190
Cys Ile Thr Gly His Asp Glu Asn Ala Thr Ala Ser Ile Ile Tyr Asn
195 200 205
Gly Arg Leu Val Asp Ser Ile Gly Ser Trp Ser Lys Lys Ile Leu Arg
210 215 220
Thr Gln Glu Ser Glu Cys Val Cys Ile Asn Gly Thr Cys Thr Val Val
225 230 235 240
Met Thr Asp Gly Ser Ala Ser Gly Ile Ala Asp Thr Lys Ile Leu Phe
245 250 255
Ile Glu Glu Gly Lys Ile Val His Ile Ser Pro Leu Leu Gly Ser Ala
260 265 270
Gln His Val Glu Glu Cys Ser Cys Tyr Pro Arg Tyr Pro Gly Val Arg
275 280 285
Cys Ile Cys Arg Asp Asn Trp Lys Gly Ser Asn Arg Pro Val Val Asp
290 295 300
Ile Asn Val Lys Asp Tyr Ser Ile Val Ser Ser Tyr Val Cys Ser Gly
305 310 315 320
Leu Val Gly Asp Thr Pro Arg Lys Asp Asp Arg Ser Ser Ser Ser Asp
325 330 335
Cys Leu Asn Pro Asn Asn Glu Glu Gly Gly His Gly Val Lys Gly Trp
340 345 350
Ala Phe Asp Asp Gly Asn Asp Val Trp Met Gly Arg Thr Ile Asn Glu
355 360 365
Thr Leu Arg Ser Gly Tyr Glu Thr Phe Lys Val Ile Glu Gly Trp Ser
370 375 380
Lys Pro Asn Ser Lys Leu Gln Ile Asn Arg Gln Val Ile Val Glu Arg
385 390 395 400
Gly Asp Arg Ser Gly Tyr Ser Gly Ile Phe Ser Val Glu Gly Lys Ser
405 410 415
Cys Ile Asn Arg Cys Phe Tyr Val Glu Leu Ile Arg Gly Arg Lys Gln
420 425 430
Glu Thr Ala Val Trp Trp Thr Ser Asn Ser Ile Val Val Phe Cys Gly
435 440 445
Thr Ser Gly Thr Tyr Gly Thr Gly Ser Trp Pro Asp Gly Ala Asn Ile
450 455 460
Asn Leu Met Pro Val
465
<210> 34
<211> 1698
<212> DNA
<213> 猪流感病毒
<400> 34
atgaagacta tcattgcttt tagctgcgtt ttatgtttga ttttcgctca aaaacttccc 60
ggaagtgaca acagcatggc aacgctgtgc ctgggacacc atgcagtacc aaacggaacg 120
ttagtgaaaa caatcacgga tgaccaaatt gaagtgacta atgctactga gctggttcag 180
agttcctcaa caggtagaat atgcaacagt cctcaccaaa tccttgatgg gaaaaattgc 240
acactgatag atgctctatt gggagaccct cattgtgatg acttccaaaa caaggaatgg 300
gacctttttg ttgaacgaag cacagcctac agcaactgtt acccttatta tgtgccggat 360
tatgcctccc ttaggtcact agttgcatca tccggcaccc tggaatttac ccaagaaagc 420
ttcaattgga ctggagttgc tcaagatgga tcaagctatg cttgcagaag ggaatctgtt 480
aacagtttct ttagtagatt gaattggttg cataaattgg attacaaata tccagcgctg 540
aaagtaacta tgccgaacaa tgacaaattc gacaaattgt acatttgggg ggttcaccac 600
ccgggcactg acagggacca aaccaaccta tatgttcaaa catcagggag agttacagtc 660
tccaccaaaa gaagccaaca aactgtaatc ccaaatatcg ggtctagacc ctgggtaagg 720
ggtgtctcca gcataataag catctattgg acaatagtaa aaccgggaga catacttttg 780
attaacagca cagggaatct aattgcccct cggggttact tcaaattaca aagtgggaaa 840
agctcaataa tgagatcaga tgcacccatt ggcatctgca attctgaatg cattactcca 900
aatggaagca ttcccaacga caaacctttt caaaatgtaa acaggatcac ttatggggcc 960
tgtcccagat atgttaagca aaacaccctg aaattggcaa caggaatgcg gaatgtacca 1020
gagaaacaaa ccagaggcat atttggcgca atcgcaggtt tcatagaaaa tggttgggaa 1080
gggatggtgg acggttggta cggtttcagg catcaaaatt ctgaaggcac aggacaagca 1140
gcagatctta aaagcactcg tgcagcaatc aaccaaatca ccgggaaact aaatagagta 1200
atcaagaaaa cgaacgagaa attccatcag atcgaaaaag aattctcaga agtagaaggg 1260
agaattcagg acctagagaa atacgttgaa gacactaaaa tagacctctg gtcttacaac 1320
gcggagcttc ttgttgccct ggagaaccaa cacacaattg atttaactga ctcagaaatg 1380
aacaaactgt tcgaaagaac aagaaagcaa ttgcgggaaa atgctgagga catgggcaat 1440
ggttgcttca aaatatacca caaatgtgac aatgcctgca taggatcaat cagaaatgga 1500
acttatgacc atgatgtata cagagatgag gcattaaaca atcggttcca gatcaaaggt 1560
gttcagctga agtcaggata caaagattgg atcctatgga tttcctttgc catatcatgc 1620
tttttgcttt gtgttgttct gctggggttc attatgtggg cctgccaaaa aggcaacatt 1680
aggtgcaaca tttgcatt 1698
<210> 35
<211> 1698
<212> DNA
<213> 人工序列
<220>
<223> HA-DO (H3N2; 去优化的)
<400> 35
atgaagacta tcattgcttt tagctgcgtt ttatgtttga ttttcgctca aaaacttccc 60
ggaagtgaca acagcatggc aacgctgtgc ttaggacatc atgcggtccc gaatggaacg 120
ttagtcaaaa cgataacgga tgatcaaata gaagtcacga atgcgacgga attagtccaa 180
tcgtcgtcga cgggacgtat atgtaattcg ccgcatcaaa tattagatgg aaaaaattgt 240
acgttaatag atgcgttatt aggagatccg cattgtgatg attttcaaaa taaagaatgg 300
gatttatttg tcgaacgttc gacggcgtat tcgaattgtt atccgtatta tgtcccggat 360
tatgcgtcgt tacgttcgtt agtcgcgtcg tcgggaacgt tagaatttac gcaagaatcg 420
tttaattgga cgggagtcgc gcaagatgga tcgtcgtatg cgtgtcgtcg tgaatcggtc 480
aattcgtttt tttcgcgttt aaattggtta cataaattag attataaata tccggcgtta 540
aaagtcacga tgccgaataa tgataaattt gataaattat atatatgggg agtccatcat 600
ccgggaacgg atcgtgatca aacgaattta tatgtccaaa cgtcgggacg tgtcacggtc 660
tcgacgaaac gttcgcaaca aacggtcata ccgaatatag gatcgcgtcc gtgggtccgt 720
ggagtctcgt cgataatatc gatatattgg acgatagtca aaccgggaga tatattatta 780
ataaattcga cgggaaattt aatagcgccg cgtggatatt ttaaattaca atcgggaaaa 840
tcgtcgataa tgcgttcgga tgcgccgata ggaatatgta attcggaatg tataacgccg 900
aatggatcga taccgaatga taaaccgttt caaaatgtca atcgtataac ctatggagcg 960
tgtccgcgtt atgtcaaaca aaatacgtta aaattagcga cgggaatgcg taatgtcccg 1020
gaaaaacaaa cgcgtggaat atttggagcg atagcgggat ttatagaaaa tggatgggaa 1080
ggaatggtcg atggatggta tggatttcgt catcaaaatt cggaaggaac gggacaagcg 1140
gcggatttaa aatcgacgcg tgcggcgata aatcaaataa cgggaaaatt aaatcgtgtc 1200
ataaaaaaaa cgaatgaaaa atttcatcaa atagaaaaag aattttcgga agtcgaagga 1260
cgtatacaag atttagaaaa atatgtcgaa gatacgaaaa tagatttatg gtcgtataat 1320
gcggaattat tagtcgcgtt agaaaatcaa catacgatag atttaacgga ttcggaaatg 1380
aataaattat ttgaacgtac gcgtaaacaa ttacgtgaaa atgcggaaga tatgggaaat 1440
ggatgtttta aaatatatca taaatgtgat aatgcgtgta taggatcgat acgtaatgga 1500
acgtatgatc atgatgtcta tcgtgatgaa gcgttaaata atcgttttca aataaaagga 1560
gtccaattaa aatcgggata taaagattgg atattatgga tatcgtttgc gatatcgtgc 1620
tttttgcttt gtgttgttct gctggggttc attatgtggg cctgccaaaa aggcaacatt 1680
aggtgcaaca tttgcatt 1698
<210> 36
<211> 566
<212> PRT
<213> 猪流感病毒
<400> 36
Met Lys Thr Ile Ile Ala Phe Ser Cys Val Leu Cys Leu Ile Phe Ala
1 5 10 15
Gln Lys Leu Pro Gly Ser Asp Asn Ser Met Ala Thr Leu Cys Leu Gly
20 25 30
His His Ala Val Pro Asn Gly Thr Leu Val Lys Thr Ile Thr Asp Asp
35 40 45
Gln Ile Glu Val Thr Asn Ala Thr Glu Leu Val Gln Ser Ser Ser Thr
50 55 60
Gly Arg Ile Cys Asn Ser Pro His Gln Ile Leu Asp Gly Lys Asn Cys
65 70 75 80
Thr Leu Ile Asp Ala Leu Leu Gly Asp Pro His Cys Asp Asp Phe Gln
85 90 95
Asn Lys Glu Trp Asp Leu Phe Val Glu Arg Ser Thr Ala Tyr Ser Asn
100 105 110
Cys Tyr Pro Tyr Tyr Val Pro Asp Tyr Ala Ser Leu Arg Ser Leu Val
115 120 125
Ala Ser Ser Gly Thr Leu Glu Phe Thr Gln Glu Ser Phe Asn Trp Thr
130 135 140
Gly Val Ala Gln Asp Gly Ser Ser Tyr Ala Cys Arg Arg Glu Ser Val
145 150 155 160
Asn Ser Phe Phe Ser Arg Leu Asn Trp Leu His Lys Leu Asp Tyr Lys
165 170 175
Tyr Pro Ala Leu Lys Val Thr Met Pro Asn Asn Asp Lys Phe Asp Lys
180 185 190
Leu Tyr Ile Trp Gly Val His His Pro Gly Thr Asp Arg Asp Gln Thr
195 200 205
Asn Leu Tyr Val Gln Thr Ser Gly Arg Val Thr Val Ser Thr Lys Arg
210 215 220
Ser Gln Gln Thr Val Ile Pro Asn Ile Gly Ser Arg Pro Trp Val Arg
225 230 235 240
Gly Val Ser Ser Ile Ile Ser Ile Tyr Trp Thr Ile Val Lys Pro Gly
245 250 255
Asp Ile Leu Leu Ile Asn Ser Thr Gly Asn Leu Ile Ala Pro Arg Gly
260 265 270
Tyr Phe Lys Leu Gln Ser Gly Lys Ser Ser Ile Met Arg Ser Asp Ala
275 280 285
Pro Ile Gly Ile Cys Asn Ser Glu Cys Ile Thr Pro Asn Gly Ser Ile
290 295 300
Pro Asn Asp Lys Pro Phe Gln Asn Val Asn Arg Ile Thr Tyr Gly Ala
305 310 315 320
Cys Pro Arg Tyr Val Lys Gln Asn Thr Leu Lys Leu Ala Thr Gly Met
325 330 335
Arg Asn Val Pro Glu Lys Gln Thr Arg Gly Ile Phe Gly Ala Ile Ala
340 345 350
Gly Phe Ile Glu Asn Gly Trp Glu Gly Met Val Asp Gly Trp Tyr Gly
355 360 365
Phe Arg His Gln Asn Ser Glu Gly Thr Gly Gln Ala Ala Asp Leu Lys
370 375 380
Ser Thr Arg Ala Ala Ile Asn Gln Ile Thr Gly Lys Leu Asn Arg Val
385 390 395 400
Ile Lys Lys Thr Asn Glu Lys Phe His Gln Ile Glu Lys Glu Phe Ser
405 410 415
Glu Val Glu Gly Arg Ile Gln Asp Leu Glu Lys Tyr Val Glu Asp Thr
420 425 430
Lys Ile Asp Leu Trp Ser Tyr Asn Ala Glu Leu Leu Val Ala Leu Glu
435 440 445
Asn Gln His Thr Ile Asp Leu Thr Asp Ser Glu Met Asn Lys Leu Phe
450 455 460
Glu Arg Thr Arg Lys Gln Leu Arg Glu Asn Ala Glu Asp Met Gly Asn
465 470 475 480
Gly Cys Phe Lys Ile Tyr His Lys Cys Asp Asn Ala Cys Ile Gly Ser
485 490 495
Ile Arg Asn Gly Thr Tyr Asp His Asp Val Tyr Arg Asp Glu Ala Leu
500 505 510
Asn Asn Arg Phe Gln Ile Lys Gly Val Gln Leu Lys Ser Gly Tyr Lys
515 520 525
Asp Trp Ile Leu Trp Ile Ser Phe Ala Ile Ser Cys Phe Leu Leu Cys
530 535 540
Val Val Leu Leu Gly Phe Ile Met Trp Ala Cys Gln Lys Gly Asn Ile
545 550 555 560
Arg Cys Asn Ile Cys Ile
565
<210> 37
<211> 1407
<212> DNA
<213> 猪流感病毒
<400> 37
atgaatccaa atcaaaagat aataacaatt ggctctgttt ctctcctcat tgccacaata 60
tgcttcctta tgcaaattgc catcctggta actactgtaa cattgcattt caagcagcat 120
gattgcaact cctccccaaa caaccaagta atgctgtgtg aaccaacaat aatagaaaga 180
aacacaacag agattgtgta tctgaccaac ataactatag agaaggaaat atgccccaaa 240
ctagcagaat acagaaattg gtcaaagcct caatgtaaca ttacaggatt tgcacctttc 300
tctaaggaca attcgattcg gctttccgct ggcggggaca tctgggtgac aagagaacct 360
tatgtgtcgt gcgatcctga caagtgttat caatttgccc ttgggcaggg aacaacacta 420
aacaacggtc attcaaatga cactgtacat gataggaccc cttaccgaac cctattgatg 480
aatgaattgg gtgttccatt tcatttgggg accaggcaag tgtgcatagc atggtccagc 540
tcaagttgtc acgatggaaa agcatggttg catgtttgta taactgggga tgataaaaat 600
gcaactgcta gcttcattta caatgggagg cttgtagata gtattggttc atggtccaaa 660
aatatactca gaacccagga gtcggaatgc gtttgtatca atggaacttg tacagtagta 720
atgactgatg ggagcgcttc aggaaaagct gatactaaag tactattcat tgaggaggga 780
aaaatcgttc atattagcac attgtcagga agtgctcagc atgtcgagga gtgctcctgt 840
tatcctcgat atcctggtgt cagatgtgtc tgtagagaca actggaaagg ctccaacagg 900
cccatcgtag acataaatgt aaaggattat agtattgttt ccagttatgt atgctcagga 960
cttgttggag acacacccag aaaaaacgac agattcagca gtagccattg ccaagatcct 1020
aacaatgagg aaggaggtca tggggtgaaa ggctgggcct ttgatgatgg aaatgacgtg 1080
tggatgggaa gaacgatcaa cgagaaatta cgctcaggtt atgaaacctt caaagtcatc 1140
gaaggctggt ccaaacctaa ctccaaatta cagacaaata ggcaagtcat agttgaaaga 1200
ggtaacaggt ccggttattc tggtattttc tccgttgaag gcaaaagctg catcaatcgg 1260
tgtttttatg tggagttgat aaggggaagg aaagaggaaa ctaaagtctg gtggacctca 1320
aacagtattg ttgtgctttg tggcacctca ggtacatatg gaacaggctc atggcctgat 1380
ggggcggata tcaatctcat gcctata 1407
<210> 38
<211> 1407
<212> DNA
<213> 人工序列
<220>
<223> NA-DO (H3N2; 去优化的)
<400> 38
atgaatccaa atcaaaagat aataacaatt ggctctgttt ctctcctcat tgccacaata 60
tgcttcctta tgcaaattgc catcctggta actactgtaa cattgcattt caaacaacat 120
gattgtaatt cgtcgccgaa taatcaagtc atgttatgtg aaccgacgat aatagaacgt 180
aatacgacgg aaatagtcta tttaacgaat ataacgatag aaaaagaaat atgtccgaaa 240
ttagcggaat atcgtaattg gtcgaaaccg caatgtaata taacgggatt tgcgccgttt 300
tcgaaagata attcgatacg tttatcggcg ggaggagata tatgggtcac gcgtgaaccg 360
tatgtctcgt gtgatccgga taaatgttat caatttgcgt taggacaagg aacgacgtta 420
aataatggac attcgaatga tacggtccat gatcgtacgc cgtatcgcac gttattaatg 480
aatgaattag gagtcccgtt tcatttagga acgcgtcaag tctgtatagc gtggtcgtcg 540
tcgtcgtgtc atgatggaaa agcgtggtta catgtctgta taacgggaga tgataaaaat 600
gcgacggcgt cgtttatata taatggacgt ttagtcgatt cgataggatc gtggtcgaaa 660
aatatattac gtacgcaaga atcggaatgt gtctgtataa atggaacgtg tacggtcgtc 720
atgacggatg gatcggcgtc gggaaaagcg gatacgaaag tcttatttat agaagaagga 780
aaaatagtcc atatatcgac gttatcggga tcggcgcaac atgtcgaaga atgttcgtgt 840
tatccgcgtt atccgggagt ccgttgtgtc tgtcgtgata attggaaagg atcgaatcgt 900
ccgatagtcg atataaatgt caaagattat tcgatagtct cgtcgtatgt ctgttcggga 960
ttagtcggag atacgccgcg taaaaatgat cgtttttcgt cgtcgcattg tcaagatccg 1020
aataatgaag aaggaggaca tggagtcaaa ggatgggcgt ttgatgatgg aaatgatgtc 1080
tggatgggac gtacgataaa tgaaaaatta cgttcgggat atgaaacgtt taaagtcata 1140
gaaggatggt cgaaaccgaa ttcgaaatta caaacgaatc gtcaagtcat agtcgaacgt 1200
ggaaatcgtt cgggatattc gggaatattt tcggtcgaag gaaaatcgtg tataaatcgt 1260
tgtttttatg tcgaattaat acgtggacgt aaagaagaaa ctaaagtctg gtggacctca 1320
aacagtattg ttgtgctttg tggcacctca ggtacatatg gaacaggctc atggcctgat 1380
ggggcggata tcaatctcat gcctata 1407
<210> 39
<211> 469
<212> PRT
<213> 猪流感病毒
<400> 39
Met Asn Pro Asn Gln Lys Ile Ile Thr Ile Gly Ser Val Ser Leu Leu
1 5 10 15
Ile Ala Thr Ile Cys Phe Leu Met Gln Ile Ala Ile Leu Val Thr Thr
20 25 30
Val Thr Leu His Phe Lys Gln His Asp Cys Asn Ser Ser Pro Asn Asn
35 40 45
Gln Val Met Leu Cys Glu Pro Thr Ile Ile Glu Arg Asn Thr Thr Glu
50 55 60
Ile Val Tyr Leu Thr Asn Ile Thr Ile Glu Lys Glu Ile Cys Pro Lys
65 70 75 80
Leu Ala Glu Tyr Arg Asn Trp Ser Lys Pro Gln Cys Asn Ile Thr Gly
85 90 95
Phe Ala Pro Phe Ser Lys Asp Asn Ser Ile Arg Leu Ser Ala Gly Gly
100 105 110
Asp Ile Trp Val Thr Arg Glu Pro Tyr Val Ser Cys Asp Pro Asp Lys
115 120 125
Cys Tyr Gln Phe Ala Leu Gly Gln Gly Thr Thr Leu Asn Asn Gly His
130 135 140
Ser Asn Asp Thr Val His Asp Arg Thr Pro Tyr Arg Thr Leu Leu Met
145 150 155 160
Asn Glu Leu Gly Val Pro Phe His Leu Gly Thr Arg Gln Val Cys Ile
165 170 175
Ala Trp Ser Ser Ser Ser Cys His Asp Gly Lys Ala Trp Leu His Val
180 185 190
Cys Ile Thr Gly Asp Asp Lys Asn Ala Thr Ala Ser Phe Ile Tyr Asn
195 200 205
Gly Arg Leu Val Asp Ser Ile Gly Ser Trp Ser Lys Asn Ile Leu Arg
210 215 220
Thr Gln Glu Ser Glu Cys Val Cys Ile Asn Gly Thr Cys Thr Val Val
225 230 235 240
Met Thr Asp Gly Ser Ala Ser Gly Lys Ala Asp Thr Lys Val Leu Phe
245 250 255
Ile Glu Glu Gly Lys Ile Val His Ile Ser Thr Leu Ser Gly Ser Ala
260 265 270
Gln His Val Glu Glu Cys Ser Cys Tyr Pro Arg Tyr Pro Gly Val Arg
275 280 285
Cys Val Cys Arg Asp Asn Trp Lys Gly Ser Asn Arg Pro Ile Val Asp
290 295 300
Ile Asn Val Lys Asp Tyr Ser Ile Val Ser Ser Tyr Val Cys Ser Gly
305 310 315 320
Leu Val Gly Asp Thr Pro Arg Lys Asn Asp Arg Phe Ser Ser Ser His
325 330 335
Cys Gln Asp Pro Asn Asn Glu Glu Gly Gly His Gly Val Lys Gly Trp
340 345 350
Ala Phe Asp Asp Gly Asn Asp Val Trp Met Gly Arg Thr Ile Asn Glu
355 360 365
Lys Leu Arg Ser Gly Tyr Glu Thr Phe Lys Val Ile Glu Gly Trp Ser
370 375 380
Lys Pro Asn Ser Lys Leu Gln Thr Asn Arg Gln Val Ile Val Glu Arg
385 390 395 400
Gly Asn Arg Ser Gly Tyr Ser Gly Ile Phe Ser Val Glu Gly Lys Ser
405 410 415
Cys Ile Asn Arg Cys Phe Tyr Val Glu Leu Ile Arg Gly Arg Lys Glu
420 425 430
Glu Thr Lys Val Trp Trp Thr Ser Asn Ser Ile Val Val Leu Cys Gly
435 440 445
Thr Ser Gly Thr Tyr Gly Thr Gly Ser Trp Pro Asp Gly Ala Asp Ile
450 455 460
Asn Leu Met Pro Ile
465
<210> 40
<211> 363
<212> DNA
<213> 猪流感病毒
<400> 40
atggactcca acactgtgtc aagctttcag gacatactga agaggatgtc aaaaatgcag 60
ttggggtcct catcggagga cttgaatgga atggtaacac ggttcgagtc cctgaaaatc 120
tacagagatt cgcttggaga aaccgtaatg aggatgggag accttcacta cctccagagc 180
agaaatgaaa aatggcgaga gcaattggga cagaaatttg aggaaattag gtggttaatt 240
gaagaagtgc ggcacagatt gaaagcgaca gagaatagtt tcgaacaaat aacatttatg 300
caagccttac aactactgct tgaagtagaa caagagataa gaactttctc gtttcagctt 360
att 363
<210> 41
<211> 121
<212> PRT
<213> 猪流感病毒
<400> 41
Met Asp Ser Asn Thr Val Ser Ser Phe Gln Asp Ile Leu Lys Arg Met
1 5 10 15
Ser Lys Met Gln Leu Gly Ser Ser Ser Glu Asp Leu Asn Gly Met Val
20 25 30
Thr Arg Phe Glu Ser Leu Lys Ile Tyr Arg Asp Ser Leu Gly Glu Thr
35 40 45
Val Met Arg Met Gly Asp Leu His Tyr Leu Gln Ser Arg Asn Glu Lys
50 55 60
Trp Arg Glu Gln Leu Gly Gln Lys Phe Glu Glu Ile Arg Trp Leu Ile
65 70 75 80
Glu Glu Val Arg His Arg Leu Lys Ala Thr Glu Asn Ser Phe Glu Gln
85 90 95
Ile Thr Phe Met Gln Ala Leu Gln Leu Leu Leu Glu Val Glu Gln Glu
100 105 110
Ile Arg Thr Phe Ser Phe Gln Leu Ile
115 120
<210> 42
<211> 657
<212> DNA
<213> 猪流感病毒
<400> 42
atggactcca acactgtgtc aagctttcag gtagactgtt tcctttggca tatccgcaaa 60
cggtttgcag acaatggatt gggtgatgcc ccattccttg atcggctccg ccgagatcaa 120
aagtccctaa aaggaagagg caacaccctt ggcctcgaca tcgaaacagc cactcttgtt 180
gggaaacaaa ttgtggagtg gattttgaaa gaggaatcca gcgagacact taagatgacc 240
attgcatctg tacctacttc gcgctactta gctgacatga ccctcgagga aatgtcacga 300
gactggttca tgctcatgcc taggcaaaag ataataggct ctctttgtgt gcgaatggac 360
caggcgatca tggaaaagaa catcatactg aaagcgaact tcagtgtgat cttcaaccga 420
ttagagactt tgatactact aagggctttc actgaggagg gagcaatcgt tggagaaatt 480
tcaccattac cttctcttcc aggacatact gaagaggatg tcaaaaatgc agttggggtc 540
ctcatcggag gacttgaatg gaatggtaac acggttcgag tccctgaaaa tctacagaga 600
ttcgcttgga gaaaccgtaa tgaggatggg agaccttcac tacctccaga gcagaaa 657
<210> 43
<211> 219
<212> PRT
<213> 猪流感病毒
<400> 43
Met Asp Ser Asn Thr Val Ser Ser Phe Gln Val Asp Cys Phe Leu Trp
1 5 10 15
His Ile Arg Lys Arg Phe Ala Asp Asn Gly Leu Gly Asp Ala Pro Phe
20 25 30
Leu Asp Arg Leu Arg Arg Asp Gln Lys Ser Leu Lys Gly Arg Gly Asn
35 40 45
Thr Leu Gly Leu Asp Ile Glu Thr Ala Thr Leu Val Gly Lys Gln Ile
50 55 60
Val Glu Trp Ile Leu Lys Glu Glu Ser Ser Glu Thr Leu Lys Met Thr
65 70 75 80
Ile Ala Ser Val Pro Thr Ser Arg Tyr Leu Ala Asp Met Thr Leu Glu
85 90 95
Glu Met Ser Arg Asp Trp Phe Met Leu Met Pro Arg Gln Lys Ile Ile
100 105 110
Gly Ser Leu Cys Val Arg Met Asp Gln Ala Ile Met Glu Lys Asn Ile
115 120 125
Ile Leu Lys Ala Asn Phe Ser Val Ile Phe Asn Arg Leu Glu Thr Leu
130 135 140
Ile Leu Leu Arg Ala Phe Thr Glu Glu Gly Ala Ile Val Gly Glu Ile
145 150 155 160
Ser Pro Leu Pro Ser Leu Pro Gly His Thr Glu Glu Asp Val Lys Asn
165 170 175
Ala Val Gly Val Leu Ile Gly Gly Leu Glu Trp Asn Gly Asn Thr Val
180 185 190
Arg Val Pro Glu Asn Leu Gln Arg Phe Ala Trp Arg Asn Arg Asn Glu
195 200 205
Asp Gly Arg Pro Ser Leu Pro Pro Glu Gln Lys
210 215
<210> 44
<211> 756
<212> DNA
<213> 猪流感病毒
<400> 44
atgagtcttc taaccgaggt cgaaacgtat gttctctcta tcgttccgtc aggccccctc 60
aaagccgaga tagcacagag actcgaagac gtttttgcag ggaaaaacac cgatcttgag 120
gctctcatgg aatggctaaa gacaagacca atcctgtcac ctctgactaa ggggatttta 180
gggtttgtgt tcacgctcac cgtgcccagt gagcgaggac tgcagcgtag acgctttgtc 240
cagaatgccc tcaatgggaa tggtgacccg aacaacatgg acaaagcagt caaactgtac 300
aggaaactca aaagggaaat aacattccat ggggccaaag aagtagcgct cagttactct 360
gctggtgcgc ttgccagttg catgggtctc atatacaaca gaatggggac tgtcaccact 420
gaggtggcct ttggtctagt atgcgcaacc tgtgaacaga ttgctgattc ccagcatcga 480
tctcatagac aaatggtgac aacaaccaat ccactaatca ggcacgagaa cagaatggtg 540
atagccagca caacagctaa agccatggaa caaatggctg gatcaagcga acaagcagca 600
gaggctatgg aggttgccag ccaggctaga caaatggtac aggcaatgag aacaattggg 660
actcacccta gttccagcgc tggtctaaaa gatgatcttc ttgaaaattt acaggcctat 720
cagaaacgga tgggagtgca aatgcaacga ttcaag 756
<210> 45
<211> 252
<212> PRT
<213> 猪流感病毒
<400> 45
Met Ser Leu Leu Thr Glu Val Glu Thr Tyr Val Leu Ser Ile Val Pro
1 5 10 15
Ser Gly Pro Leu Lys Ala Glu Ile Ala Gln Arg Leu Glu Asp Val Phe
20 25 30
Ala Gly Lys Asn Thr Asp Leu Glu Ala Leu Met Glu Trp Leu Lys Thr
35 40 45
Arg Pro Ile Leu Ser Pro Leu Thr Lys Gly Ile Leu Gly Phe Val Phe
50 55 60
Thr Leu Thr Val Pro Ser Glu Arg Gly Leu Gln Arg Arg Arg Phe Val
65 70 75 80
Gln Asn Ala Leu Asn Gly Asn Gly Asp Pro Asn Asn Met Asp Lys Ala
85 90 95
Val Lys Leu Tyr Arg Lys Leu Lys Arg Glu Ile Thr Phe His Gly Ala
100 105 110
Lys Glu Val Ala Leu Ser Tyr Ser Ala Gly Ala Leu Ala Ser Cys Met
115 120 125
Gly Leu Ile Tyr Asn Arg Met Gly Thr Val Thr Thr Glu Val Ala Phe
130 135 140
Gly Leu Val Cys Ala Thr Cys Glu Gln Ile Ala Asp Ser Gln His Arg
145 150 155 160
Ser His Arg Gln Met Val Thr Thr Thr Asn Pro Leu Ile Arg His Glu
165 170 175
Asn Arg Met Val Ile Ala Ser Thr Thr Ala Lys Ala Met Glu Gln Met
180 185 190
Ala Gly Ser Ser Glu Gln Ala Ala Glu Ala Met Glu Val Ala Ser Gln
195 200 205
Ala Arg Gln Met Val Gln Ala Met Arg Thr Ile Gly Thr His Pro Ser
210 215 220
Ser Ser Ala Gly Leu Lys Asp Asp Leu Leu Glu Asn Leu Gln Ala Tyr
225 230 235 240
Gln Lys Arg Met Gly Val Gln Met Gln Arg Phe Lys
245 250
<210> 46
<211> 1407
<212> DNA
<213> 猪流感病毒
<400> 46
atgaatccaa atcaaaagat aataacgatt ggctctgtct ctctcactat tgccacaatg 60
tgcctcctta tgcaaattgc catcctggta actactgtaa cattgcattt caagcaatat 120
gaatgcaact cccccccaaa caaccaagta atactgtgtg aaccaacaat aatagaaaga 180
aacataacag agatagtgta tctgaccaac accaccatag agaaggaaat gtgccccaag 240
ctagcagaat acagaagttg gtcaaagccg caatgtaaaa ttacaggatt tgcacctttt 300
tccaaggaca attcgattag gctttccgct ggtggggaca tttgggtgac aagagaacct 360
tatgtgtcat gcgatcctga caagtgttac caatttgccc ttggacaggg aacaacacta 420
aacaacaggc attcaaatga cacagtacat gataggaccc cttatcgaac cctattgatg 480
aatgagttgg gtgttccatt tcatttggga accaagcaag tgtgcatagc atggtccagc 540
tcaagttgtc atgatggaaa agcatggctg catgtttgtg taactgggca tgatgaaaat 600
gcaactgcta gcttcattta cgatgggagg ctggtagata gtattggttc atggaccaaa 660
aaaatcctca ggacccatga gtcggaatgc gtttgtatca atggaacttg tacagtagta 720
atgactgatg ggagtgcttc aggaagagct gatactaaaa tattattcat tgaggagggg 780
aaaatcgttc atattagccc attgttggga agtgctcagc atgttgagga gtgctcctgt 840
tatcctcgat atcctggtgt cagatgtgtc tgcagagaca actggaaagg ctccaatagg 900
cccgtcgtag atataaatgt aaaggattat agcattgttt ccagttatgt gtgctcagga 960
cttgttggag acacacccag aaaaaacgac agatccagca gtagcagttg cctgaatcct 1020
accaatgagg aagggggtca tggagtgaaa ggctgggcct ttgatgatgg aaatgacgtg 1080
tggatgggaa gaacgatcag cgagaaatta cgctcaggtt atgaaacctt caaagtcatt 1140
gaaggctggt ccaaacccaa ctccaaattg cagataaata ggcaagtcat agttgacaga 1200
ggtgataggt ccggttattc tggcattttc tctgttgaag gcaaaagctg catcaatcgg 1260
tgcttttatg tggagttgat aaggggaagg aaacaggaaa ctgaagtatg gtggacctca 1320
aacagtattg ttgtgttttg tggcacctca ggtacatatg gaacaggctc atggcctgat 1380
ggggcggaca tcaatctcat gcctata 1407
<210> 47
<211> 469
<212> PRT
<213> 猪流感病毒
<400> 47
Met Asn Pro Asn Gln Lys Ile Ile Thr Ile Gly Ser Val Ser Leu Thr
1 5 10 15
Ile Ala Thr Met Cys Leu Leu Met Gln Ile Ala Ile Leu Val Thr Thr
20 25 30
Val Thr Leu His Phe Lys Gln Tyr Glu Cys Asn Ser Pro Pro Asn Asn
35 40 45
Gln Val Ile Leu Cys Glu Pro Thr Ile Ile Glu Arg Asn Ile Thr Glu
50 55 60
Ile Val Tyr Leu Thr Asn Thr Thr Ile Glu Lys Glu Met Cys Pro Lys
65 70 75 80
Leu Ala Glu Tyr Arg Ser Trp Ser Lys Pro Gln Cys Lys Ile Thr Gly
85 90 95
Phe Ala Pro Phe Ser Lys Asp Asn Ser Ile Arg Leu Ser Ala Gly Gly
100 105 110
Asp Ile Trp Val Thr Arg Glu Pro Tyr Val Ser Cys Asp Pro Asp Lys
115 120 125
Cys Tyr Gln Phe Ala Leu Gly Gln Gly Thr Thr Leu Asn Asn Arg His
130 135 140
Ser Asn Asp Thr Val His Asp Arg Thr Pro Tyr Arg Thr Leu Leu Met
145 150 155 160
Asn Glu Leu Gly Val Pro Phe His Leu Gly Thr Lys Gln Val Cys Ile
165 170 175
Ala Trp Ser Ser Ser Ser Cys His Asp Gly Lys Ala Trp Leu His Val
180 185 190
Cys Val Thr Gly His Asp Glu Asn Ala Thr Ala Ser Phe Ile Tyr Asp
195 200 205
Gly Arg Leu Val Asp Ser Ile Gly Ser Trp Thr Lys Lys Ile Leu Arg
210 215 220
Thr His Glu Ser Glu Cys Val Cys Ile Asn Gly Thr Cys Thr Val Val
225 230 235 240
Met Thr Asp Gly Ser Ala Ser Gly Arg Ala Asp Thr Lys Ile Leu Phe
245 250 255
Ile Glu Glu Gly Lys Ile Val His Ile Ser Pro Leu Leu Gly Ser Ala
260 265 270
Gln His Val Glu Glu Cys Ser Cys Tyr Pro Arg Tyr Pro Gly Val Arg
275 280 285
Cys Val Cys Arg Asp Asn Trp Lys Gly Ser Asn Arg Pro Val Val Asp
290 295 300
Ile Asn Val Lys Asp Tyr Ser Ile Val Ser Ser Tyr Val Cys Ser Gly
305 310 315 320
Leu Val Gly Asp Thr Pro Arg Lys Asn Asp Arg Ser Ser Ser Ser Ser
325 330 335
Cys Leu Asn Pro Thr Asn Glu Glu Gly Gly His Gly Val Lys Gly Trp
340 345 350
Ala Phe Asp Asp Gly Asn Asp Val Trp Met Gly Arg Thr Ile Ser Glu
355 360 365
Lys Leu Arg Ser Gly Tyr Glu Thr Phe Lys Val Ile Glu Gly Trp Ser
370 375 380
Lys Pro Asn Ser Lys Leu Gln Ile Asn Arg Gln Val Ile Val Asp Arg
385 390 395 400
Gly Asp Arg Ser Gly Tyr Ser Gly Ile Phe Ser Val Glu Gly Lys Ser
405 410 415
Cys Ile Asn Arg Cys Phe Tyr Val Glu Leu Ile Arg Gly Arg Lys Gln
420 425 430
Glu Thr Glu Val Trp Trp Thr Ser Asn Ser Ile Val Val Phe Cys Gly
435 440 445
Thr Ser Gly Thr Tyr Gly Thr Gly Ser Trp Pro Asp Gly Ala Asp Ile
450 455 460
Asn Leu Met Pro Ile
465
<210> 48
<211> 1512
<212> DNA
<213> 猪流感病毒
<400> 48
atgagtgaca tcgaagccat ggcgtctcaa ggcaccaaac gatcatatga acagatggag 60
actggtgggg aacgccagga tgccacagaa atcagagcat ctgtcggaag aatgattggt 120
ggaatcggga gattctacat ccaaatgtgc actgaactca aactcagtga ctatgaggga 180
cgactaatcc aaaatagcat aacaatagag agaatggtgc tctctgcttt tgatgagaga 240
agaaataagt acctagaaga gcatcccagt gctgggaagg atcctaagaa aactggagga 300
cccatatata gaagagtaga cggaaagtgg atgagagaac tcatccttta tgacaaagaa 360
gaaataagga gagtttggcg ccaagcaaac aatggtgaag atgcaacagc tggtcttact 420
catatcatga tttggcattc caatctgaat gatgccacgt atcagagaac aagagcactt 480
gttcgcaccg gaatggatcc cagaatgtgc tctctgatgc aaggttcaac acttcccaga 540
aggtctgggg ccgcaggtgc tgcagtgaaa ggagttggaa caatagcaat ggagttaatc 600
agaatgatca aacgtggaat caatgaccga aacttctgga ggggtgaaaa tggacgaagg 660
acaaggactg catatgaaag gatgtgcaat attctcaaag gaaaatttca gacagctgcc 720
cagagagcaa tgatggatca agtgagagaa agtcggaacc caggaaacgc tgagattgaa 780
gatctcattt tcctggcacg gtcagcactt attctaaggg gatcagttgc acataagtct 840
tgcctgcctg cttgtgtgta tgggcttgca gtagcaagtg ggcatgactt tgaaagggaa 900
gggtattcac tggttgggat agacccattt aaattacttc aaaacagtca agtgttcagc 960
ctgataagac caaatgaaaa cccagctcac aagagtcaat tggtgtggat ggcatgccac 1020
tctgctgcat ttgaggattt gagagtatca agtttcataa gggggaagaa ggtgattcca 1080
agaggaaagc tttccacaag aggggttcag attgcttcaa atgaaaatgt ggaagccatg 1140
gactccaata ccctagaact gagaagcaga tactgggcca taaggaccag gagtggagga 1200
aataccaatc aacagaaggc atccgcgggc cagatcagtg tgcaacctac attctcagta 1260
caacggaacc tcccttttga aagagcaacc gttttggcag ctttcagcgg gaacaatgaa 1320
ggacggacat ccgatatgcg aacagaagtt ataaggatga tggaaagtgc aaagccagaa 1380
gatttgtcct tccaggggcg gggagtcttc gagctctcgg acgaaaaggc aacgagcccg 1440
atcgtgcctt cctttgacat gagtaatgaa gggtcttatt tcttcggaga caatgcagag 1500
gagtatgaca gt 1512
<210> 49
<211> 498
<212> PRT
<213> 猪流感病毒
<400> 49
Met Ala Ser Gln Gly Thr Lys Arg Ser Tyr Glu Gln Met Glu Thr Gly
1 5 10 15
Gly Glu Arg Gln Asp Ala Thr Glu Ile Arg Ala Ser Val Gly Arg Met
20 25 30
Ile Gly Gly Ile Gly Arg Phe Tyr Ile Gln Met Cys Thr Glu Leu Lys
35 40 45
Leu Ser Asp Tyr Glu Gly Arg Leu Ile Gln Asn Ser Ile Thr Ile Glu
50 55 60
Arg Met Val Leu Ser Ala Phe Asp Glu Arg Arg Asn Lys Tyr Leu Glu
65 70 75 80
Glu His Pro Ser Ala Gly Lys Asp Pro Lys Lys Thr Gly Gly Pro Ile
85 90 95
Tyr Arg Arg Val Asp Gly Lys Trp Met Arg Glu Leu Ile Leu Tyr Asp
100 105 110
Lys Glu Glu Ile Arg Arg Val Trp Arg Gln Ala Asn Asn Gly Glu Asp
115 120 125
Ala Thr Ala Gly Leu Thr His Ile Met Ile Trp His Ser Asn Leu Asn
130 135 140
Asp Ala Thr Tyr Gln Arg Thr Arg Ala Leu Val Arg Thr Gly Met Asp
145 150 155 160
Pro Arg Met Cys Ser Leu Met Gln Gly Ser Thr Leu Pro Arg Arg Ser
165 170 175
Gly Ala Ala Gly Ala Ala Val Lys Gly Val Gly Thr Ile Ala Met Glu
180 185 190
Leu Ile Arg Met Ile Lys Arg Gly Ile Asn Asp Arg Asn Phe Trp Arg
195 200 205
Gly Glu Asn Gly Arg Arg Thr Arg Thr Ala Tyr Glu Arg Met Cys Asn
210 215 220
Ile Leu Lys Gly Lys Phe Gln Thr Ala Ala Gln Arg Ala Met Met Asp
225 230 235 240
Gln Val Arg Glu Ser Arg Asn Pro Gly Asn Ala Glu Ile Glu Asp Leu
245 250 255
Ile Phe Leu Ala Arg Ser Ala Leu Ile Leu Arg Gly Ser Val Ala His
260 265 270
Lys Ser Cys Leu Pro Ala Cys Val Tyr Gly Leu Ala Val Ala Ser Gly
275 280 285
His Asp Phe Glu Arg Glu Gly Tyr Ser Leu Val Gly Ile Asp Pro Phe
290 295 300
Lys Leu Leu Gln Asn Ser Gln Val Phe Ser Leu Ile Arg Pro Asn Glu
305 310 315 320
Asn Pro Ala His Lys Ser Gln Leu Val Trp Met Ala Cys His Ser Ala
325 330 335
Ala Phe Glu Asp Leu Arg Val Ser Ser Phe Ile Arg Gly Lys Lys Val
340 345 350
Ile Pro Arg Gly Lys Leu Ser Thr Arg Gly Val Gln Ile Ala Ser Asn
355 360 365
Glu Asn Val Glu Ala Met Asp Ser Asn Thr Leu Glu Leu Arg Ser Arg
370 375 380
Tyr Trp Ala Ile Arg Thr Arg Ser Gly Gly Asn Thr Asn Gln Gln Lys
385 390 395 400
Ala Ser Ala Gly Gln Ile Ser Val Gln Pro Thr Phe Ser Val Gln Arg
405 410 415
Asn Leu Pro Phe Glu Arg Ala Thr Val Leu Ala Ala Phe Ser Gly Asn
420 425 430
Asn Glu Gly Arg Thr Ser Asp Met Arg Thr Glu Val Ile Arg Met Met
435 440 445
Glu Ser Ala Lys Pro Glu Asp Leu Ser Phe Gln Gly Arg Gly Val Phe
450 455 460
Glu Leu Ser Asp Glu Lys Ala Thr Ser Pro Ile Val Pro Ser Phe Asp
465 470 475 480
Met Ser Asn Glu Gly Ser Tyr Phe Phe Gly Asp Asn Ala Glu Glu Tyr
485 490 495
Asp Ser
<210> 50
<211> 1695
<212> DNA
<213> 猪流感病毒
<400> 50
atgaaggcaa tactagtagt cttgctatat acatttacaa ccgcaaaagc agacacatta 60
tgtataggtt accatgcaaa caattcaact gacactgtag acacagtact agaaaagaat 120
gtaacagtaa cacactctgt taaccttcta gaagacaggc ataacgggaa actatgtaaa 180
ctaagagggg tagccccatt gcatttgggt aaatgtaaca ttgctggatg gctcctggga 240
aatccagagt gtgaatcact cttcacagca agctcatggt cttacattgt ggaaacacct 300
aattcagaca atgggacgtg ttacccagga gatttcatca attatgaaga gctaagagag 360
cagttgagct cagtctcatc atttgaaaga tttgagatat tccccaagac aagttggccc 420
aatcatgaca cgaacagagg tgtgacggca gcatgtcctc atgctggagc aaatagcttc 480
tacagaaatt taatatggct ggttgaaaaa gaaaattcat acccaaagct cagcaaatcc 540
tatatcaaca ataaggagat ggaagtcctc gtgctatggg gcattcacca cccatctacc 600
agtgccgacc aacgaagtct ctaccagaat gcagatgcct atgtttttgt ggggtcatca 660
agatacagca agaagttcaa gccagaaata gcaataagac ccaaggtgag ggatcaagca 720
gggagaatga actattactg gacactagta gagcctggag ataaaataac attcgaagca 780
actggaaatc tagtggtacc gagatatgcc ttcgcaatga aaagaggttc aggatctggt 840
attatcattt cagatacatc agttcacgat tgtaacacga cttgtcagac acccaagggt 900
gctataaaca ccagcctccc atttcagaat gtacatccag tcacgattgg agaatgtcca 960
aaatatgtca aaagcacaaa attgagaatg gccacaggat taaggaatat cccgtctatt 1020
caatctagag gcctgtttgg tgccattgcc ggctttattg aggggggatg gacaggaatg 1080
atagatggat ggtacggtta tcaccatcaa aatgagcagg gatcaggata tgcagctgac 1140
ctaaagagca cacagaatgc cattgacggg atcactaaca aagtaaattc tgttattgaa 1200
aagatgaaca cacaattcac agcagtgggt aaagagttca accacctgga aaaaagaata 1260
gagaatttaa ataaaaaggt tgatgatggt tttctggatg tttggactta caatgctgag 1320
ctattggttc tgttggaaaa tgaaagaact ttggattacc acgattcaaa tgtgaagaac 1380
ttatatgaaa aagtaagaag ccagctaaaa aacaatgcca aggaaattgg aaatggctgc 1440
tttgaatttt accacaaatg tgatgacaca tgcatggaaa gcgtcaaaaa tgggacttat 1500
gattacccaa aatactcaga ggaagcaaaa ctaaacagag aggaaataga cggggtaaaa 1560
ctggaatcaa caaggattta ccagattttg gcgatctatt caactgtcgc cagttcattg 1620
gtactggtag tctccctggg ggcaatcagt ttctggatgt gctctaatgg gtctttacag 1680
tgcagaatat gtatt 1695
<210> 51
<211> 565
<212> PRT
<213> 猪流感病毒
<400> 51
Met Lys Ala Ile Leu Val Val Leu Leu Tyr Thr Phe Thr Thr Ala Lys
1 5 10 15
Ala Asp Thr Leu Cys Ile Gly Tyr His Ala Asn Asn Ser Thr Asp Thr
20 25 30
Val Asp Thr Val Leu Glu Lys Asn Val Thr Val Thr His Ser Val Asn
35 40 45
Leu Leu Glu Asp Arg His Asn Gly Lys Leu Cys Lys Leu Arg Gly Val
50 55 60
Ala Pro Leu His Leu Gly Lys Cys Asn Ile Ala Gly Trp Leu Leu Gly
65 70 75 80
Asn Pro Glu Cys Glu Ser Leu Phe Thr Ala Ser Ser Trp Ser Tyr Ile
85 90 95
Val Glu Thr Pro Asn Ser Asp Asn Gly Thr Cys Tyr Pro Gly Asp Phe
100 105 110
Ile Asn Tyr Glu Glu Leu Arg Glu Gln Leu Ser Ser Val Ser Ser Phe
115 120 125
Glu Arg Phe Glu Ile Phe Pro Lys Thr Ser Trp Pro Asn His Asp Thr
130 135 140
Asn Arg Gly Val Thr Ala Ala Cys Pro His Ala Gly Ala Asn Ser Phe
145 150 155 160
Tyr Arg Asn Leu Ile Trp Leu Val Glu Lys Glu Asn Ser Tyr Pro Lys
165 170 175
Leu Ser Lys Ser Tyr Ile Asn Asn Lys Glu Met Glu Val Leu Val Leu
180 185 190
Trp Gly Ile His His Pro Ser Thr Ser Ala Asp Gln Arg Ser Leu Tyr
195 200 205
Gln Asn Ala Asp Ala Tyr Val Phe Val Gly Ser Ser Arg Tyr Ser Lys
210 215 220
Lys Phe Lys Pro Glu Ile Ala Ile Arg Pro Lys Val Arg Asp Gln Ala
225 230 235 240
Gly Arg Met Asn Tyr Tyr Trp Thr Leu Val Glu Pro Gly Asp Lys Ile
245 250 255
Thr Phe Glu Ala Thr Gly Asn Leu Val Val Pro Arg Tyr Ala Phe Ala
260 265 270
Met Lys Arg Gly Ser Gly Ser Gly Ile Ile Ile Ser Asp Thr Ser Val
275 280 285
His Asp Cys Asn Thr Thr Cys Gln Thr Pro Lys Gly Ala Ile Asn Thr
290 295 300
Ser Leu Pro Phe Gln Asn Val His Pro Val Thr Ile Gly Glu Cys Pro
305 310 315 320
Lys Tyr Val Lys Ser Thr Lys Leu Arg Met Ala Thr Gly Leu Arg Asn
325 330 335
Ile Pro Ser Ile Gln Ser Arg Gly Leu Phe Gly Ala Ile Ala Gly Phe
340 345 350
Ile Glu Gly Gly Trp Thr Gly Met Ile Asp Gly Trp Tyr Gly Tyr His
355 360 365
His Gln Asn Glu Gln Gly Ser Gly Tyr Ala Ala Asp Leu Lys Ser Thr
370 375 380
Gln Asn Ala Ile Asp Gly Ile Thr Asn Lys Val Asn Ser Val Ile Glu
385 390 395 400
Lys Met Asn Thr Gln Phe Thr Ala Val Gly Lys Glu Phe Asn His Leu
405 410 415
Glu Lys Arg Ile Glu Asn Leu Asn Lys Lys Val Asp Asp Gly Phe Leu
420 425 430
Asp Val Trp Thr Tyr Asn Ala Glu Leu Leu Val Leu Leu Glu Asn Glu
435 440 445
Arg Thr Leu Asp Tyr His Asp Ser Asn Val Lys Asn Leu Tyr Glu Lys
450 455 460
Val Arg Ser Gln Leu Lys Asn Asn Ala Lys Glu Ile Gly Asn Gly Cys
465 470 475 480
Phe Glu Phe Tyr His Lys Cys Asp Asp Thr Cys Met Glu Ser Val Lys
485 490 495
Asn Gly Thr Tyr Asp Tyr Pro Lys Tyr Ser Glu Glu Ala Lys Leu Asn
500 505 510
Arg Glu Glu Ile Asp Gly Val Lys Leu Glu Ser Thr Arg Ile Tyr Gln
515 520 525
Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu Val Val
530 535 540
Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser Leu Gln
545 550 555 560
Cys Arg Ile Cys Ile
565
<210> 52
<211> 2148
<212> DNA
<213> 猪流感病毒
<400> 52
atggaagact ttgtgcgaca atgcttcaat ccaatgatcg tcgagcttgc ggaaaaggca 60
atgaaagaat atggagaaga tccgaaaatc gaaaccaaca aattcgctgc aatatgcaca 120
cacttggaag tctgtttcat gtattcagat ttccatttca tcgacgaacg gggtgaatca 180
ataattgtag aatctggtga tccaaatgca ttactgaagc accgatttga gataattgaa 240
ggaagagacc gaaccatggc ctggacagtg gtgaatagta tctgcaacac cacaggggta 300
gagaagccta aatttcttcc ggatttgtat gattacaaag agaaccgatt cattgaaatt 360
ggagtgacac ggagggaggt ccacatatac tacctagaga aagccaacaa aataaaatcc 420
gagaagacac acattcacat tttttcattc actggagagg agatggccac cagagcggac 480
tacacccttg atgaagagag cagggcaaga atcaaaacca ggcttttcac cataagacaa 540
gaaatggcca gtaggggtct atgggattcc tttcgtcaat ccgagagagg cgaagagaca 600
attgaagaaa gatttgaaat tacaggaacc atgcgcaggc ttgccgacca aagtctccca 660
ccgaacttct ccagccttga aaactttaga gcctatgtag atggattcga accgaacggc 720
tgcattgagg gcaagctttc tcaaatgtca aaagaagtga gcgccaaaat tgaaccattc 780
ttgaagacga caccacgccc cctcagattg cctggtgggc ctccttgctc tcagcggtca 840
aagttcctgc tgatggatgc tctgaaacta agtattgaag acccgagtca tgagggggaa 900
gggataccac tatatgatgc aatcaaatgc atgaagacat tttttggctg gaaagagcct 960
aacataatca aaccacatga gaaaggcata aaccccaatt acctcctggc ttggaagcag 1020
gtgctagcag agctgcagga cattgaaaat gaagagaaga tcccaaaaac aaagaacatg 1080
aagagaacga gccaattgaa gtgggcactc ggtgagaata tggcaccaga gaaagtagac 1140
tttgatgagt gcaaagatgt tggtgatctt aaacagtatg acagcgatga gccagagccc 1200
agatctctag caagctgggt ccaaaatgaa ttcaataagg catgtgaatt gaccgattca 1260
agctggatag aacttgatga gataggagaa gatgttgccc cgattgaaca catcgcaagc 1320
atgaggagga actattttac agcagaagtg tcccattgca gggctactga atacataatg 1380
aagggagtgt acataaatac ggctttgctc aatgcatctt gcgcagccat ggatgacttc 1440
cagctgatcc caatgataag caaatgtagg accaaagaag gaagacggaa aacaaatctg 1500
tatgggttca ttataaaagg aaggtctcat ttgagaaatg atactgacgt ggtgaacttt 1560
gtaagcatgg agttctccct cactgacccg aaactggagc cacacaaatg ggaaaagtac 1620
tgtgttcttg aaataggaga tatgctcctg aggactgcga taggccaagt gtcgaggccc 1680
atgttcctat atgtgagaac caatggaacc tctaagatca agatgaaatg gggcatggaa 1740
atgaggcgct gccttcttca gtctcttcag cagattgaga gcatgattga agcagagtct 1800
tctgtcaaag agaaagacat gaccaaggaa ttctttgaaa ccaaatcgga aacatggcca 1860
atcggagaat cacccaaagg agtggaggaa ggctctattg ggaaagtgtg caggacctta 1920
ctggcaaaat ctgtattcaa tagtctatac gcgtctccac aacttgaggg gttttcggct 1980
gaatcgagaa aattgcttct cattgtccag gcacttaggg acaacctgga acctggaacc 2040
ttcgatcttg gggggctata tgaagcaatc gaggagtgcc tgattaatga tccctgggtt 2100
ttgcttaatg catcttggtt caactccttc ctcacacatg cactgaaa 2148
<210> 53
<211> 716
<212> PRT
<213> 猪流感病毒
<400> 53
Met Glu Asp Phe Val Arg Gln Cys Phe Asn Pro Met Ile Val Glu Leu
1 5 10 15
Ala Glu Lys Ala Met Lys Glu Tyr Gly Glu Asp Pro Lys Ile Glu Thr
20 25 30
Asn Lys Phe Ala Ala Ile Cys Thr His Leu Glu Val Cys Phe Met Tyr
35 40 45
Ser Asp Phe His Phe Ile Asp Glu Arg Gly Glu Ser Ile Ile Val Glu
50 55 60
Ser Gly Asp Pro Asn Ala Leu Leu Lys His Arg Phe Glu Ile Ile Glu
65 70 75 80
Gly Arg Asp Arg Thr Met Ala Trp Thr Val Val Asn Ser Ile Cys Asn
85 90 95
Thr Thr Gly Val Glu Lys Pro Lys Phe Leu Pro Asp Leu Tyr Asp Tyr
100 105 110
Lys Glu Asn Arg Phe Ile Glu Ile Gly Val Thr Arg Arg Glu Val His
115 120 125
Ile Tyr Tyr Leu Glu Lys Ala Asn Lys Ile Lys Ser Glu Lys Thr His
130 135 140
Ile His Ile Phe Ser Phe Thr Gly Glu Glu Met Ala Thr Arg Ala Asp
145 150 155 160
Tyr Thr Leu Asp Glu Glu Ser Arg Ala Arg Ile Lys Thr Arg Leu Phe
165 170 175
Thr Ile Arg Gln Glu Met Ala Ser Arg Gly Leu Trp Asp Ser Phe Arg
180 185 190
Gln Ser Glu Arg Gly Glu Glu Thr Ile Glu Glu Arg Phe Glu Ile Thr
195 200 205
Gly Thr Met Arg Arg Leu Ala Asp Gln Ser Leu Pro Pro Asn Phe Ser
210 215 220
Ser Leu Glu Asn Phe Arg Ala Tyr Val Asp Gly Phe Glu Pro Asn Gly
225 230 235 240
Cys Ile Glu Gly Lys Leu Ser Gln Met Ser Lys Glu Val Ser Ala Lys
245 250 255
Ile Glu Pro Phe Leu Lys Thr Thr Pro Arg Pro Leu Arg Leu Pro Gly
260 265 270
Gly Pro Pro Cys Ser Gln Arg Ser Lys Phe Leu Leu Met Asp Ala Leu
275 280 285
Lys Leu Ser Ile Glu Asp Pro Ser His Glu Gly Glu Gly Ile Pro Leu
290 295 300
Tyr Asp Ala Ile Lys Cys Met Lys Thr Phe Phe Gly Trp Lys Glu Pro
305 310 315 320
Asn Ile Ile Lys Pro His Glu Lys Gly Ile Asn Pro Asn Tyr Leu Leu
325 330 335
Ala Trp Lys Gln Val Leu Ala Glu Leu Gln Asp Ile Glu Asn Glu Glu
340 345 350
Lys Ile Pro Lys Thr Lys Asn Met Lys Arg Thr Ser Gln Leu Lys Trp
355 360 365
Ala Leu Gly Glu Asn Met Ala Pro Glu Lys Val Asp Phe Asp Glu Cys
370 375 380
Lys Asp Val Gly Asp Leu Lys Gln Tyr Asp Ser Asp Glu Pro Glu Pro
385 390 395 400
Arg Ser Leu Ala Ser Trp Val Gln Asn Glu Phe Asn Lys Ala Cys Glu
405 410 415
Leu Thr Asp Ser Ser Trp Ile Glu Leu Asp Glu Ile Gly Glu Asp Val
420 425 430
Ala Pro Ile Glu His Ile Ala Ser Met Arg Arg Asn Tyr Phe Thr Ala
435 440 445
Glu Val Ser His Cys Arg Ala Thr Glu Tyr Ile Met Lys Gly Val Tyr
450 455 460
Ile Asn Thr Ala Leu Leu Asn Ala Ser Cys Ala Ala Met Asp Asp Phe
465 470 475 480
Gln Leu Ile Pro Met Ile Ser Lys Cys Arg Thr Lys Glu Gly Arg Arg
485 490 495
Lys Thr Asn Leu Tyr Gly Phe Ile Ile Lys Gly Arg Ser His Leu Arg
500 505 510
Asn Asp Thr Asp Val Val Asn Phe Val Ser Met Glu Phe Ser Leu Thr
515 520 525
Asp Pro Lys Leu Glu Pro His Lys Trp Glu Lys Tyr Cys Val Leu Glu
530 535 540
Ile Gly Asp Met Leu Leu Arg Thr Ala Ile Gly Gln Val Ser Arg Pro
545 550 555 560
Met Phe Leu Tyr Val Arg Thr Asn Gly Thr Ser Lys Ile Lys Met Lys
565 570 575
Trp Gly Met Glu Met Arg Arg Cys Leu Leu Gln Ser Leu Gln Gln Ile
580 585 590
Glu Ser Met Ile Glu Ala Glu Ser Ser Val Lys Glu Lys Asp Met Thr
595 600 605
Lys Glu Phe Phe Glu Thr Lys Ser Glu Thr Trp Pro Ile Gly Glu Ser
610 615 620
Pro Lys Gly Val Glu Glu Gly Ser Ile Gly Lys Val Cys Arg Thr Leu
625 630 635 640
Leu Ala Lys Ser Val Phe Asn Ser Leu Tyr Ala Ser Pro Gln Leu Glu
645 650 655
Gly Phe Ser Ala Glu Ser Arg Lys Leu Leu Leu Ile Val Gln Ala Leu
660 665 670
Arg Asp Asn Leu Glu Pro Gly Thr Phe Asp Leu Gly Gly Leu Tyr Glu
675 680 685
Ala Ile Glu Glu Cys Leu Ile Asn Asp Pro Trp Val Leu Leu Asn Ala
690 695 700
Ser Trp Phe Asn Ser Phe Leu Thr His Ala Leu Lys
705 710 715
<210> 54
<211> 2271
<212> DNA
<213> 猪流感病毒
<400> 54
atggatgtca atccgactct acttttccta agggttccag cgcaaaatgc cataagcacc 60
acattccctt atactggaga tcctccatac agccatggaa caggaacagg atacaccatg 120
gacacagtca acagaacaca ccaatattca gagaaaggga agtggacgac aaacacagag 180
acaggggcac cccagctcaa cccgattgat ggaccactac ctgaggataa tgaaccaagt 240
ggatatgcac aaacagactg tgttctggag gccatggctt tccttgaaga atcccaccca 300
gggatatttg agaattcatg ccttgagaca atggaagttg ttcaacaaac aagggtggat 360
aaactaactc aaggtcgcca gacttatgat tggacattaa acagaaatca accggcagca 420
actgcattgg caaacaccat agaagttttt agatcaaatg gtctaacagc taatgagtca 480
ggaaggctaa tagatttcct aaaggatgta atggaatcaa tggataaaga ggaaatagag 540
ataacaacac actttcaaag aaaaaggaga gtaagagaca acatgaccaa gaagatggtc 600
acacaaagaa caataggaaa gaaaaaacaa agaatgaata agagaggtta tctaataaga 660
gcactaacat tgaatacgat gaccaaagat gcagagagag gcaaattaaa aagaagggct 720
atcgcaacac ctgggatgca aattagaggg ttcgtgtact ttgttgaaac tttagctaga 780
agcatttgcg aaaagctgga acagtctgga ctcccagtag ggggcaatga aaagaaggcc 840
aaattggcaa atgttgtgag aaagatgatg actaattcac aagacacaga gctttctttc 900
acaatcactg gggacaacac taagtggaat gaaaatcaaa atcctcgaat gttcctggcg 960
atgattacat atatcaccag aaatcaaccc gaatggttca gaaacatcct gagcatggca 1020
cccataatgt tctcaaacaa aatggcaagg ctaggaaaag ggtacatgtt cgagagtaaa 1080
agaatgaagc tccgaacaca aataccatca gaaatgctag caagcattga cctgaagtat 1140
ttcaatgaat caacaaggaa gaaaattgag aaaataaggc ctcttctaat agatggcaca 1200
gcatcattga gccctggaat gatgatgggc atgttcaaca tgctaagtac ggttttggga 1260
gtctcaatac tgaatcttgg acaaaagaaa tacaccaaga caacgtactg gtgggatggg 1320
cttcaatcct ccgacgattt tgtcctcata gtgaatgcat caaatcatga gggaatacaa 1380
gcaggagtgg atagattcta caggacctgc aagttagtgg gaatcaacat gagcaaaaag 1440
aagtcctata taaataagac agggacattt gaattcacaa gcttttttta tcgctatgga 1500
tttgtggcta attttagcat ggagctgccc agttttggag tgtctggaat aaatgaatca 1560
gctgatatga gtattggagt aacaatgata aagaacaaca tgataaacaa tgaccttgga 1620
cctgcaacag cccagatggc ccttcaattg ttcatcaaag actacagata cacatatagg 1680
tgccatagag gagacacaca aattcagacg agaagatcat tcgagctaaa gaagctgtgg 1740
gatcaaaccc aatcaaaggc aggactatta gtatctgatg gaggaccaaa cttatacaat 1800
atccggaatc ttcacattcc tgaagtctgc ttaaaatggg agctaatgga tgagggttat 1860
cggggaagac tttgtaatcc cctgaatcct tttgtcagcc ataaagagat tgattctgta 1920
aacaatgctg tggtgatgcc agcccatggt ccagccaaaa gcatggaata tgatgccgtt 1980
gcaactacac actcctggat tcccaagagg aaccgctcta ttctcaacac aagccaaagg 2040
ggaattcttg aggatgaaca gatgtaccag aagtgctgca acctgttcga gaaatttttc 2100
cctagtagtt catacaggag accggttgga atttctagca tggtggaggc catggtgtct 2160
agagcccgga ttgatgccag aattgacttc gagtctggac ggattaagaa agaagagttc 2220
tctgagatca tgaagatctg ttccaccatt gaagaactca gacggcaaaa a 2271
<210> 55
<211> 757
<212> PRT
<213> 猪流感病毒
<400> 55
Met Asp Val Asn Pro Thr Leu Leu Phe Leu Arg Val Pro Ala Gln Asn
1 5 10 15
Ala Ile Ser Thr Thr Phe Pro Tyr Thr Gly Asp Pro Pro Tyr Ser His
20 25 30
Gly Thr Gly Thr Gly Tyr Thr Met Asp Thr Val Asn Arg Thr His Gln
35 40 45
Tyr Ser Glu Lys Gly Lys Trp Thr Thr Asn Thr Glu Thr Gly Ala Pro
50 55 60
Gln Leu Asn Pro Ile Asp Gly Pro Leu Pro Glu Asp Asn Glu Pro Ser
65 70 75 80
Gly Tyr Ala Gln Thr Asp Cys Val Leu Glu Ala Met Ala Phe Leu Glu
85 90 95
Glu Ser His Pro Gly Ile Phe Glu Asn Ser Cys Leu Glu Thr Met Glu
100 105 110
Val Val Gln Gln Thr Arg Val Asp Lys Leu Thr Gln Gly Arg Gln Thr
115 120 125
Tyr Asp Trp Thr Leu Asn Arg Asn Gln Pro Ala Ala Thr Ala Leu Ala
130 135 140
Asn Thr Ile Glu Val Phe Arg Ser Asn Gly Leu Thr Ala Asn Glu Ser
145 150 155 160
Gly Arg Leu Ile Asp Phe Leu Lys Asp Val Met Glu Ser Met Asp Lys
165 170 175
Glu Glu Ile Glu Ile Thr Thr His Phe Gln Arg Lys Arg Arg Val Arg
180 185 190
Asp Asn Met Thr Lys Lys Met Val Thr Gln Arg Thr Ile Gly Lys Lys
195 200 205
Lys Gln Arg Met Asn Lys Arg Gly Tyr Leu Ile Arg Ala Leu Thr Leu
210 215 220
Asn Thr Met Thr Lys Asp Ala Glu Arg Gly Lys Leu Lys Arg Arg Ala
225 230 235 240
Ile Ala Thr Pro Gly Met Gln Ile Arg Gly Phe Val Tyr Phe Val Glu
245 250 255
Thr Leu Ala Arg Ser Ile Cys Glu Lys Leu Glu Gln Ser Gly Leu Pro
260 265 270
Val Gly Gly Asn Glu Lys Lys Ala Lys Leu Ala Asn Val Val Arg Lys
275 280 285
Met Met Thr Asn Ser Gln Asp Thr Glu Leu Ser Phe Thr Ile Thr Gly
290 295 300
Asp Asn Thr Lys Trp Asn Glu Asn Gln Asn Pro Arg Met Phe Leu Ala
305 310 315 320
Met Ile Thr Tyr Ile Thr Arg Asn Gln Pro Glu Trp Phe Arg Asn Ile
325 330 335
Leu Ser Met Ala Pro Ile Met Phe Ser Asn Lys Met Ala Arg Leu Gly
340 345 350
Lys Gly Tyr Met Phe Glu Ser Lys Arg Met Lys Leu Arg Thr Gln Ile
355 360 365
Pro Ser Glu Met Leu Ala Ser Ile Asp Leu Lys Tyr Phe Asn Glu Ser
370 375 380
Thr Arg Lys Lys Ile Glu Lys Ile Arg Pro Leu Leu Ile Asp Gly Thr
385 390 395 400
Ala Ser Leu Ser Pro Gly Met Met Met Gly Met Phe Asn Met Leu Ser
405 410 415
Thr Val Leu Gly Val Ser Ile Leu Asn Leu Gly Gln Lys Lys Tyr Thr
420 425 430
Lys Thr Thr Tyr Trp Trp Asp Gly Leu Gln Ser Ser Asp Asp Phe Val
435 440 445
Leu Ile Val Asn Ala Ser Asn His Glu Gly Ile Gln Ala Gly Val Asp
450 455 460
Arg Phe Tyr Arg Thr Cys Lys Leu Val Gly Ile Asn Met Ser Lys Lys
465 470 475 480
Lys Ser Tyr Ile Asn Lys Thr Gly Thr Phe Glu Phe Thr Ser Phe Phe
485 490 495
Tyr Arg Tyr Gly Phe Val Ala Asn Phe Ser Met Glu Leu Pro Ser Phe
500 505 510
Gly Val Ser Gly Ile Asn Glu Ser Ala Asp Met Ser Ile Gly Val Thr
515 520 525
Met Ile Lys Asn Asn Met Ile Asn Asn Asp Leu Gly Pro Ala Thr Ala
530 535 540
Gln Met Ala Leu Gln Leu Phe Ile Lys Asp Tyr Arg Tyr Thr Tyr Arg
545 550 555 560
Cys His Arg Gly Asp Thr Gln Ile Gln Thr Arg Arg Ser Phe Glu Leu
565 570 575
Lys Lys Leu Trp Asp Gln Thr Gln Ser Lys Ala Gly Leu Leu Val Ser
580 585 590
Asp Gly Gly Pro Asn Leu Tyr Asn Ile Arg Asn Leu His Ile Pro Glu
595 600 605
Val Cys Leu Lys Trp Glu Leu Met Asp Glu Gly Tyr Arg Gly Arg Leu
610 615 620
Cys Asn Pro Leu Asn Pro Phe Val Ser His Lys Glu Ile Asp Ser Val
625 630 635 640
Asn Asn Ala Val Val Met Pro Ala His Gly Pro Ala Lys Ser Met Glu
645 650 655
Tyr Asp Ala Val Ala Thr Thr His Ser Trp Ile Pro Lys Arg Asn Arg
660 665 670
Ser Ile Leu Asn Thr Ser Gln Arg Gly Ile Leu Glu Asp Glu Gln Met
675 680 685
Tyr Gln Lys Cys Cys Asn Leu Phe Glu Lys Phe Phe Pro Ser Ser Ser
690 695 700
Tyr Arg Arg Pro Val Gly Ile Ser Ser Met Val Glu Ala Met Val Ser
705 710 715 720
Arg Ala Arg Ile Asp Ala Arg Ile Asp Phe Glu Ser Gly Arg Ile Lys
725 730 735
Lys Glu Glu Phe Ser Glu Ile Met Lys Ile Cys Ser Thr Ile Glu Glu
740 745 750
Leu Arg Arg Gln Lys
755
<210> 56
<211> 2277
<212> DNA
<213> 猪流感病毒
<400> 56
atggagagaa taaaggaact aagagatcta atgtcgcagt cccgcactcg cgagatactc 60
actaagacca ctgtggacca tatggccata atcaaaaagt acacatcagg aaggcaagag 120
aagaatcccg cactcagaat gaagtggatg atggcaatga aatacccaat tacagcagac 180
aagagaataa tgggcatgat tccagagagg aatgaacaag gacaaaccct ctggagcaaa 240
acaaacgatg ctggatcaga acgcgtgatg gtatcacctc tggccgtaac atggtggaat 300
agaaatggcc caacaacaag tacagttcac taccctaagg tatataaaac ttatttcgaa 360
aaagtcgaaa ggttaaaaca tggtaccttt ggccctgtcc acttcagaaa tcaagttaaa 420
ataagaagga gagttgacac aaaccctggt cacgcagatc tcagtgccaa ggaggcacag 480
gatgtgatca tggaagttgt tttcccaaat gaagtggggg caagaatact gacatcagag 540
tcacagctga caataacaaa ggagaagaaa gaagagctcc aggattgtaa aattgctccc 600
ttgatggtgg catacatgct agaaagagag ttggtccgta aaacgaggtt tctcccggtg 660
gctggtggaa caggcagtgt ttatattgag gtgctgcact taacccaggg aacatgctgg 720
gagcagatgt acactccagg aggagaagtg agaaatgatg atgttgacca aagtttgatt 780
atcgctgcta gaaacatagt aagaagagca gcagtgtcag cagacccatt agcatctctc 840
ttggaaatgt gccacagcac acagattgga ggaataagga tggtagacat ccttagacag 900
aatccaacag aggaacaagc cgtagacata tgcaaggcag caatggggtt gaggattagc 960
tcatctttca gctttggtgg gttcactttc aaaagaacaa gcggatcatc agtcaagaaa 1020
gaagaagaaa tgctcacagg caacctccaa acactgaaaa taagagtaca tgaaggatat 1080
gaagaattca caatggtagg gagaagagca acagctattc tcagaaaggc aaccaggaga 1140
ttgatccagt taatagtaag tgggagagac gagcagtcaa ttgctgaggc aataattgtg 1200
gccatggtat tttcacaaga agattgcatg atcaaggcag ttaggggcga tctgaacttt 1260
gtcaataggg caaaccagcg actgaatccc atgcaccaac tcttgagaca tttccaaaaa 1320
gatgcgaaag tgcttttcca gaactgggga attgaaccta tcgacaatgt gatgggaatg 1380
attggaatat tgcccgatat gaccccaagc acggagatgt cgctgagagg gataagagtc 1440
agcaaaatgg gagtagatga atactccagc acggagagag tggtagtgag cattgaccga 1500
tttttgaggg ttcgggatca acgagggaac gtactattgt ctcccgaaga ggtcagcgag 1560
acacaaggaa cggagaagtt gacaataact tattcgtcat caatgatgtg ggagatcaat 1620
ggtcctgagt cagtgctggt caacacttat caatggatca tcaggaactg ggaaactgtg 1680
aaaattcaat ggtcacaaga ccccacgatg ttatacaaca aaatggaatt tgaaccattt 1740
cagtctcttg tccctaaggc aaccagaagc cgatacagtg gattcgtaag gacactgttc 1800
cagcaaatgc gggatgtgct tggaacattt gacactgtcc aaataataaa acttctccca 1860
tttgctgctg ctccaccaga acagagtagg atgcagtttt cctcattgac tgtgaatgtg 1920
agaggatcag ggttgaggat actggtgaga ggcaattctc cagtattcaa ttacaacaag 1980
gcaaccaaaa ggcttacagt tcttgggaaa gatgcaggtg cattgactga agatccagat 2040
gaaggcacag ctggggtgga gtctgctgtc ctgagaggat ttctcatttt gggcaaagaa 2100
gacaagagat atggaccagc attaagcatc aatgaactga gcaatcttgc aagaggagag 2160
aaggctaatg tgctaattgg gcaaggagac gtagtgttgg taatgaaacg gaaacgagac 2220
tctagcatac ttactgacag ccagacagcg accaaaagaa ttcggatggc catcaat 2277
<210> 57
<211> 759
<212> PRT
<213> 猪流感病毒
<400> 57
Met Glu Arg Ile Lys Glu Leu Arg Asp Leu Met Ser Gln Ser Arg Thr
1 5 10 15
Arg Glu Ile Leu Thr Lys Thr Thr Val Asp His Met Ala Ile Ile Lys
20 25 30
Lys Tyr Thr Ser Gly Arg Gln Glu Lys Asn Pro Ala Leu Arg Met Lys
35 40 45
Trp Met Met Ala Met Lys Tyr Pro Ile Thr Ala Asp Lys Arg Ile Met
50 55 60
Gly Met Ile Pro Glu Arg Asn Glu Gln Gly Gln Thr Leu Trp Ser Lys
65 70 75 80
Thr Asn Asp Ala Gly Ser Glu Arg Val Met Val Ser Pro Leu Ala Val
85 90 95
Thr Trp Trp Asn Arg Asn Gly Pro Thr Thr Ser Thr Val His Tyr Pro
100 105 110
Lys Val Tyr Lys Thr Tyr Phe Glu Lys Val Glu Arg Leu Lys His Gly
115 120 125
Thr Phe Gly Pro Val His Phe Arg Asn Gln Val Lys Ile Arg Arg Arg
130 135 140
Val Asp Thr Asn Pro Gly His Ala Asp Leu Ser Ala Lys Glu Ala Gln
145 150 155 160
Asp Val Ile Met Glu Val Val Phe Pro Asn Glu Val Gly Ala Arg Ile
165 170 175
Leu Thr Ser Glu Ser Gln Leu Thr Ile Thr Lys Glu Lys Lys Glu Glu
180 185 190
Leu Gln Asp Cys Lys Ile Ala Pro Leu Met Val Ala Tyr Met Leu Glu
195 200 205
Arg Glu Leu Val Arg Lys Thr Arg Phe Leu Pro Val Ala Gly Gly Thr
210 215 220
Gly Ser Val Tyr Ile Glu Val Leu His Leu Thr Gln Gly Thr Cys Trp
225 230 235 240
Glu Gln Met Tyr Thr Pro Gly Gly Glu Val Arg Asn Asp Asp Val Asp
245 250 255
Gln Ser Leu Ile Ile Ala Ala Arg Asn Ile Val Arg Arg Ala Ala Val
260 265 270
Ser Ala Asp Pro Leu Ala Ser Leu Leu Glu Met Cys His Ser Thr Gln
275 280 285
Ile Gly Gly Ile Arg Met Val Asp Ile Leu Arg Gln Asn Pro Thr Glu
290 295 300
Glu Gln Ala Val Asp Ile Cys Lys Ala Ala Met Gly Leu Arg Ile Ser
305 310 315 320
Ser Ser Phe Ser Phe Gly Gly Phe Thr Phe Lys Arg Thr Ser Gly Ser
325 330 335
Ser Val Lys Lys Glu Glu Glu Met Leu Thr Gly Asn Leu Gln Thr Leu
340 345 350
Lys Ile Arg Val His Glu Gly Tyr Glu Glu Phe Thr Met Val Gly Arg
355 360 365
Arg Ala Thr Ala Ile Leu Arg Lys Ala Thr Arg Arg Leu Ile Gln Leu
370 375 380
Ile Val Ser Gly Arg Asp Glu Gln Ser Ile Ala Glu Ala Ile Ile Val
385 390 395 400
Ala Met Val Phe Ser Gln Glu Asp Cys Met Ile Lys Ala Val Arg Gly
405 410 415
Asp Leu Asn Phe Val Asn Arg Ala Asn Gln Arg Leu Asn Pro Met His
420 425 430
Gln Leu Leu Arg His Phe Gln Lys Asp Ala Lys Val Leu Phe Gln Asn
435 440 445
Trp Gly Ile Glu Pro Ile Asp Asn Val Met Gly Met Ile Gly Ile Leu
450 455 460
Pro Asp Met Thr Pro Ser Thr Glu Met Ser Leu Arg Gly Ile Arg Val
465 470 475 480
Ser Lys Met Gly Val Asp Glu Tyr Ser Ser Thr Glu Arg Val Val Val
485 490 495
Ser Ile Asp Arg Phe Leu Arg Val Arg Asp Gln Arg Gly Asn Val Leu
500 505 510
Leu Ser Pro Glu Glu Val Ser Glu Thr Gln Gly Thr Glu Lys Leu Thr
515 520 525
Ile Thr Tyr Ser Ser Ser Met Met Trp Glu Ile Asn Gly Pro Glu Ser
530 535 540
Val Leu Val Asn Thr Tyr Gln Trp Ile Ile Arg Asn Trp Glu Thr Val
545 550 555 560
Lys Ile Gln Trp Ser Gln Asp Pro Thr Met Leu Tyr Asn Lys Met Glu
565 570 575
Phe Glu Pro Phe Gln Ser Leu Val Pro Lys Ala Thr Arg Ser Arg Tyr
580 585 590
Ser Gly Phe Val Arg Thr Leu Phe Gln Gln Met Arg Asp Val Leu Gly
595 600 605
Thr Phe Asp Thr Val Gln Ile Ile Lys Leu Leu Pro Phe Ala Ala Ala
610 615 620
Pro Pro Glu Gln Ser Arg Met Gln Phe Ser Ser Leu Thr Val Asn Val
625 630 635 640
Arg Gly Ser Gly Leu Arg Ile Leu Val Arg Gly Asn Ser Pro Val Phe
645 650 655
Asn Tyr Asn Lys Ala Thr Lys Arg Leu Thr Val Leu Gly Lys Asp Ala
660 665 670
Gly Ala Leu Thr Glu Asp Pro Asp Glu Gly Thr Ala Gly Val Glu Ser
675 680 685
Ala Val Leu Arg Gly Phe Leu Ile Leu Gly Lys Glu Asp Lys Arg Tyr
690 695 700
Gly Pro Ala Leu Ser Ile Asn Glu Leu Ser Asn Leu Ala Arg Gly Glu
705 710 715 720
Lys Ala Asn Val Leu Ile Gly Gln Gly Asp Val Val Leu Val Met Lys
725 730 735
Arg Lys Arg Asp Ser Ser Ile Leu Thr Asp Ser Gln Thr Ala Thr Lys
740 745 750
Arg Ile Arg Met Ala Ile Asn
755
<210> 58
<211> 372
<212> DNA
<213> 猪流感病毒
<400> 58
atggactcca atactgtgtc aagctttcag ctcttccagg acatactaat gaggatgtca 60
aaaatgcagt tggggtcctc atcggaggac ttgaatggaa tggtaacacg gttcgaggct 120
ctgaaaatct acagagattc gcttggagaa accgtaatga gaatgggaga ccttcattac 180
ctccagaaca gaaatgaaaa gtggcgagag caattgggac agaaatttga ggaaataaga 240
tggttaattg aagaagtacg gcacagattg aaagcgacag aaaatagttt cgaacaaata 300
acatttatgc aagccttaca actactgctt gaagtagaac aagagataag gactttctcg 360
tttcagctta tt 372
<210> 59
<211> 121
<212> PRT
<213> 猪流感病毒
<400> 59
Met Asp Ser Asn Thr Val Ser Ser Phe Gln Asp Ile Leu Met Arg Met
1 5 10 15
Ser Lys Met Gln Leu Gly Ser Ser Ser Glu Asp Leu Asn Gly Met Val
20 25 30
Thr Arg Phe Glu Ala Leu Lys Ile Tyr Arg Asp Ser Leu Gly Glu Thr
35 40 45
Val Met Arg Met Gly Asp Leu His Tyr Leu Gln Asn Arg Asn Glu Lys
50 55 60
Trp Arg Glu Gln Leu Gly Gln Lys Phe Glu Glu Ile Arg Trp Leu Ile
65 70 75 80
Glu Glu Val Arg His Arg Leu Lys Ala Thr Glu Asn Ser Phe Glu Gln
85 90 95
Ile Thr Phe Met Gln Ala Leu Gln Leu Leu Leu Glu Val Glu Gln Glu
100 105 110
Ile Arg Thr Phe Ser Phe Gln Leu Ile
115 120
<210> 60
<211> 657
<212> DNA
<213> 猪流感病毒
<400> 60
atggactcca atactgtgtc aagctttcag gtagactgtt tcctttggca catccgcaaa 60
cggtttgcag acaatggatt gggtgatgcc ccgttccttg atcggctccg ccgagatcaa 120
aagtccctga aaggaagagg caacaccctt agcctagaca tcgaaacagc cactcttgtt 180
gggaaacaaa ttgttgagtg gattttgaaa gaggaatcca gcgatacact taagatgacc 240
attgcatctg tacctacttc gcgctaccta gctgacatga ccctcgagga aatgtcacga 300
gactggttca tgctcatgcc taggcaaaag ataataggcc ctctttgtgt gcgaatggac 360
caggcgatca tggaaaagaa catcatactg aaagcgaact tcagtgtgat ctttaaccga 420
ttagagactt tgatactact aagggctttc actgaggagg gagcaatcgt tggagaaatt 480
tcaccattac cttctcttcc aggacatact aatgaggatg tcaaaaatgc agttggggtc 540
ctcatcggag gacttgaatg gaatggtaac acggttcgag gctctgaaaa tctacagaga 600
ttcgcttgga gaaaccgtaa tgagaatggg agaccttcat tacctccaga acagaaa 657
<210> 61
<211> 219
<212> PRT
<213> 猪流感病毒
<400> 61
Met Asp Ser Asn Thr Val Ser Ser Phe Gln Val Asp Cys Phe Leu Trp
1 5 10 15
His Ile Arg Lys Arg Phe Ala Asp Asn Gly Leu Gly Asp Ala Pro Phe
20 25 30
Leu Asp Arg Leu Arg Arg Asp Gln Lys Ser Leu Lys Gly Arg Gly Asn
35 40 45
Thr Leu Ser Leu Asp Ile Glu Thr Ala Thr Leu Val Gly Lys Gln Ile
50 55 60
Val Glu Trp Ile Leu Lys Glu Glu Ser Ser Asp Thr Leu Lys Met Thr
65 70 75 80
Ile Ala Ser Val Pro Thr Ser Arg Tyr Leu Ala Asp Met Thr Leu Glu
85 90 95
Glu Met Ser Arg Asp Trp Phe Met Leu Met Pro Arg Gln Lys Ile Ile
100 105 110
Gly Pro Leu Cys Val Arg Met Asp Gln Ala Ile Met Glu Lys Asn Ile
115 120 125
Ile Leu Lys Ala Asn Phe Ser Val Ile Phe Asn Arg Leu Glu Thr Leu
130 135 140
Ile Leu Leu Arg Ala Phe Thr Glu Glu Gly Ala Ile Val Gly Glu Ile
145 150 155 160
Ser Pro Leu Pro Ser Leu Pro Gly His Thr Asn Glu Asp Val Lys Asn
165 170 175
Ala Val Gly Val Leu Ile Gly Gly Leu Glu Trp Asn Gly Asn Thr Val
180 185 190
Arg Gly Ser Glu Asn Leu Gln Arg Phe Ala Trp Arg Asn Arg Asn Glu
195 200 205
Asn Gly Arg Pro Ser Leu Pro Pro Glu Gln Lys
210 215
<210> 62
<211> 756
<212> DNA
<213> 猪流感病毒
<400> 62
atgagtcttc taaccgaggt cgaaacgtat gttctctcta tcgtcccgtc aggccccctc 60
aaagccgaga tagcacagag actcgaagac gtttttgcag ggaaaaacac cgatcttgag 120
gctctcatgg aatggctaaa gacaagacca atcctgtcac ctctgactaa ggggatttta 180
gggtttgtgt tcacgctcac cgtgcccagt gagcgaggac tgcagcgtag acgttttgtc 240
cagaatgccc tcaatgggaa tggtgacccg aacaacatgg acaaggcggt caaactgtac 300
aggaaactaa aaagggaaat aacattccat ggggccaagg aagtagcgct cagttactct 360
gctggtgcac ttgccagttg catgggcctc atatacaaca gaatggggac tgtcgccact 420
gaggtggcat ttggtctggt atgcgcaacc tgtgaacaga ttgctgattc tcagcatcga 480
tctcatagac aaatggtgac aacaaccaat ccactaatca ggcacgagaa cagaatggta 540
atagccagca caacagctaa ggccatggaa caaatggctg gatcaagtga acaagcagca 600
gaggctatgg aggttgccag ccaggctaga caaatggtac aggcaatgag aacaattggg 660
actcacccta gttccagcac tggtctaaaa gatgatcttc ttgaaaattt acaggcctat 720
cagaaacgga tgggagtgca aatgcaacga ttcaag 756
<210> 63
<211> 252
<212> PRT
<213> 猪流感病毒
<400> 63
Met Ser Leu Leu Thr Glu Val Glu Thr Tyr Val Leu Ser Ile Val Pro
1 5 10 15
Ser Gly Pro Leu Lys Ala Glu Ile Ala Gln Arg Leu Glu Asp Val Phe
20 25 30
Ala Gly Lys Asn Thr Asp Leu Glu Ala Leu Met Glu Trp Leu Lys Thr
35 40 45
Arg Pro Ile Leu Ser Pro Leu Thr Lys Gly Ile Leu Gly Phe Val Phe
50 55 60
Thr Leu Thr Val Pro Ser Glu Arg Gly Leu Gln Arg Arg Arg Phe Val
65 70 75 80
Gln Asn Ala Leu Asn Gly Asn Gly Asp Pro Asn Asn Met Asp Lys Ala
85 90 95
Val Lys Leu Tyr Arg Lys Leu Lys Arg Glu Ile Thr Phe His Gly Ala
100 105 110
Lys Glu Val Ala Leu Ser Tyr Ser Ala Gly Ala Leu Ala Ser Cys Met
115 120 125
Gly Leu Ile Tyr Asn Arg Met Gly Thr Val Ala Thr Glu Val Ala Phe
130 135 140
Gly Leu Val Cys Ala Thr Cys Glu Gln Ile Ala Asp Ser Gln His Arg
145 150 155 160
Ser His Arg Gln Met Val Thr Thr Thr Asn Pro Leu Ile Arg His Glu
165 170 175
Asn Arg Met Val Ile Ala Ser Thr Thr Ala Lys Ala Met Glu Gln Met
180 185 190
Ala Gly Ser Ser Glu Gln Ala Ala Glu Ala Met Glu Val Ala Ser Gln
195 200 205
Ala Arg Gln Met Val Gln Ala Met Arg Thr Ile Gly Thr His Pro Ser
210 215 220
Ser Ser Thr Gly Leu Lys Asp Asp Leu Leu Glu Asn Leu Gln Ala Tyr
225 230 235 240
Gln Lys Arg Met Gly Val Gln Met Gln Arg Phe Lys
245 250
<210> 64
<211> 291
<212> DNA
<213> 猪流感病毒
<400> 64
atgagtcttc taaccgaggt cgaaacgcct atcagaaacg gatgggagtg caaatgcaac 60
gattcaagtg atcctctcat tgatgccgca agcatcattg ggattttgca cctgatattg 120
tggattcttg atcgtctttt tttcaaatgc atttaccgtc gctttaaata cggtctgcaa 180
agagggcctt ctacggaagg agtgccggag tccatgaggg aagaatatcg gcagaaacag 240
cagagtgctg tggatgttga cgatggtcat tttgtcaaca tagtgctaga g 291
<210> 65
<211> 97
<212> PRT
<213> 猪流感病毒
<400> 65
Met Ser Leu Leu Thr Glu Val Glu Thr Pro Ile Arg Asn Gly Trp Glu
1 5 10 15
Cys Lys Cys Asn Asp Ser Ser Asp Pro Leu Ile Asp Ala Ala Ser Ile
20 25 30
Ile Gly Ile Leu His Leu Ile Leu Trp Ile Leu Asp Arg Leu Phe Phe
35 40 45
Lys Cys Ile Tyr Arg Arg Phe Lys Tyr Gly Leu Gln Arg Gly Pro Ser
50 55 60
Thr Glu Gly Val Pro Glu Ser Met Arg Glu Glu Tyr Arg Gln Lys Gln
65 70 75 80
Gln Ser Ala Val Asp Val Asp Asp Gly His Phe Val Asn Ile Val Leu
85 90 95
Glu
<210> 66
<211> 1407
<212> DNA
<213> 猪流感病毒
<400> 66
atgaatccaa atcaaaagat aataacaatt ggctctgttt ctctcatcat tgccacaata 60
tgcttcttta tgcaaattgc catcctggta actactgtaa cattgcattt caagcagcat 120
gactgcaact cccccccaaa caaccaagta atgctgtgtg aaccaacaat aatagaaaga 180
aacactacag aaattgtgta tttgaccaac accaccatag aaaaggaaat atgccccaaa 240
ctagcagaat acagaaattg gtcaaagccg caatgtaaca tcacaggatt tgcacctttt 300
tctaaggaca attcgattcg actttccgct ggtggagaca tctgggtgac aagagaacct 360
tatgtgtcat gcgatcctga caagtgttat caatttgccc ttgggcaggg aacaacacta 420
aacaacgggc attcaaatga cactgtacat gataggaccc cttaccgaac cctattgatg 480
aatgaattgg gtgttccatt ccatttggga accaggcaag tgtgcatagc atggtccagc 540
tcaagttgtc acgatggaaa agcatggctg catgtttgta taactgggga tgataaaaat 600
gcaactgcta gtttcattta caatgggagg cttgtagata gtattggttc atggtccaaa 660
aatatactca gaacccagga gtcggaatgc gtttgtatca atggaacttg tacagtagta 720
atgactgatg ggagcgcttc aggaaaagct gatactaaaa tactattcat tgaggagggg 780
aaaatcgttc atattagcac attgtcagga agtgctcagc atgtcgagga gtgctcctgt 840
tatcctcgat atcctggtgt cagatgtgtc tgcagagaca actggaaagg ctccaatagg 900
cccatcgtag atataaatgt aaaggattat agcattgttt ccagttatgt atgctcggga 960
cttgttggag acacacccag aaaaaacgac agcttcagca gtagccattg cctagatcct 1020
aacaatgagg aaggtggtca tggagtgaaa ggctgggcct ttgatgatgg aaatgacgtg 1080
tggatgggaa gaacgatcag cgagaagtca cgctcaggtt atgaaacctt caaagtcatc 1140
gaaggctggt ccaaacctaa ttccaaatta cagacaaata ggcaagtcat agttgaaaga 1200
ggtaaaaggt ccggttattc tggtattttc tccgttgaag gcaaaagctg catcaatcgg 1260
tgcttttatg tagagttgat aaggggaagg aaagaggaaa ctaaagtctg gtggacctca 1320
aacagtattg ttgtgttttg tggcacctca ggtacatatg gaacaggctc atggcctgat 1380
ggggcggata tcaatctcat gcctata 1407
<210> 67
<211> 469
<212> PRT
<213> 猪流感病毒
<400> 67
Met Asn Pro Asn Gln Lys Ile Ile Thr Ile Gly Ser Val Ser Leu Ile
1 5 10 15
Ile Ala Thr Ile Cys Phe Phe Met Gln Ile Ala Ile Leu Val Thr Thr
20 25 30
Val Thr Leu His Phe Lys Gln His Asp Cys Asn Ser Pro Pro Asn Asn
35 40 45
Gln Val Met Leu Cys Glu Pro Thr Ile Ile Glu Arg Asn Thr Thr Glu
50 55 60
Ile Val Tyr Leu Thr Asn Thr Thr Ile Glu Lys Glu Ile Cys Pro Lys
65 70 75 80
Leu Ala Glu Tyr Arg Asn Trp Ser Lys Pro Gln Cys Asn Ile Thr Gly
85 90 95
Phe Ala Pro Phe Ser Lys Asp Asn Ser Ile Arg Leu Ser Ala Gly Gly
100 105 110
Asp Ile Trp Val Thr Arg Glu Pro Tyr Val Ser Cys Asp Pro Asp Lys
115 120 125
Cys Tyr Gln Phe Ala Leu Gly Gln Gly Thr Thr Leu Asn Asn Gly His
130 135 140
Ser Asn Asp Thr Val His Asp Arg Thr Pro Tyr Arg Thr Leu Leu Met
145 150 155 160
Asn Glu Leu Gly Val Pro Phe His Leu Gly Thr Arg Gln Val Cys Ile
165 170 175
Ala Trp Ser Ser Ser Ser Cys His Asp Gly Lys Ala Trp Leu His Val
180 185 190
Cys Ile Thr Gly Asp Asp Lys Asn Ala Thr Ala Ser Phe Ile Tyr Asn
195 200 205
Gly Arg Leu Val Asp Ser Ile Gly Ser Trp Ser Lys Asn Ile Leu Arg
210 215 220
Thr Gln Glu Ser Glu Cys Val Cys Ile Asn Gly Thr Cys Thr Val Val
225 230 235 240
Met Thr Asp Gly Ser Ala Ser Gly Lys Ala Asp Thr Lys Ile Leu Phe
245 250 255
Ile Glu Glu Gly Lys Ile Val His Ile Ser Thr Leu Ser Gly Ser Ala
260 265 270
Gln His Val Glu Glu Cys Ser Cys Tyr Pro Arg Tyr Pro Gly Val Arg
275 280 285
Cys Val Cys Arg Asp Asn Trp Lys Gly Ser Asn Arg Pro Ile Val Asp
290 295 300
Ile Asn Val Lys Asp Tyr Ser Ile Val Ser Ser Tyr Val Cys Ser Gly
305 310 315 320
Leu Val Gly Asp Thr Pro Arg Lys Asn Asp Ser Phe Ser Ser Ser His
325 330 335
Cys Leu Asp Pro Asn Asn Glu Glu Gly Gly His Gly Val Lys Gly Trp
340 345 350
Ala Phe Asp Asp Gly Asn Asp Val Trp Met Gly Arg Thr Ile Ser Glu
355 360 365
Lys Ser Arg Ser Gly Tyr Glu Thr Phe Lys Val Ile Glu Gly Trp Ser
370 375 380
Lys Pro Asn Ser Lys Leu Gln Thr Asn Arg Gln Val Ile Val Glu Arg
385 390 395 400
Gly Lys Arg Ser Gly Tyr Ser Gly Ile Phe Ser Val Glu Gly Lys Ser
405 410 415
Cys Ile Asn Arg Cys Phe Tyr Val Glu Leu Ile Arg Gly Arg Lys Glu
420 425 430
Glu Thr Lys Val Trp Trp Thr Ser Asn Ser Ile Val Val Phe Cys Gly
435 440 445
Thr Ser Gly Thr Tyr Gly Thr Gly Ser Trp Pro Asp Gly Ala Asp Ile
450 455 460
Asn Leu Met Pro Ile
465
<210> 68
<211> 1494
<212> DNA
<213> 猪流感病毒
<400> 68
atggcgtctc aaggcaccaa acgatcatat gaacaaatgg agactggtgg tgaacgccaa 60
gatgccacag aaatcagagc atctgtcgga agaatgattg gtggaatcgg gaaattctac 120
atccaaatgt gcactgaact caaactcagt gactatgagg gacgactaat ccaaaatagc 180
ataacaatag agagaatggt gctctctgct tttgatgaga gaagaaataa atacctagaa 240
gagcatccca gtgctgggaa ggatcctaag aaaactggag gacccatata tagaagagta 300
gacggaaagt ggatgagaga actcattctt tatgacaaag aagaaataag gagaatttgg 360
cgccaggcaa acaatggtga tgatgcaaca gctggtctta ctcatatcat gatttggcat 420
tccaatctga atgatgccac gtaccagaga acaagagcac ttgttcgcac cggaatggat 480
cccagaatgt gctctctaat gcaaggttca acacttccca gaaggtctgg ggcagcaggt 540
gctgcagtga aaggagttgg aacaataaca atggaattaa tcagaatgat caaaaggggg 600
atcaatgacc gaaacttctg gagaggtgaa aatggaagaa ggacaaggat tgcatatgaa 660
agaatgtgca atattctcaa aggaaaattt cagacagctg cccaaagggc aatgatggat 720
caagtaagag aaagtcggaa cccaggaaat gctgagattg aagatctcat ttttctggca 780
cggtcagcac ttatcctaag gggatcagtt gcacataagt cttgcctgcc tgcttgtgtg 840
tatgggcttg cagtggcaag tgggcatgac tttgaaaggg aagggtattc gctggtaggg 900
atagacccat ttaaattact ccagaacagt caagtgttca gcctgataag accaaatgaa 960
aacccagctc acaagagtca attagtgtgg atagcatgcc actctgctgc atttgaggat 1020
ctaagggtct caagtttcat aagagggaag aaagtgattc caagggggaa gctttccaca 1080
agagggattc agattgcttc aaatgagaat gtggaagcca tggattccaa taccttagag 1140
ctgagaagca gatactgggc cataaggacc agaagtggag gaaataccaa tcaacagaaa 1200
gcatccgcag gccagatcag tgtgcaacct acattctcag tgcaacggaa tctccctttt 1260
gaaagagcaa ccgttatggc agctttcagc gggaacaatg aaggacggac atccgatatg 1320
cgaacagaaa ttataaggat gatggaaaat gcaaaaccag aagatttgtc cttccagggg 1380
cggggagtct tcgagctctc ggacgaaaag gcaacgagcc cgatcgtgcc ttcctttgac 1440
atgagtaatg aagggtctta tttcttcgga gacaatgcag aggagtatga cagt 1494
<210> 69
<211> 498
<212> PRT
<213> 猪流感病毒
<400> 69
Met Ala Ser Gln Gly Thr Lys Arg Ser Tyr Glu Gln Met Glu Thr Gly
1 5 10 15
Gly Glu Arg Gln Asp Ala Thr Glu Ile Arg Ala Ser Val Gly Arg Met
20 25 30
Ile Gly Gly Ile Gly Lys Phe Tyr Ile Gln Met Cys Thr Glu Leu Lys
35 40 45
Leu Ser Asp Tyr Glu Gly Arg Leu Ile Gln Asn Ser Ile Thr Ile Glu
50 55 60
Arg Met Val Leu Ser Ala Phe Asp Glu Arg Arg Asn Lys Tyr Leu Glu
65 70 75 80
Glu His Pro Ser Ala Gly Lys Asp Pro Lys Lys Thr Gly Gly Pro Ile
85 90 95
Tyr Arg Arg Val Asp Gly Lys Trp Met Arg Glu Leu Ile Leu Tyr Asp
100 105 110
Lys Glu Glu Ile Arg Arg Ile Trp Arg Gln Ala Asn Asn Gly Asp Asp
115 120 125
Ala Thr Ala Gly Leu Thr His Ile Met Ile Trp His Ser Asn Leu Asn
130 135 140
Asp Ala Thr Tyr Gln Arg Thr Arg Ala Leu Val Arg Thr Gly Met Asp
145 150 155 160
Pro Arg Met Cys Ser Leu Met Gln Gly Ser Thr Leu Pro Arg Arg Ser
165 170 175
Gly Ala Ala Gly Ala Ala Val Lys Gly Val Gly Thr Ile Thr Met Glu
180 185 190
Leu Ile Arg Met Ile Lys Arg Gly Ile Asn Asp Arg Asn Phe Trp Arg
195 200 205
Gly Glu Asn Gly Arg Arg Thr Arg Ile Ala Tyr Glu Arg Met Cys Asn
210 215 220
Ile Leu Lys Gly Lys Phe Gln Thr Ala Ala Gln Arg Ala Met Met Asp
225 230 235 240
Gln Val Arg Glu Ser Arg Asn Pro Gly Asn Ala Glu Ile Glu Asp Leu
245 250 255
Ile Phe Leu Ala Arg Ser Ala Leu Ile Leu Arg Gly Ser Val Ala His
260 265 270
Lys Ser Cys Leu Pro Ala Cys Val Tyr Gly Leu Ala Val Ala Ser Gly
275 280 285
His Asp Phe Glu Arg Glu Gly Tyr Ser Leu Val Gly Ile Asp Pro Phe
290 295 300
Lys Leu Leu Gln Asn Ser Gln Val Phe Ser Leu Ile Arg Pro Asn Glu
305 310 315 320
Asn Pro Ala His Lys Ser Gln Leu Val Trp Ile Ala Cys His Ser Ala
325 330 335
Ala Phe Glu Asp Leu Arg Val Ser Ser Phe Ile Arg Gly Lys Lys Val
340 345 350
Ile Pro Arg Gly Lys Leu Ser Thr Arg Gly Ile Gln Ile Ala Ser Asn
355 360 365
Glu Asn Val Glu Ala Met Asp Ser Asn Thr Leu Glu Leu Arg Ser Arg
370 375 380
Tyr Trp Ala Ile Arg Thr Arg Ser Gly Gly Asn Thr Asn Gln Gln Lys
385 390 395 400
Ala Ser Ala Gly Gln Ile Ser Val Gln Pro Thr Phe Ser Val Gln Arg
405 410 415
Asn Leu Pro Phe Glu Arg Ala Thr Val Met Ala Ala Phe Ser Gly Asn
420 425 430
Asn Glu Gly Arg Thr Ser Asp Met Arg Thr Glu Ile Ile Arg Met Met
435 440 445
Glu Asn Ala Lys Pro Glu Asp Leu Ser Phe Gln Gly Arg Gly Val Phe
450 455 460
Glu Leu Ser Asp Glu Lys Ala Thr Ser Pro Ile Val Pro Ser Phe Asp
465 470 475 480
Met Ser Asn Glu Gly Ser Tyr Phe Phe Gly Asp Asn Ala Glu Glu Tyr
485 490 495
Asp Ser
<210> 70
<211> 1698
<212> DNA
<213> 猪流感病毒
<400> 70
atgaagacta tcattgcttt tagctacatt ttatgtctga ttttcgctca aaaacttccc 60
ggaagtgaca acagcatggc aacgctatgc ctaggacacc atgcagtacc aaacggaacg 120
ttagtgaaaa caatcacgga tgaccaaatt gaagtgacta atgctactga gctggtccaa 180
agttcctcaa caggtagaat atgcaacagt cctcaccaaa tccttgatgg gaaaaattgc 240
acactgatag atgctctatt gggagaccct cattgtgatg acttccaaaa caaggaatgg 300
gacctttttg ttgaacgaag cacagcctac agcaactgct acccttatta tgtgccggat 360
tatgcctccc ttaggtcact agttgcctca tccggcaccc tggaattcac ccaagaaagc 420
ttcaattgga ctggagttgc tcaagatgga tcaagctatg cttgcagaag gaaatctgtt 480
aacagtttct ttagtagatt aaattggttg cataatctga attacaaata tccagcgctg 540
aacgtaacta tgccaaacaa tgacaaattt gacaaattgt acatttgggg ggttcaccac 600
ccgggtacgg acagggacca aaccaaccta tatgttcaag catcagggag ggttacagtc 660
tccaccaaaa gaagccaaca aactgtaatc ccgaatatcg gatctagacc ctgggtaagg 720
ggtgtctcca gcataataag catctattgg acaatagtaa aaccgggaga catacttttg 780
attaacagca cagggaatct aattgcccct cggggttact tcaaaataca aagtgggaaa 840
agctcaataa tgaggtcaga tgcacccatt ggcaactgca attctgaatg cattactcca 900
aatggaagca ttcccaatga caaacctttt caaaatgtaa acaggatcac atatggggcc 960
tgtcccagat atgtgaagca aaacactctg aaattggcaa cagggatgcg gaatgtacca 1020
gagaaacaaa ctagaggcat attcggcgca atcgcaggtt tcatagaaaa tggttgggag 1080
gggatggtgg acggttggta cggtttcagg catcaaaatt ctgaaggcac aggacaagca 1140
gcagatctta aaagcactca agcagcagtc aaccaaatca ccgggaaact aaatagagta 1200
atcaagaaaa cgaacgagaa attccatcag atcgaaaaag aattctcaga agtagaaggg 1260
agaattcagg acctagagaa atacgttgaa gacactaaaa tagatctctg gtcttacaac 1320
gcggagcttc ttgttgccct ggagaaccaa catacaattg atttaactga ctcagaaatg 1380
aacaaactgt tcgaaagaac aaggaagcaa ctgcgggaaa atgctgagga catgggcaat 1440
ggttgcttca aaatatacca caagtgtgac aatgcctgca taggatcaat cagaaatgga 1500
acttatgacc atgatgtata cagagacgag gcattaaaca atcgattcca gatcaaaggt 1560
gttcagctga agtcaggata caaagattgg atcctatgga tttcctttgc catatcatgc 1620
tttttgcttt gtgttgttct gctggggttc atcatgtggg cctgccaaaa aggcaacatt 1680
aggtgcaaca tttgcatt 1698
<210> 71
<211> 566
<212> PRT
<213> 猪流感病毒
<400> 71
Met Lys Thr Ile Ile Ala Phe Ser Tyr Ile Leu Cys Leu Ile Phe Ala
1 5 10 15
Gln Lys Leu Pro Gly Ser Asp Asn Ser Met Ala Thr Leu Cys Leu Gly
20 25 30
His His Ala Val Pro Asn Gly Thr Leu Val Lys Thr Ile Thr Asp Asp
35 40 45
Gln Ile Glu Val Thr Asn Ala Thr Glu Leu Val Gln Ser Ser Ser Thr
50 55 60
Gly Arg Ile Cys Asn Ser Pro His Gln Ile Leu Asp Gly Lys Asn Cys
65 70 75 80
Thr Leu Ile Asp Ala Leu Leu Gly Asp Pro His Cys Asp Asp Phe Gln
85 90 95
Asn Lys Glu Trp Asp Leu Phe Val Glu Arg Ser Thr Ala Tyr Ser Asn
100 105 110
Cys Tyr Pro Tyr Tyr Val Pro Asp Tyr Ala Ser Leu Arg Ser Leu Val
115 120 125
Ala Ser Ser Gly Thr Leu Glu Phe Thr Gln Glu Ser Phe Asn Trp Thr
130 135 140
Gly Val Ala Gln Asp Gly Ser Ser Tyr Ala Cys Arg Arg Lys Ser Val
145 150 155 160
Asn Ser Phe Phe Ser Arg Leu Asn Trp Leu His Asn Leu Asn Tyr Lys
165 170 175
Tyr Pro Ala Leu Asn Val Thr Met Pro Asn Asn Asp Lys Phe Asp Lys
180 185 190
Leu Tyr Ile Trp Gly Val His His Pro Gly Thr Asp Arg Asp Gln Thr
195 200 205
Asn Leu Tyr Val Gln Ala Ser Gly Arg Val Thr Val Ser Thr Lys Arg
210 215 220
Ser Gln Gln Thr Val Ile Pro Asn Ile Gly Ser Arg Pro Trp Val Arg
225 230 235 240
Gly Val Ser Ser Ile Ile Ser Ile Tyr Trp Thr Ile Val Lys Pro Gly
245 250 255
Asp Ile Leu Leu Ile Asn Ser Thr Gly Asn Leu Ile Ala Pro Arg Gly
260 265 270
Tyr Phe Lys Ile Gln Ser Gly Lys Ser Ser Ile Met Arg Ser Asp Ala
275 280 285
Pro Ile Gly Asn Cys Asn Ser Glu Cys Ile Thr Pro Asn Gly Ser Ile
290 295 300
Pro Asn Asp Lys Pro Phe Gln Asn Val Asn Arg Ile Thr Tyr Gly Ala
305 310 315 320
Cys Pro Arg Tyr Val Lys Gln Asn Thr Leu Lys Leu Ala Thr Gly Met
325 330 335
Arg Asn Val Pro Glu Lys Gln Thr Arg Gly Ile Phe Gly Ala Ile Ala
340 345 350
Gly Phe Ile Glu Asn Gly Trp Glu Gly Met Val Asp Gly Trp Tyr Gly
355 360 365
Phe Arg His Gln Asn Ser Glu Gly Thr Gly Gln Ala Ala Asp Leu Lys
370 375 380
Ser Thr Gln Ala Ala Val Asn Gln Ile Thr Gly Lys Leu Asn Arg Val
385 390 395 400
Ile Lys Lys Thr Asn Glu Lys Phe His Gln Ile Glu Lys Glu Phe Ser
405 410 415
Glu Val Glu Gly Arg Ile Gln Asp Leu Glu Lys Tyr Val Glu Asp Thr
420 425 430
Lys Ile Asp Leu Trp Ser Tyr Asn Ala Glu Leu Leu Val Ala Leu Glu
435 440 445
Asn Gln His Thr Ile Asp Leu Thr Asp Ser Glu Met Asn Lys Leu Phe
450 455 460
Glu Arg Thr Arg Lys Gln Leu Arg Glu Asn Ala Glu Asp Met Gly Asn
465 470 475 480
Gly Cys Phe Lys Ile Tyr His Lys Cys Asp Asn Ala Cys Ile Gly Ser
485 490 495
Ile Arg Asn Gly Thr Tyr Asp His Asp Val Tyr Arg Asp Glu Ala Leu
500 505 510
Asn Asn Arg Phe Gln Ile Lys Gly Val Gln Leu Lys Ser Gly Tyr Lys
515 520 525
Asp Trp Ile Leu Trp Ile Ser Phe Ala Ile Ser Cys Phe Leu Leu Cys
530 535 540
Val Val Leu Leu Gly Phe Ile Met Trp Ala Cys Gln Lys Gly Asn Ile
545 550 555 560
Arg Cys Asn Ile Cys Ile
565
<210> 72
<211> 2148
<212> DNA
<213> 猪流感病毒
<400> 72
atggaagact ttgtgcgaca atgcttcaat ccaatgatcg tcgagcttgc ggaaaaggca 60
atgaaagaat atggagagga ttcgaaaatc gaaaccaaca aattcgctgc aatatgcacg 120
cacttggaag tctgtttcat gtattcggat ttccatttca ttgacgaaca gggtgaatca 180
atcattatag aatctggtga tccaaatgca ttgctgaagc accgatttga gataattgaa 240
ggaagagaca ggactatggc ctggacagta gtgaacagta tctgcaacac cacaggggta 300
gagaagccta aatttcttcc ggatttatac gactacaaag aaaaccgatt cgttgaaatt 360
ggagtgacac gaagggaggt ccacatatac tacctagaga aagccaacaa gataaaatcc 420
gagaagacac acattcatat tttttcattc actggagagg agatggccac caaagcggac 480
tacacccttg atgaagagag cagggcaaga atcaaaacca ggctcttcac cataagacaa 540
gagatggcca gtaggggtct atgggattcc tttcgtcagt ccgagagagg cgaagagaca 600
attgaagaaa gatttgaaat tacaggaacc atgcgcaggc ttgccgacca aagtctccca 660
ccgaacttct ccagccttga aaactttaga gcctatgtag atgggttcga accaaacggc 720
tgcattgagg gcaagctttc tcaaatgtca aaagaagtga gtgcccaaat tgaaccattc 780
ttgaagacaa caccacaccc tctcagattg cctaatgggc ctccttgctc tcagcggtca 840
aagttcttgc tgatggatgc tctgaaacta agtattgaag acccgagtca tgagggagaa 900
ggaataccac tatatgatgc aatcaagtgc atgaagacat tttttggctg gaaagagcct 960
aacataatca aaccacatga gaaaggcata aaccccaatt atctactggc ttggaagcag 1020
gtgctagcag agctccagga cattgaaaat gaagagaaga tcccaaagac aaagaacatg 1080
aagagaacaa gccaattgaa gtgggcactt ggtgagaata tggcaccaga gaaagtagat 1140
tttgatgact gcaaagatgt cggtgatctc aaacagtatg acagcgatga gccagagccc 1200
agatctctag caagctgggt ccaaaatgag ttcaacaagg catgtgaatt gaccgattca 1260
agctggatag aacttgatga gataggagaa gatgttgccc cgattgaaca catcgcaagc 1320
atgaggagga actattttac agcagaagtg tcccattgca gggctactga atacataatg 1380
aagggagtgt acataaatac ggctctactt aatgcatctt gtgcagccat ggatgacttt 1440
cagctgatcc caatgataag caaatgtaga accaaagaag gaagacgaaa aacaaatctg 1500
tatggtttca ttataaaagg aaggtcccat ctgagaaatg atactgacgt ggtgaacttt 1560
gtaagcatgg agttctccct cactgacccg agactggagc cacacaaatg ggaaaagtac 1620
tgtgttcttg aaataggaga catgctcctg aggactgcga taggccaagt gtcgaggccc 1680
atgttcctat atgtgagaac caatggaacc tccaagatca agatgaaatg gggcatggaa 1740
atgaggcgct gcctcctcca gtctcttcag cagattgaga gcatgattga ggctgagtct 1800
tctgtcaaag agaaagacat gaccaaggaa ttctttgaaa acaaatcgga aacatggcca 1860
atcggagaat cacccaaagg agtggaggaa ggctctattg ggaaagtgtg caggacctta 1920
ctggcaaaat ctgtattcaa cagtctatac gcgtctccac aacttgaagg gttttcggct 1980
gaatcgagaa aattgctcct cattgttcag gcacttaggg acaacttgga acctggaacc 2040
ttcgatcttg gggggctata tgaagcaatc gaggagtgcc tgattaatga tccctgggtt 2100
ttgcttaatg catcttggtt caactccttc ctcacacatg cactgaaa 2148
<210> 73
<211> 716
<212> PRT
<213> 猪流感病毒
<400> 73
Met Glu Asp Phe Val Arg Gln Cys Phe Asn Pro Met Ile Val Glu Leu
1 5 10 15
Ala Glu Lys Ala Met Lys Glu Tyr Gly Glu Asp Ser Lys Ile Glu Thr
20 25 30
Asn Lys Phe Ala Ala Ile Cys Thr His Leu Glu Val Cys Phe Met Tyr
35 40 45
Ser Asp Phe His Phe Ile Asp Glu Gln Gly Glu Ser Ile Ile Ile Glu
50 55 60
Ser Gly Asp Pro Asn Ala Leu Leu Lys His Arg Phe Glu Ile Ile Glu
65 70 75 80
Gly Arg Asp Arg Thr Met Ala Trp Thr Val Val Asn Ser Ile Cys Asn
85 90 95
Thr Thr Gly Val Glu Lys Pro Lys Phe Leu Pro Asp Leu Tyr Asp Tyr
100 105 110
Lys Glu Asn Arg Phe Val Glu Ile Gly Val Thr Arg Arg Glu Val His
115 120 125
Ile Tyr Tyr Leu Glu Lys Ala Asn Lys Ile Lys Ser Glu Lys Thr His
130 135 140
Ile His Ile Phe Ser Phe Thr Gly Glu Glu Met Ala Thr Lys Ala Asp
145 150 155 160
Tyr Thr Leu Asp Glu Glu Ser Arg Ala Arg Ile Lys Thr Arg Leu Phe
165 170 175
Thr Ile Arg Gln Glu Met Ala Ser Arg Gly Leu Trp Asp Ser Phe Arg
180 185 190
Gln Ser Glu Arg Gly Glu Glu Thr Ile Glu Glu Arg Phe Glu Ile Thr
195 200 205
Gly Thr Met Arg Arg Leu Ala Asp Gln Ser Leu Pro Pro Asn Phe Ser
210 215 220
Ser Leu Glu Asn Phe Arg Ala Tyr Val Asp Gly Phe Glu Pro Asn Gly
225 230 235 240
Cys Ile Glu Gly Lys Leu Ser Gln Met Ser Lys Glu Val Ser Ala Gln
245 250 255
Ile Glu Pro Phe Leu Lys Thr Thr Pro His Pro Leu Arg Leu Pro Asn
260 265 270
Gly Pro Pro Cys Ser Gln Arg Ser Lys Phe Leu Leu Met Asp Ala Leu
275 280 285
Lys Leu Ser Ile Glu Asp Pro Ser His Glu Gly Glu Gly Ile Pro Leu
290 295 300
Tyr Asp Ala Ile Lys Cys Met Lys Thr Phe Phe Gly Trp Lys Glu Pro
305 310 315 320
Asn Ile Ile Lys Pro His Glu Lys Gly Ile Asn Pro Asn Tyr Leu Leu
325 330 335
Ala Trp Lys Gln Val Leu Ala Glu Leu Gln Asp Ile Glu Asn Glu Glu
340 345 350
Lys Ile Pro Lys Thr Lys Asn Met Lys Arg Thr Ser Gln Leu Lys Trp
355 360 365
Ala Leu Gly Glu Asn Met Ala Pro Glu Lys Val Asp Phe Asp Asp Cys
370 375 380
Lys Asp Val Gly Asp Leu Lys Gln Tyr Asp Ser Asp Glu Pro Glu Pro
385 390 395 400
Arg Ser Leu Ala Ser Trp Val Gln Asn Glu Phe Asn Lys Ala Cys Glu
405 410 415
Leu Thr Asp Ser Ser Trp Ile Glu Leu Asp Glu Ile Gly Glu Asp Val
420 425 430
Ala Pro Ile Glu His Ile Ala Ser Met Arg Arg Asn Tyr Phe Thr Ala
435 440 445
Glu Val Ser His Cys Arg Ala Thr Glu Tyr Ile Met Lys Gly Val Tyr
450 455 460
Ile Asn Thr Ala Leu Leu Asn Ala Ser Cys Ala Ala Met Asp Asp Phe
465 470 475 480
Gln Leu Ile Pro Met Ile Ser Lys Cys Arg Thr Lys Glu Gly Arg Arg
485 490 495
Lys Thr Asn Leu Tyr Gly Phe Ile Ile Lys Gly Arg Ser His Leu Arg
500 505 510
Asn Asp Thr Asp Val Val Asn Phe Val Ser Met Glu Phe Ser Leu Thr
515 520 525
Asp Pro Arg Leu Glu Pro His Lys Trp Glu Lys Tyr Cys Val Leu Glu
530 535 540
Ile Gly Asp Met Leu Leu Arg Thr Ala Ile Gly Gln Val Ser Arg Pro
545 550 555 560
Met Phe Leu Tyr Val Arg Thr Asn Gly Thr Ser Lys Ile Lys Met Lys
565 570 575
Trp Gly Met Glu Met Arg Arg Cys Leu Leu Gln Ser Leu Gln Gln Ile
580 585 590
Glu Ser Met Ile Glu Ala Glu Ser Ser Val Lys Glu Lys Asp Met Thr
595 600 605
Lys Glu Phe Phe Glu Asn Lys Ser Glu Thr Trp Pro Ile Gly Glu Ser
610 615 620
Pro Lys Gly Val Glu Glu Gly Ser Ile Gly Lys Val Cys Arg Thr Leu
625 630 635 640
Leu Ala Lys Ser Val Phe Asn Ser Leu Tyr Ala Ser Pro Gln Leu Glu
645 650 655
Gly Phe Ser Ala Glu Ser Arg Lys Leu Leu Leu Ile Val Gln Ala Leu
660 665 670
Arg Asp Asn Leu Glu Pro Gly Thr Phe Asp Leu Gly Gly Leu Tyr Glu
675 680 685
Ala Ile Glu Glu Cys Leu Ile Asn Asp Pro Trp Val Leu Leu Asn Ala
690 695 700
Ser Trp Phe Asn Ser Phe Leu Thr His Ala Leu Lys
705 710 715
<210> 74
<211> 2271
<212> DNA
<213> 猪流感病毒
<400> 74
atggatgtca atccgactct acttttccta aaggttccag cgcagaatgc cataagcacc 60
acattccctt atactggaga tcctccatac agccatggaa caggaacagg atacaccatg 120
gacacagtca acagaacaca ccaatattca gaaaaaggga aatggacgac aaacacagag 180
actggggcac cccagctcaa tccgattgat ggaccactac ctgaagataa tgaaccaagt 240
ggatatgcac aaacagactg tgttctggag gccatggctt tccttgaaga atcccaccca 300
gggatatttg agaattcatg ccttgaaaca atggaaattg tccaacaaac aagggtggat 360
aaactaactc agggtcgcca gacttatgat tggacattga atagaaatca accggcagca 420
actgcattgg ccaacaccat agaagttttt agatcaaatg gtctaacagc taatgagtca 480
ggaaggctaa tagatttctt aaaagatgta atggaatcaa tggataaaga ggaaatagag 540
ataacgacac actttcaaag aaaaaggaga ataagggaca acatgaccaa gaagatggtc 600
acgcaaagaa caatagggaa gaaaaaacaa agagtgtata agaaaagtta tctaataaga 660
gcactgacat tgaatacgat gaccaaagat gcagagagag gcaaattaaa aaggagggct 720
attgcaacac ctgggatgca aattagaggg ttcgtgtact ttgttgagac tttagctaga 780
agcatttgcg aaaagcttga acagtccgga ctcccagtag ggggcaatga aaagaaagct 840
aaattggcaa acgttgtgag aaagatgatg actaattcac aagacacaga gctttctttc 900
acaatcactg gggacaacac taaatggaat gaaaaccaaa atcctcgaat gttcctggcg 960
atgattacat acatcaccag aaatcaaccc gagtggttca gaaacatcct gagcatggca 1020
cccataatgt tctcaaacaa aatggcaaga ctagggaaag ggtacatgtt cgagagtaaa 1080
agaatgaggc tccgaacaca gataccagca gaaatgctag caagcattga cctgaagtat 1140
ttcaatgaat caacaaagaa gaaaattgag aaaataaggc ctctcctaat agatggcaca 1200
gcatcattga gccctgggat gatgatgggc atgttcaaca tgctaagtac ggttttggga 1260
gtctcgatac tgaatcttgg acaaaagaaa tacacaagga caacatactg gtgggacgga 1320
ctccaatcct ccgacgattt tgccctcata gtaaatgcac caaatcatga gggaatacaa 1380
gcaggagtgg atagattcta caggacctgc aagttagtag gaatcaacat gagcaaaaag 1440
aagtcctata taaataagac tgggacattt gaattcacaa gcttttttta tcgctatggg 1500
tttgtagcta attttagcat ggagctgccc agttttggag tgtctggaat aaacgaatca 1560
gctgatatga gtattggagt aacagtgata aagaacaaca tgataaacaa tgatcttgga 1620
cctgcaacag cccagatggc ccttcagttg ttcatcaaag actacagata cacatataga 1680
tgccatagag gggacacaca aatccagacg agaagatcat tcgagctaaa gaagctgtgg 1740
gatcaaaccc aatcaaaggc aggattatta gtatctgatg gaggaccaaa tttatacaat 1800
atccggaatc ttcacattcc tgaagtctgc ttaaaatggg agctaatgga tgaggattac 1860
cggggaagac tttgcaatcc cctgaatccc tttgtcagcc ataaagagat tgattctgta 1920
aacagtgctg tggtgatgcc agcccatggt ccagccaaaa gcatggaata tgatgccgtt 1980
acaactacac actcctggat tcccaagagg aaccgctcta ttctcaacac aagccaaagg 2040
ggaattcttg aggatgaaca gatgtaccag aagtgctgca acctgttcga gaaatttttc 2100
cctagtagtt catacaggag accggttgga atttctagca tggtagaggc catggtgtct 2160
agggcccgga ttgatgccag gattgacttc gagtctggac ggattaagaa agaagagttc 2220
tctgagatca tgaagatctg ttccaccatt gaagaactca gacggcaaaa g 2271
<210> 75
<211> 757
<212> PRT
<213> 猪流感病毒
<400> 75
Met Asp Val Asn Pro Thr Leu Leu Phe Leu Lys Val Pro Ala Gln Asn
1 5 10 15
Ala Ile Ser Thr Thr Phe Pro Tyr Thr Gly Asp Pro Pro Tyr Ser His
20 25 30
Gly Thr Gly Thr Gly Tyr Thr Met Asp Thr Val Asn Arg Thr His Gln
35 40 45
Tyr Ser Glu Lys Gly Lys Trp Thr Thr Asn Thr Glu Thr Gly Ala Pro
50 55 60
Gln Leu Asn Pro Ile Asp Gly Pro Leu Pro Glu Asp Asn Glu Pro Ser
65 70 75 80
Gly Tyr Ala Gln Thr Asp Cys Val Leu Glu Ala Met Ala Phe Leu Glu
85 90 95
Glu Ser His Pro Gly Ile Phe Glu Asn Ser Cys Leu Glu Thr Met Glu
100 105 110
Ile Val Gln Gln Thr Arg Val Asp Lys Leu Thr Gln Gly Arg Gln Thr
115 120 125
Tyr Asp Trp Thr Leu Asn Arg Asn Gln Pro Ala Ala Thr Ala Leu Ala
130 135 140
Asn Thr Ile Glu Val Phe Arg Ser Asn Gly Leu Thr Ala Asn Glu Ser
145 150 155 160
Gly Arg Leu Ile Asp Phe Leu Lys Asp Val Met Glu Ser Met Asp Lys
165 170 175
Glu Glu Ile Glu Ile Thr Thr His Phe Gln Arg Lys Arg Arg Ile Arg
180 185 190
Asp Asn Met Thr Lys Lys Met Val Thr Gln Arg Thr Ile Gly Lys Lys
195 200 205
Lys Gln Arg Val Tyr Lys Lys Ser Tyr Leu Ile Arg Ala Leu Thr Leu
210 215 220
Asn Thr Met Thr Lys Asp Ala Glu Arg Gly Lys Leu Lys Arg Arg Ala
225 230 235 240
Ile Ala Thr Pro Gly Met Gln Ile Arg Gly Phe Val Tyr Phe Val Glu
245 250 255
Thr Leu Ala Arg Ser Ile Cys Glu Lys Leu Glu Gln Ser Gly Leu Pro
260 265 270
Val Gly Gly Asn Glu Lys Lys Ala Lys Leu Ala Asn Val Val Arg Lys
275 280 285
Met Met Thr Asn Ser Gln Asp Thr Glu Leu Ser Phe Thr Ile Thr Gly
290 295 300
Asp Asn Thr Lys Trp Asn Glu Asn Gln Asn Pro Arg Met Phe Leu Ala
305 310 315 320
Met Ile Thr Tyr Ile Thr Arg Asn Gln Pro Glu Trp Phe Arg Asn Ile
325 330 335
Leu Ser Met Ala Pro Ile Met Phe Ser Asn Lys Met Ala Arg Leu Gly
340 345 350
Lys Gly Tyr Met Phe Glu Ser Lys Arg Met Arg Leu Arg Thr Gln Ile
355 360 365
Pro Ala Glu Met Leu Ala Ser Ile Asp Leu Lys Tyr Phe Asn Glu Ser
370 375 380
Thr Lys Lys Lys Ile Glu Lys Ile Arg Pro Leu Leu Ile Asp Gly Thr
385 390 395 400
Ala Ser Leu Ser Pro Gly Met Met Met Gly Met Phe Asn Met Leu Ser
405 410 415
Thr Val Leu Gly Val Ser Ile Leu Asn Leu Gly Gln Lys Lys Tyr Thr
420 425 430
Arg Thr Thr Tyr Trp Trp Asp Gly Leu Gln Ser Ser Asp Asp Phe Ala
435 440 445
Leu Ile Val Asn Ala Pro Asn His Glu Gly Ile Gln Ala Gly Val Asp
450 455 460
Arg Phe Tyr Arg Thr Cys Lys Leu Val Gly Ile Asn Met Ser Lys Lys
465 470 475 480
Lys Ser Tyr Ile Asn Lys Thr Gly Thr Phe Glu Phe Thr Ser Phe Phe
485 490 495
Tyr Arg Tyr Gly Phe Val Ala Asn Phe Ser Met Glu Leu Pro Ser Phe
500 505 510
Gly Val Ser Gly Ile Asn Glu Ser Ala Asp Met Ser Ile Gly Val Thr
515 520 525
Val Ile Lys Asn Asn Met Ile Asn Asn Asp Leu Gly Pro Ala Thr Ala
530 535 540
Gln Met Ala Leu Gln Leu Phe Ile Lys Asp Tyr Arg Tyr Thr Tyr Arg
545 550 555 560
Cys His Arg Gly Asp Thr Gln Ile Gln Thr Arg Arg Ser Phe Glu Leu
565 570 575
Lys Lys Leu Trp Asp Gln Thr Gln Ser Lys Ala Gly Leu Leu Val Ser
580 585 590
Asp Gly Gly Pro Asn Leu Tyr Asn Ile Arg Asn Leu His Ile Pro Glu
595 600 605
Val Cys Leu Lys Trp Glu Leu Met Asp Glu Asp Tyr Arg Gly Arg Leu
610 615 620
Cys Asn Pro Leu Asn Pro Phe Val Ser His Lys Glu Ile Asp Ser Val
625 630 635 640
Asn Ser Ala Val Val Met Pro Ala His Gly Pro Ala Lys Ser Met Glu
645 650 655
Tyr Asp Ala Val Thr Thr Thr His Ser Trp Ile Pro Lys Arg Asn Arg
660 665 670
Ser Ile Leu Asn Thr Ser Gln Arg Gly Ile Leu Glu Asp Glu Gln Met
675 680 685
Tyr Gln Lys Cys Cys Asn Leu Phe Glu Lys Phe Phe Pro Ser Ser Ser
690 695 700
Tyr Arg Arg Pro Val Gly Ile Ser Ser Met Val Glu Ala Met Val Ser
705 710 715 720
Arg Ala Arg Ile Asp Ala Arg Ile Asp Phe Glu Ser Gly Arg Ile Lys
725 730 735
Lys Glu Glu Phe Ser Glu Ile Met Lys Ile Cys Ser Thr Ile Glu Glu
740 745 750
Leu Arg Arg Gln Lys
755
<210> 76
<211> 2277
<212> DNA
<213> 猪流感病毒
<400> 76
atggagagaa taaaagaact aagagatcta atgtcgcagt cccgcactcg cgagatactc 60
actaagacca ctgtggacca tatggccata atcaaaaagt acacatcagg aaggcaagag 120
aagaaccccg cactcagaat gaagtggatg atggcaatga aatacccaat tacagcagac 180
aagagaataa tggacatgat tccagagagg aatgaacaag gacaaaccct ctggagcaaa 240
acaaacgatg ctggatcgga ccgtgtgatg gtatcacccc tggccgtaac atggtggaat 300
aggaatggcc caacaacaag cacagttcac taccctaagg tatataaaac ttatttcgaa 360
aaagtcgaaa ggttaaaaca tggtaccttt ggccctgtcc acttcagaaa tcaagttaaa 420
ataagaagga gggttgacac aaaccctggt catgcagatc tcagtgccaa ggaggcacag 480
gatgtgatca tggaagttgt tttcccaaat gaagtggggg caagaatact gacatcagag 540
tcacagctga caataacaaa agaaaagaaa gaagaactcc aggattgtaa aattgctccc 600
ttgatggtgg catacatgct agaaagagag ttggttcgta agacgaggtt tctcccggtg 660
gcaggtggaa caagcagtgt ttatattgaa gtgctgcact taactcaggg aacatgctgg 720
gagcaaatgt acactccagg aggagaagtg agaaatgatg atgttgacca aagtttgatt 780
atcgctgcta gaaacatagt aagaagagca gcagtgtcag cagacccatt agcatctctc 840
ttggaaatgt gccacagcac acagattgga ggaataagga tggtggacat ccttagacag 900
aacccaacgg aggaacaagc cgtagacata tgcaaggcag caatggggct gaggattagc 960
tcctctttca gctttggtgg gttcaccttc aaaagaacaa gcggatcatc agttaagaag 1020
gaagaagaag tgctcacggg caacctccaa acactgaaaa taagagtaca tgaaggatat 1080
gaagaattca caatggtcgg gaaaagagca acagctattc tcagaaaagc aaccaggagg 1140
ttgatccagt taatagtaag tgggagagac gatcaatcaa ttgctgaggc aataattgtg 1200
gccatggtat tttcacaaga ggattgcatg atcaaggcag ttaggggcga tctgaacttt 1260
gtcaataggg caaaccagcg actgaatccc atgcaccaac tcttgaggca tttccaaaaa 1320
gatgcaaaag tgcttttcca gaactgggga attgaaccca tcgacagtgt gatgggaatg 1380
atcgggatat tgcctgatat gaccccaagc acggaaatgt cgctgagagg tataagagtc 1440
agcaaaatgg gagtagatga gtattccagc acggagagag tggtagtgag cattgaccga 1500
tttttgagag ttcgggatca acgagggaac gtactattgt ctcccgaaga ggtcagcgag 1560
acacaaggaa ctgagaaatt gacaataact tattcgtcat caatgatgtg ggagatcaat 1620
ggtcctgagt cagtgctggt caacacttat caatggatca taaggaactg ggaaagcttg 1680
aaaattcaat ggtcacaaga tcccacgatg ttatacaaca aaatggaatt tgaaccattc 1740
cagtctcttg tccctaaggc aatcagaagt cgttacagtg gattcgtaag gacactgttc 1800
cagcaaatgc gggatgtgct tggaacattt gacactgtcc aaataataaa actcctcccc 1860
tttgctgctg ctccacctga acagagtagg atgcagttct cctcgctgac tgtgaatgtg 1920
agaggatcag ggctgaggat actggtaaga ggcaattctc cagtgttcaa ttacaacaaa 1980
gcaaccaaaa ggcttacaat tcttgggaaa gatgcaggtg cattgactga agatccagat 2040
gaaggcacag ctggagtgga gtctgctgtc ctgaggggat tcctcatttt gggtaaagaa 2100
gacaagagat atggcccagc attaagcatc aatgaactga gcaatcttgc aaaaggggag 2160
aaggctaatg tgctaattgg gcaaggagac gtggtgttgg taatgaaacg gaaacgggac 2220
tctagcatac ttactgacag ccagacagcg accaaaagaa ttcggatggc catcaat 2277
<210> 77
<211> 759
<212> PRT
<213> 猪流感病毒
<400> 77
Met Glu Arg Ile Lys Glu Leu Arg Asp Leu Met Ser Gln Ser Arg Thr
1 5 10 15
Arg Glu Ile Leu Thr Lys Thr Thr Val Asp His Met Ala Ile Ile Lys
20 25 30
Lys Tyr Thr Ser Gly Arg Gln Glu Lys Asn Pro Ala Leu Arg Met Lys
35 40 45
Trp Met Met Ala Met Lys Tyr Pro Ile Thr Ala Asp Lys Arg Ile Met
50 55 60
Asp Met Ile Pro Glu Arg Asn Glu Gln Gly Gln Thr Leu Trp Ser Lys
65 70 75 80
Thr Asn Asp Ala Gly Ser Asp Arg Val Met Val Ser Pro Leu Ala Val
85 90 95
Thr Trp Trp Asn Arg Asn Gly Pro Thr Thr Ser Thr Val His Tyr Pro
100 105 110
Lys Val Tyr Lys Thr Tyr Phe Glu Lys Val Glu Arg Leu Lys His Gly
115 120 125
Thr Phe Gly Pro Val His Phe Arg Asn Gln Val Lys Ile Arg Arg Arg
130 135 140
Val Asp Thr Asn Pro Gly His Ala Asp Leu Ser Ala Lys Glu Ala Gln
145 150 155 160
Asp Val Ile Met Glu Val Val Phe Pro Asn Glu Val Gly Ala Arg Ile
165 170 175
Leu Thr Ser Glu Ser Gln Leu Thr Ile Thr Lys Glu Lys Lys Glu Glu
180 185 190
Leu Gln Asp Cys Lys Ile Ala Pro Leu Met Val Ala Tyr Met Leu Glu
195 200 205
Arg Glu Leu Val Arg Lys Thr Arg Phe Leu Pro Val Ala Gly Gly Thr
210 215 220
Ser Ser Val Tyr Ile Glu Val Leu His Leu Thr Gln Gly Thr Cys Trp
225 230 235 240
Glu Gln Met Tyr Thr Pro Gly Gly Glu Val Arg Asn Asp Asp Val Asp
245 250 255
Gln Ser Leu Ile Ile Ala Ala Arg Asn Ile Val Arg Arg Ala Ala Val
260 265 270
Ser Ala Asp Pro Leu Ala Ser Leu Leu Glu Met Cys His Ser Thr Gln
275 280 285
Ile Gly Gly Ile Arg Met Val Asp Ile Leu Arg Gln Asn Pro Thr Glu
290 295 300
Glu Gln Ala Val Asp Ile Cys Lys Ala Ala Met Gly Leu Arg Ile Ser
305 310 315 320
Ser Ser Phe Ser Phe Gly Gly Phe Thr Phe Lys Arg Thr Ser Gly Ser
325 330 335
Ser Val Lys Lys Glu Glu Glu Val Leu Thr Gly Asn Leu Gln Thr Leu
340 345 350
Lys Ile Arg Val His Glu Gly Tyr Glu Glu Phe Thr Met Val Gly Lys
355 360 365
Arg Ala Thr Ala Ile Leu Arg Lys Ala Thr Arg Arg Leu Ile Gln Leu
370 375 380
Ile Val Ser Gly Arg Asp Asp Gln Ser Ile Ala Glu Ala Ile Ile Val
385 390 395 400
Ala Met Val Phe Ser Gln Glu Asp Cys Met Ile Lys Ala Val Arg Gly
405 410 415
Asp Leu Asn Phe Val Asn Arg Ala Asn Gln Arg Leu Asn Pro Met His
420 425 430
Gln Leu Leu Arg His Phe Gln Lys Asp Ala Lys Val Leu Phe Gln Asn
435 440 445
Trp Gly Ile Glu Pro Ile Asp Ser Val Met Gly Met Ile Gly Ile Leu
450 455 460
Pro Asp Met Thr Pro Ser Thr Glu Met Ser Leu Arg Gly Ile Arg Val
465 470 475 480
Ser Lys Met Gly Val Asp Glu Tyr Ser Ser Thr Glu Arg Val Val Val
485 490 495
Ser Ile Asp Arg Phe Leu Arg Val Arg Asp Gln Arg Gly Asn Val Leu
500 505 510
Leu Ser Pro Glu Glu Val Ser Glu Thr Gln Gly Thr Glu Lys Leu Thr
515 520 525
Ile Thr Tyr Ser Ser Ser Met Met Trp Glu Ile Asn Gly Pro Glu Ser
530 535 540
Val Leu Val Asn Thr Tyr Gln Trp Ile Ile Arg Asn Trp Glu Ser Leu
545 550 555 560
Lys Ile Gln Trp Ser Gln Asp Pro Thr Met Leu Tyr Asn Lys Met Glu
565 570 575
Phe Glu Pro Phe Gln Ser Leu Val Pro Lys Ala Ile Arg Ser Arg Tyr
580 585 590
Ser Gly Phe Val Arg Thr Leu Phe Gln Gln Met Arg Asp Val Leu Gly
595 600 605
Thr Phe Asp Thr Val Gln Ile Ile Lys Leu Leu Pro Phe Ala Ala Ala
610 615 620
Pro Pro Glu Gln Ser Arg Met Gln Phe Ser Ser Leu Thr Val Asn Val
625 630 635 640
Arg Gly Ser Gly Leu Arg Ile Leu Val Arg Gly Asn Ser Pro Val Phe
645 650 655
Asn Tyr Asn Lys Ala Thr Lys Arg Leu Thr Ile Leu Gly Lys Asp Ala
660 665 670
Gly Ala Leu Thr Glu Asp Pro Asp Glu Gly Thr Ala Gly Val Glu Ser
675 680 685
Ala Val Leu Arg Gly Phe Leu Ile Leu Gly Lys Glu Asp Lys Arg Tyr
690 695 700
Gly Pro Ala Leu Ser Ile Asn Glu Leu Ser Asn Leu Ala Lys Gly Glu
705 710 715 720
Lys Ala Asn Val Leu Ile Gly Gln Gly Asp Val Val Leu Val Met Lys
725 730 735
Arg Lys Arg Asp Ser Ser Ile Leu Thr Asp Ser Gln Thr Ala Thr Lys
740 745 750
Arg Ile Arg Met Ala Ile Asn
755
<210> 78
<211> 2341
<212> DNA
<213> 猪流感病毒
<400> 78
agcgaaagca ggtcaaatat attcaatatg gagagaataa aagaactaag agatctgatg 60
tcgcagtctc gcactcgcga gatactcaca aagaccactg tggaccatat ggccataatc 120
aaaaagtaca catcaggaag gcaagagaag aaccccgcac tcagaatgaa gtggatgatg 180
gcaatgaaat acccaattac agcagacaag agaataatgg acatgattcc agagaggaat 240
gaacaaggac aaaccctctg gagcaaaaca aacgatgctg gatcggaccg tgtgatggta 300
tcacccctgg ccgtaacatg gtggaatagg aatggcccaa caacaagcac agttcactac 360
cctaaggtat ataaaactta tttcgaaaag atcgaaaggt taaaacatgg tatctttggc 420
cctgtccact tcagaaatca agttaaaata agaaggaggg ttgacacaaa ccctggtcat 480
gcagatctca gtgccaagga ggcacaggat gtgatcatgg aagttgtttt cccaaatgaa 540
gtgggggcaa gagtactgac gtcagagtca cagctgacaa taacaaagga aaagaaagaa 600
gagctccagg attgtaagat tgctcccctg atggtggcat acatgctaga aagagagttg 660
gttcgcaaga cgaggtttct cccggtggct ggtggaacaa gcagtgttta tattgaagtg 720
ctacacttaa ctcagggaac atgctgggaa caaatgtaca ctccaggagg agaagtgaga 780
aatgatgatg ttgaccaaag tttgattatc gctgctagaa acatagtaag aagagcagca 840
gtgtcagcag acccattagc atctctcttg gaaatgtgcc acagcacaca gattggagga 900
ataaggatgg tggacatcct tagacagaac ccaacggagg aacaagccgt agacatatgc 960
aaggcagcaa tggggctgag gattagctct tctttcagct ttggtgggtt caccttcaaa 1020
agaacaagcg gatcatcagt taagaaagaa gaagaagtgc tcacgggcaa cctccaaaca 1080
ctgaaaataa gagtacatga aggatatgaa gaattcacaa tggtagggag aagagcaact 1140
gctattctca gaaaagcaac caggagattg atccagttaa tagtaagtgg gagagacgat 1200
caatcaattg ctgaggcaat aattgtagcc atggtatttt cacaagagga ttgcatgatc 1260
aaggcagtta ggggcgatct gaactttgtc aatagggcaa accagcgact gaatcccatg 1320
caccaactct tgaggcattt ccaaaaagat gcaaaagtgc ttttccagaa ctggggaatt 1380
gaacccatcg acagtgtgat gggaatgatc gggatattgc ctgatatgac cccaagcacg 1440
gaaatgtcgc tgagaggtat aagagtcagc aaaatgggag tagatgagta ttccagcacg 1500
gagagagtgg tagtgagcat tgaccgattt ttgagagttc gggatcaacg agggaacgta 1560
ctattgtccc ccgaagaggt cagcgagaca caaggaactg agaaattgac aataacttat 1620
tcgtcatcaa tgatgtggga gatcaatggt cctgagtcag tgctggtcaa cacttatcaa 1680
tggatcataa ggaattggga aagcttgaaa attcaatggt cacaagatcc cacgatgtta 1740
tacaacaaaa tggaatttga accattccag tctcttgtcc ctaaggcaac cagaagtcgt 1800
tacagtggat tcgtgaggac actgttccag caaatgcggg atgtgcttgg aacatttgac 1860
actgtccaaa taataaaact tctccccttt gctgctgctc caccggaaca gagtaggata 1920
cagttctcct cgctgactgt gaatgtgaga ggatcagggc tgaggatact ggtaagaggc 1980
aattctccag tgttcaatta caacaaagca accaaaaggc ttacaattct tggaaaagat 2040
gcaggtgcat tgactgaaga tccagatgaa ggcacagctg gagtggagtc tgctgtcctg 2100
aggggattcc tcattttggg taaagaagac aagagatatg gcccagcatt aagcatcaat 2160
gaactgagca atcttgcaaa aggagagaag gctaatgtgt taattgggca aggagacgtg 2220
gtgttggtaa tgaaacggaa acggaactct agcatactta ctgacagcca gacagcgacc 2280
aaaagaattc ggatggccat caattagtgt cgaattgttt aaaaacgacc ttgtttctac 2340
t 2341
<210> 79
<211> 2341
<212> DNA
<213> 猪流感病毒
<400> 79
agcgaaagca ggcaaaccat ttgaatggat gtcaacccga ctctactttt cctaaaggtt 60
ccagcgcaaa atgccataag caccacattc ccttatactg gagatcctcc atacagccat 120
ggaacaggaa caggatacac catggacaca gtcaacagaa cacaccagta ttcagaaaaa 180
gggaaatgga cgacaaacac agagactggg gcaccccagc tcaacccgat tgatggacca 240
ctacccgatg ataatgaacc aagtgggtat gcacaaacag actgtgtcct ggaggccatg 300
gctttccttg aagaatccca cccagggata tttgagaatt catgccttga aacaatggaa 360
attgtccaac aaacaagggt ggataaacta actcaaggtc gccagactta tgattggaca 420
ttaaacagaa atcaaccggc agcaactgca ttggccaaca ccatagaagt ttttagatca 480
aacggtctaa cagctaatga gtcaggaagg ctaatagatt tcctaaagga tgtaatggaa 540
tcaatggata aggaggaaat agagataaca acacattttc aaagaaaaag gagagtaaga 600
gacaacatga ccaagaagat ggtcacacaa agaacaatag ggaagaaaaa acaaaaattg 660
aataagagaa gttatctaat aagagcactg acattgaata cgatgaccaa agatgcagag 720
agaggcaagt taaaaaggag ggctatcgca acacctggga tgcagattag agggttcgtg 780
tactttgttg agactttagc tagaagcatc tgcgaaaagc ttgaacagtc cggactccca 840
gtagggggca atgaaaagaa agccaaattg gcaaatgttg tgagaaagat gatgactaat 900
tcacaagaca cagagctttc tttcacaatc actggagata acactaaatg gaatgaaaac 960
cagaatcctc gaatgttcct ggcgatgatc acatacatta ccagaaatca acccgagtgg 1020
ttcagaaaca tactgagtat ggcaccaata atgttctcaa acaaaatggc aagactagga 1080
aaagggtaca tgttcgagag taaaagaatg aagctccgaa cacaggtacc agcagaaatg 1140
ctagcaagca ttgatcttaa gtatttcaat gaatcaacaa ggaagaaaat tgagaaaata 1200
aggcctctcc taatagatgg cacagcatca ttgagccctg ggatgatgat gggcatgttc 1260
aacatgctaa gtacggtttt gggagtctca atactgaatc ttggacaaaa gaaatacacc 1320
aggacaacat actggtggga tggactccaa tcctcagacg attttgccct catagtaaat 1380
gcaccaaatc atgagggaat acaagcagga gtggatagat tctacaggac ctgcaagtta 1440
gtagggatca acatgagcaa aaagaagtcc tatataaata agactgggac atttgaattc 1500
acaagctttt tttatcgcta tgggtttgta gctaatttta gcatggagct gcccagtttt 1560
ggagtgtctg gaataaacga atcagctgat atgagcatcg gagtaacagt gataaagaac 1620
aacatgataa ataatgatct tggacctgca acagcccaga tggccctcca gttgttcatc 1680
aaagactaca gatacacata tagatgccat agaggggaca cacaaatcca gacgagaaga 1740
tcattcgagc taaagagcct gtggaatcaa actcaatcaa aggcaggatt attagtatct 1800
gatggaggac caaatttata caatatccgg aatcttcaca ttcctgaagt ctgcttaaaa 1860
tgggagctaa tggatgagga ttatcgggga agactttgta atcccctgaa tccctttgtc 1920
agccataaag agattgattc tgtaaacagt gctgtggtga tgccagccca tggtccagcc 1980
aaaagtatgg agtatgatgc cgttgcaact acacactcct ggattcccaa gaggaaccgc 2040
tctattctca acacaagcca aaggggaatt cttgaggatg aacagatgta ccagaagtgc 2100
tgcaacctgt tcgagaaatt tttccctagt agttcataca gaagaccagt tggaatttct 2160
agcatggtgg aggccatggt gtctagggcc cggattgatg ccaggattga cttcgagtct 2220
ggacggatta agaaagaaga gttctctgag atcatgaaga tctgttccac cattgaagaa 2280
ctcagacggc aaaagtaatg aatttagctt gtccttcatg aaaaaatgcc ttgtttctac 2340
t 2341
<210> 80
<211> 2233
<212> DNA
<213> 猪流感病毒
<400> 80
agcgaaagca ggtactgatc caaaatggaa gactttgtgc gacaatgctt caatccaatg 60
atcgtcgagc ttgcggaaaa ggcaatgaaa gaatatggag aagatccgaa aattgaaact 120
aacaaattcg ctgcaatatg cacacacttg gaagtatgtt tcatgtattc agatttccat 180
ttcattgacg agcggggtga atcaatcatt gtagaatctg gtgatccaaa tgcattactg 240
aagcaccgat ttgagataat tgaaggacgg gaccggacca tggcctggac agtagtgaac 300
agtatctgca acaccacagg ggtagagaag cctaaatttc ttccggattt atacgactac 360
aaagaaaatc ggttcattga aattggagtg acacgaaggg aggtccacat atactaccta 420
gagaaagcca acaaaataaa atccgagaag acacacattc acattttttc attcactgga 480
gaggagatgg ccaccaaagc agactacacc cttgatgaag aaagcagggc aagaatcaaa 540
accaggcttt tcaccataag acaagaaatg gcaagtaggg gtctatggga ttcctttcgt 600
cagtccgaaa gaggcgagga gacaattgaa gaaagatttg aaattacagg aaccatgcgc 660
agacttgccg accaaagtct cccaccgaac ttctccagtc ttgaaaactt tagagcttat 720
gtagatgggt tcgaaccaaa cggctgcatt gagggcaagc tttctcaaat gtcaaaagaa 780
gtgagcgccc aaattgaacc cttcttgaag acaacaccac gccctctaaa attgcctgat 840
gggcctcctt gctctcagcg gtcaaagttc ttgctgatgg atgctctgaa actaagtatt 900
gaagacccga gtcatgaagg agaaggaata ccactatatg atgcaatcaa gtgcatgaag 960
acattttttg gctggaaaga acccaacata atcaaaccac atgagaaagg cataaacccc 1020
aattacctac tggcttggaa gcaggtgcta gcagagctcc aagacattga aaatgaagag 1080
aagatcccaa agacaaagaa catgaggaga acaagccaat tgaagtgggc actcggtgag 1140
aatatggcac cagagaaagt agattttgat gactgcaaag atgttggtga tcttaaacag 1200
tatgacagcg acgagccaga gcccagatct ctagcaagtt gggtccaaaa tgaattcaac 1260
aaggcatgtg aattgaccga ttcaagctgg atagaacttg atgagatagg agaagatatt 1320
gcaccgattg aacacatcgc aagtatgagg aggaactatt ttacagcaga agtgtcccat 1380
tgtagggcta cggaatacat aatgaaggga gtgtacataa acacggcttt gcttaatgca 1440
tcttgtgcag ccatggatga ctttcagctg atcccaatga taagcaaatg caggaccaaa 1500
gaaggaagac gaaaaacaaa tctgtatggg ttcattataa aaggaaggtc ccatctgagg 1560
aatgatactg acgtggtgaa ctttgtaagc atggagttct ccctcaccga cccgagactg 1620
gagccacaca aatgggaaaa atactgtgtt cttgaaatag gagacatgct cctgaggact 1680
gcgataggcc aagtgtcgag gcccatgttc ttatatgtga gaaccaatgg aacctccaag 1740
atcaagatga aatggggcat ggaaatgagg cgctgccttc ttcaatctct tcagcagatt 1800
gagagcatga ttgaggctga gtcttctgta aaagagaaag acatgaccaa ggaatttttt 1860
gaaaacaaat cggaaacatg gccaattgga gaatcaccca aaggagtgga ggaaggctct 1920
attgggaaag tgtgcaggac cttactggca aaatctgtat tcaacagtct atacgcatct 1980
ccacaacttg agggattttc ggctgaatcg agaaagttgc ttctcattgt tcaggcactt 2040
agggacaacc tggaacctgg aaccttcgat cttggggggc tatatgaagc aatcgaggag 2100
tgcctgatta atgatccctg ggttttgctt aatgcatctt ggttcaactc cttcctcaca 2160
catgcactga aatagttgtg gcaatgctac tatttgctat ccatactgtc caaaaaagta 2220
ccttgtttct act 2233
<210> 81
<211> 1565
<212> DNA
<213> 猪流感病毒
<400> 81
agcaaaagca gggtagataa tcactcaatg agtgacatcg aagccatggc atctcaaggc 60
accaaacgat catatgaaca aatggagact ggtggtgaac gccaggatgc cacagaaatc 120
agagcatctg tcggaagaat gattggtgga atcgggaaat tctacatcca aatgtgcact 180
gaactcaaac tcagtgacta tgagggacga ctaatccaaa atagcataac aatagagaga 240
atggtgctct ctgcttttga tgagagaaga aataaatacc tagaagagca tcccagtgct 300
gggaaagacc ctaagaaaac tggaggaccc atatatagaa gagtagacgg aaagtggatg 360
agagaactca ttctttatga caaagaagaa ataaggagag tttggcgcca ggcaaacaat 420
ggtgatgatg caacagctgg tcttactcat atcatgattt ggcattccaa tctgaatgat 480
gccacgtacc agagaacaag agcacttgtt cgcaccggaa tggatcccag aatgtgctct 540
ctaatgcaag gttcaacact tcccagaagg tctggagcag caggtgctgc agtgaaagga 600
gttggaacaa taacaatgga attaatcaga atgatcaaac gggggatcaa tgaccgaaat 660
ttctggagag gtgaaaatgg aagaaggaca aggattgcat atgaaagaat gtgcaatatt 720
ctcaaaggaa aatttcagac agctgcccaa agggcaatga tggatcaagt gagagaaagt 780
cggaacccag ggaacgctga gattgaagat ctcattttcc tggcacggtc agcacttatc 840
ctaaggggat cagttgcaca taagtcttgc ctgcctgctt gcgtgtatgg gcttgcagtg 900
gcaagtgggc atgactttga aagggaaggg tattcgctgg tcgggataga cccatttaaa 960
ttactccaga acagtcaagt gttcagcctg gtaagaccaa atgaaaaccc agctcacaag 1020
agtcaattag tgtggatggc atgccactct gctgcatttg aggatctaag ggtctcaagt 1080
ttcataagag ggaagaaagt gattccaagg ggaaagcttt ccacaagagg ggttcagatt 1140
gcttcaaatg agaatgtgga agccatggat tccaatacct tagagctgag aagcagatac 1200
tgggctataa ggaccagaag tggaggaaat actaatcaac agaaagcatc cgcaggccag 1260
atcagtgtgc aacctacatt ctcagtgcaa cggaatctcc cttttgaaag agcaaccgtt 1320
atggcagctt tcagcggaaa caatgaagga cggacatccg atatgcggac agaaattata 1380
aggatgatgg aaaatgcaaa accagaagat ttgtccttcc aggggcgggg agtcttcgag 1440
ctctcggacg aaaaggcaac gagcccgatc gtgccttcct ttgacatgag taatgaaggg 1500
tcttatttct tcggagacaa tgcagaggag tatgacagtt gatgaaaaat acccttgttt 1560
ctact 1565
<210> 82
<211> 1027
<212> DNA
<213> 猪流感病毒
<400> 82
agcaaaagca ggtagatgtt taaagatgag tcttctaacc gaggtcgaaa cgtatgttct 60
ctctatcgtc ccgtcaggcc ccctcaaagc cgagatagca cagaggctcg aagacgtttt 120
tgcagggaaa aacaccgatc ttgaggctct catggaatgg ctaaagacaa gaccaatcct 180
gtcacctctg actaaaggga ttttagggtt tgtgttcacg ctcaccgtgc ccagtgagcg 240
aggactgcag cgtagacgtt ttgtccagaa tgccctcaat gggaatggtg acccaaacaa 300
catggacaag gcggtaaaac tgtacaggaa actaaaaagg gaaataacat tccatggggc 360
caaggaagta gcgctcagtt actctgctgg tgcacttgcc agttgcatgg gcctcatata 420
caacagaatg gggactgtcg ccactgaggt ggcatttggt ctggtatgcg caacctgtga 480
acaaattgct gattctcagc atcgatctca tagacaaatg gtgacaacaa ccaatccact 540
aatcaggcac gagaacagaa tggtaatagc cagcacaaca gctaaggcca tggaacaaat 600
ggctggatca agtgaacaag cagcagaggc tatggaggtt gccagtcagg ctagacaaat 660
ggtacaggca atgagaacaa ttgggactca ccctagttcc agcactggtc taaaagatga 720
tcttcttgaa aatttacagg cctatcagaa acggatggga gtgcaaatgc aacgattcaa 780
gtgatcctct cattgatgcc gcaagcatca ttggtatttt gcacctgata ttgtggattc 840
ttgatcgtct ttttttcaaa tgcatctacc gtcgctttaa atacggtctg caaagagggc 900
cttctacgga aggagtgccg gagtccatga gggaagaata tcggcagaaa cagcagagtg 960
ctgtggatgt tgacgatggt cattttgtca acatagtgct agagtaaaaa actaccttgt 1020
ttctact 1027
<210> 83
<211> 890
<212> DNA
<213> 猪流感病毒
<400> 83
agcaaaagca gggtgacaaa gacataatgg actccaatac tgtgtcaagc tttcaggtag 60
actgtttcct ttggcacatc cgcaaacgat ttgcagacaa tggattgggt gatgccccat 120
tccttgatcg gctccgccga gatcaaaagt ccctaaaagg aaggggcaac acccttagcc 180
tagacatcga aacagccact cttgttggga aacaaattgt tgagtggatt ttgaaagagg 240
aatccagcga tatacttaag atgaccattg catctgtgcc tacttcgcgc tacctagctg 300
acatgaccct cgaggaaatg tcacgagact ggttcatgct aatgcctagg caaaagataa 360
taggccctct ttgtgtgcga gtggaccagg cgatcatgga aaagaacatc atactgaaag 420
cgaacttcag tgtgatcttt aaccgattag agactttgat actactaagg gctttcactg 480
aggagggagc aatcgttgga gaaatttcac cattacctta tcttccagga catactaatg 540
aggatgtcaa aaatgcagtt ggggtcctca tcggagggct tgaatggaat ggtaacacgg 600
ttcgaggctc tgaaaatcta cagagattcg cttggagaaa ccataatgag gatgggagat 660
cttcactacc tccagaacag aaatgaaaag tggcgagagc aattgggaca gaaatttgag 720
gaaataagat ggttaattga agaaatacgg cacagattga aagcgacaga aaatagtttc 780
gagcaaataa catttatgca agccttacaa ctactgcttg aagtagaaca agagataagg 840
actttctcgt ttcagcttat ttaatgataa aaaacaccct tgtttctact 890
<210> 84
<211> 1778
<212> DNA
<213> 猪流感病毒
<400> 84
agcaaaagca ggggaaaata aaagcaacca aaatgaaggc aatactagta gttctgctat 60
atacatttgc aacctcaaat gcagacacat tatgtatagg ttatcatgcg aacaattcaa 120
cagacactgt agacacagta ctagaaaaga atgtaacagt aacacactct gttaaccttc 180
tagaagacaa gcataacggg aaactatgca aactaagagg ggtagcccca ttgcatttgg 240
gtaaatgtaa cattgctggc tggatcctgg gaaatccaga gtgtgaatca ctctccacag 300
caagctcatg gtcctacatt gtggaaacat ctagttcagg caatggaacg tgttacccag 360
gagatttcat cgattatgag gagctaagag agcaattgag ctcagtgtca tcatttgaaa 420
ggtttgagat attccccaag acaagttcat ggcccaatca tgaatcgaac aaaggtgtaa 480
cggcagcatg tcctcatgct ggagaaaaaa gcttctacaa aaatttaata tggctagtta 540
aaaaaggaaa ctcataccca aagctcagca aatcctacat taatgataaa gggaaagaag 600
tcctcgtgct atggggcatt caccatccat ctactagtgc tgaccaacaa agtctctatc 660
agaatgcaga tgcatatgtt tttgtgggga catcaagata cagcaagaag ttcaagccgg 720
aaatagcaat aagacccaaa gtgagggatc aagaagggag aatgaactat tactggacac 780
tagtagagcc gggagacaaa ataacattcg aagcaactgg aaatctagtg gtaccgagat 840
atgcattcgc aatggaaaga aatgctggat ctggtattat catttcagat acaccagtcc 900
acgattgcaa tacaacttgt cagacaccca agggtgctat aaacaccagc cttccttttc 960
agaatataca tccgatcaca attggaaaat gtccaaaata tgtaaaaagc acaaaattga 1020
gactggccac aggattgagg aatgtcccgt ctattcaatc tagaggccta tttggggcca 1080
ttgccggttt cattgaaggg gggtggacag ggatggtaga tggatggtac ggttatcacc 1140
atcaaaatga gcaggggtca ggatatgcag ccgacctgaa gagcacacag aatgccattg 1200
acgagattac taacaaagta aattctgtta ttgaaaagat gaatacacag ttcacagcag 1260
taggtaaaga gttcaaccac ctggaaaaaa gaatagagaa tttaaataaa aaagttgatg 1320
atggtttcct ggacatttgg acttacaatg ccgaactgtt ggttctattg gaaaatgaaa 1380
gaactttgga ctaccacgat tcaaatgtga agaacttata tgaaaaggta agaagccagt 1440
taaaaaacaa tgccaaggaa attggaaacg gctgctttga attttaccac aaatgcgata 1500
acacgtgcat ggaaagtgtc aaaaatggga cttatgacta cccaaaatac tcagaggaag 1560
caaaattaaa cagagaagaa atagatgggg taaagctgga atcaacaagg atttaccaga 1620
ttttggcgat ctattcaact gtcgccagtt cattggtact ggtagtctcc ctgggggcaa 1680
tcagtttctg gatgtgctct aatgggtctc tacagtgtag aatatgtatt taacattagg 1740
atttcagaaa catgagaaaa aacacccttg tttctact 1778
<210> 85
<211> 1458
<212> DNA
<213> 猪流感病毒
<400> 85
agcaaaagca ggagtttaaa atgaatccaa accaaaagat aataaccatt ggttcggtct 60
gtatgacaat tggaatggct aacttaatat tacaaattgg aaacataatc tcaatatgga 120
ttagccactc aattcaactt gggaatcaaa atcagattga aacatgcaat caaagcgtca 180
ttacttatga aaacaacact tgggtaaatc agacatatgt taacatcagc aacaccaact 240
ttgctgctgg acagtcagtg gtttccgtga aattagcggg caattcctct ctctgccctg 300
ttagtggatg ggctatatac agtaaagaca acagtgtaag aatcggttcc aagggggatg 360
tgtttgtcat aagggaacca ttcatatcat gctccccctt ggaatgcaga accttcttct 420
tgactcaagg ggccttgcta aatgacaaac attccaatgg aaccattaaa gacaggagcc 480
catatcgaac cctaatgagc tgtcctattg gtgaagttcc ctctccatac aactcaagat 540
ttgagtcagt cgcttggtca gcaagtgctt gtcatgatgg catcaattgg ctaacaattg 600
gaatttctgg cccagacaat ggggcagtgg ctgtgttaaa gtacaacggc ataataacag 660
acactatcaa gagttggaga aacaatatat tgagaacaca agagtctgaa tgtgcatgtg 720
taaatggttc ttgctttact gtaatgaccg atggaccaag taatggacag gcctcataca 780
agatcttcag aatagaaaag ggaaagatag tcaaatcagt cgaaatgaat gcccctaatt 840
atcactatga ggaatgctcc tgttatcctg attctagtga aatcacatgt gtgtgcaggg 900
ataactggca tggctcgaat cgaccgtggg tgtctttcaa ccagaatctg gaatatcaga 960
taggatacat atgcagtggg attttcggag acaatccacg ccctaatgat aagacaggca 1020
gttgtggtcc agtatcgtct aatggagcaa atggagtaaa agggttttca ttcaaatacg 1080
gcaatggtgt ttggataggg agaactaaaa gcattagttc aagaaacggt tttgagatga 1140
tttgggatcc gaacggatgg actgggacag acaataactt ctcaataaag caagatatcg 1200
taggaataaa tgagtggtca ggatatagcg ggagttttgt tcagcatcca gaactaacag 1260
ggctggattg tataagacct tgcttctggg ttgaactaat cagagggcga cccaaagaga 1320
acacaatctg gactagcggg agcagcatat ccttttgtgg tgtaaacagt gacactgtgg 1380
gttggtcttg gccagacggt gctgagttgc catttaccat tgacaagtaa tttgttcaaa 1440
aaactccttg tttctact 1458
<210> 86
<211> 1776
<212> DNA
<213> 猪流感病毒
<400> 86
agcaaaagca ggggaaaaat aaaagcaacc aaaatgaaag taaaactaat ggttctgtta 60
tgtacattta cagctacata tgcagacaca atatgtgtag gctaccatgc caacaactca 120
actgacactg ttgacacagt acttgagaag aatgtgacag tgacacactc tgtcaaccta 180
cttgaggaca gccacaatgg aaaactatgt ctactaaaag gaatagctcc actacaattg 240
ggtagttgca gcgttgccgg atggatctta ggaaacccag agtgcgaatt gctgatttcc 300
aaggaatctt ggtcctacat tgtagaaaca ccaaatcctg agaatggaac atgttaccca 360
gggtatttca cagactatga agaactgagg gagcaattga gttcagtatc ttcatttaag 420
aggttcgaaa tattccccaa agagagctca tggcccaacc acaccgtaac cggagtgtca 480
tcatcatgct cccataacgg gaaaagcagc ttctacagaa atttgctatg gctgacggtg 540
aagaacggtc tgtacccaaa cctgagcaag tcctatacaa acaaaaagga gaaagaagtc 600
cttgtactat ggggtgttca tcacccatct aacatagggg accaaagggc cctctatcat 660
acagaaaatg cttatgtctc tgtagtgtct tcacattata gcagaagatt caccccagaa 720
atagccaaaa gacccaaggt gagaaatcag gaaggaagaa tcaactacta ctggaccctg 780
ctagaacccg gggatacaat aatatttgag gcaaatggaa atctaatagc accaaggtat 840
gccttcgaac tgagtaaggg ttttggatca ggaatcatca catcaaatgc accaatgggt 900
gaatgtaatg caaagtgtca aacacctcag ggagctataa acagcagtct tcctttccag 960
aatgtacacc cagtaacaat aggagagtgc ccaaagtatg tcaaaagtgc aaaattaagg 1020
atggttacag gactaaggaa caccccatcc attcaatcca gaggtttgtt tggagccatt 1080
gccggtttca ttgaaggagg gtggactgga atggtagatg gttggtatgg ttatcaccat 1140
cagaatgagc aaggatctgg gtatgctgca gaccaacaaa gcacacaaaa tgccattaat 1200
gggattacaa acaaggtgaa ttctgtgatt gaaaaaatga acactcaatt cacagctgtg 1260
ggcaaagaat tcaacaaact ggaaagaaga atggaaaact taaataaaaa ggttgatgat 1320
gggtttctag acatttggac atataatgca gaattgttag ttctactgga aaatgaaagg 1380
actttggatt tccatgactc caacgtgaag aatctgtatg agaaagtaaa aagccaatta 1440
aaaaataatg ccaaagaaat aggaaacggg tgttttgaat tctatcataa gtgtaacgat 1500
gaatgcatgg agagtgtgaa aaatggaact tatgactatc caaaatattc cgaagaatca 1560
aagttaaaca gggagaaaat tgatggagtg aaattggaat caatgggagt ctataatatc 1620
ctggcgatct actcaacagt cgccagttcc ctagttcttt tagtctccct gggggcaatc 1680
agcttctgga tgtgttccaa tgggtcttta cagtgtagaa tatgcatcta agaccagaat 1740
ttcagaaata taaggaaaaa cacccttgtt tctact 1776
<210> 87
<211> 1458
<212> DNA
<213> 猪流感病毒
<400> 87
agcaaaagca ggagtttaaa atgaatccaa atcaaaagat aataacgatt ggctctgttt 60
ctcttactat tgccacaatg tgcttcctta tgcaaattgc catcctggta actaatgtaa 120
cattgcactt caatcaatat gaatgcaact accccccaaa caaccaagta atactgtgtg 180
aaccaacaat aatagaaaga aacataacag agatagtgta tctgaccaac accaccatag 240
agaaggaaat atgccccaaa ctagcagaat acagaaattg gtcaaagccg caatgtaaaa 300
ttacagggtt tgcacctttt tccaaggaca attcgattag gctttctgct ggtggggaca 360
tttgggtgac gagagaacct tatgtgtcat gcgatcctga taagtgttat cagtttgccc 420
ttggacaagg aacaacatta aacaacaggc attcaaatga cacagtacat gataggaccc 480
cttatcgaac cctattgatg aatgagttgg gtattccatt ccatttgggg accaaacaag 540
tgtgcatagc atggtccagc tcaagttgtc atgatggaaa agcatggctt cacgtttgta 600
ttactgggca tgatgaaaat gcaactgcca gcatcattta caatggaaga cttgtagata 660
gtattggttc atggtccaaa aaaatactca ggacacagga gtcggaatgt gtttgcatca 720
atggaacttg tacagtagta atgactgatg ggagtgcttc aggaatagct gacactaaaa 780
tattattcat tgaagagggg aaaatcgttc atattagccc attgttagga agtgctcagc 840
atgtagagga gtgctcctgt tatccccgat atcctggtgt cagatgcatc tgtagagaca 900
actggaaagg ttccaataga cccgtcgtag atataaatgt aaaggattat agcattgttt 960
ccagttatgt gtgctcagga cttgttggag atacacccag aaaagacgac agatccagca 1020
gtagcgattg tctgaatcct aacaatgagg aaggggggca tggagtgaaa ggctgggcct 1080
ttgatgatgg aaatgatgtg tggatgggaa gaacaatcaa cgagacgtta cgctcaggtt 1140
atgaaacctt caaagtcatt gaaggctggt ccaaacctaa ttccaaattg cagataaata 1200
ggcaagtcat agttgaaaga ggtgataggt ccggttattc tggcattttc tctgttgaag 1260
gcaaaagctg tatcaatcgg tgcttttatg tggagttgat aagaggaagg aaacaggaaa 1320
ctgcagtatg gtggacgtca aacagtattg ttgtgttttg tggcacctca ggtacatatg 1380
gaacaggctc atggcctgat ggggcgaaca tcaatctcat gcctgtataa tttattcaaa 1440
aaactccttg tttctact 1458
<210> 88
<211> 1762
<212> DNA
<213> 猪流感病毒
<400> 88
agcaaaagca ggggatattt ctattaacca tgaagactat cattgctttt agctgcgttt 60
tatgtttgat tttcgctcaa aaacttcccg gaagtgacaa cagcatggca acgctgtgcc 120
tgggacacca tgcagtacca aacggaacgt tagtgaaaac aatcacggat gaccaaattg 180
aagtgactaa tgctactgag ctggttcaga gttcctcaac aggtagaata tgcaacagtc 240
ctcaccaaat ccttgatggg aaaaattgca cactgataga tgctctattg ggagaccctc 300
attgtgatga cttccaaaac aaggaatggg acctttttgt tgaacgaagc acagcctaca 360
gcaactgtta cccttattat gtgccggatt atgcctccct taggtcacta gttgcatcat 420
ccggcaccct ggaatttacc caagaaagct tcaattggac tggagttgct caagatggat 480
caagctatgc ttgcagaagg gaatctgtta acagtttctt tagtagattg aattggttgc 540
ataaattgga ttacaaatat ccagcgctga aagtaactat gccgaacaat gacaaattcg 600
acaaattgta catttggggg gttcaccacc cgggcactga cagggaccaa accaacctat 660
atgttcaaac atcagggaga gttacagtct ccaccaaaag aagccaacaa actgtaatcc 720
caaatatcgg gtctagaccc tgggtaaggg gtgtctccag cataataagc atctattgga 780
caatagtaaa accgggagac atacttttga ttaacagcac agggaatcta attgcccctc 840
ggggttactt caaattacaa agtgggaaaa gctcaataat gagatcagat gcacccattg 900
gcatctgcaa ttctgaatgc attactccaa atggaagcat tcccaacgac aaaccttttc 960
aaaatgtaaa caggatcact tatggggcct gtcccagata tgttaagcaa aacaccctga 1020
aattggcaac aggaatgcgg aatgtaccag agaaacaaac cagaggcata tttggcgcaa 1080
tcgcaggttt catagaaaat ggttgggaag ggatggtgga cggttggtac ggtttcaggc 1140
atcaaaattc tgaaggcaca ggacaagcag cagatcttaa aagcactcgt gcagcaatca 1200
accaaatcac cgggaaacta aatagagtaa tcaagaaaac gaacgagaaa ttccatcaga 1260
tcgaaaaaga attctcagaa gtagaaggga gaattcagga cctagagaaa tacgttgaag 1320
acactaaaat agacctctgg tcttacaacg cggagcttct tgttgccctg gagaaccaac 1380
acacaattga tttaactgac tcagaaatga acaaactgtt cgaaagaaca agaaagcaat 1440
tgcgggaaaa tgctgaggac atgggcaatg gttgcttcaa aatataccac aaatgtgaca 1500
atgcctgcat aggatcaatc agaaatggaa cttatgacca tgatgtatac agagatgagg 1560
cattaaacaa tcggttccag atcaaaggtg ttcagctgaa gtcaggatac aaagattgga 1620
tcctatggat ttcctttgcc atatcatgct ttttgctttg tgttgttctg ctggggttca 1680
ttatgtgggc ctgccaaaaa ggcaacatta ggtgcaacat ttgcatttga gtgcattaat 1740
taaaaacacc cttgtttcta ct 1762
<210> 89
<211> 1465
<212> DNA
<213> 猪流感病毒
<400> 89
agcaaaagca ggagtaaaga tgaatccaaa tcaaaagata ataacaattg gctctgtttc 60
tctcctcatt gccacaatat gcttccttat gcaaattgcc atcctggtaa ctactgtaac 120
attgcatttc aagcagcatg attgcaactc ctccccaaac aaccaagtaa tgctgtgtga 180
accaacaata atagaaagaa acacaacaga gattgtgtat ctgaccaaca taactataga 240
gaaggaaata tgccccaaac tagcagaata cagaaattgg tcaaagcctc aatgtaacat 300
tacaggattt gcacctttct ctaaggacaa ttcgattcgg ctttccgctg gcggggacat 360
ctgggtgaca agagaacctt atgtgtcgtg cgatcctgac aagtgttatc aatttgccct 420
tgggcaggga acaacactaa acaacggtca ttcaaatgac actgtacatg ataggacccc 480
ttaccgaacc ctattgatga atgaattggg tgttccattt catttgggga ccaggcaagt 540
gtgcatagca tggtccagct caagttgtca cgatggaaaa gcatggttgc atgtttgtat 600
aactggggat gataaaaatg caactgctag cttcatttac aatgggaggc ttgtagatag 660
tattggttca tggtccaaaa atatactcag aacccaggag tcggaatgcg tttgtatcaa 720
tggaacttgt acagtagtaa tgactgatgg gagcgcttca ggaaaagctg atactaaagt 780
actattcatt gaggagggaa aaatcgttca tattagcaca ttgtcaggaa gtgctcagca 840
tgtcgaggag tgctcctgtt atcctcgata tcctggtgtc agatgtgtct gtagagacaa 900
ctggaaaggc tccaacaggc ccatcgtaga cataaatgta aaggattata gtattgtttc 960
cagttatgta tgctcaggac ttgttggaga cacacccaga aaaaacgaca gattcagcag 1020
tagccattgc caagatccta acaatgagga aggaggtcat ggggtgaaag gctgggcctt 1080
tgatgatgga aatgacgtgt ggatgggaag aacgatcaac gagaaattac gctcaggtta 1140
tgaaaccttc aaagtcatcg aaggctggtc caaacctaac tccaaattac agacaaatag 1200
gcaagtcata gttgaaagag gtaacaggtc cggttattct ggtattttct ccgttgaagg 1260
caaaagctgc atcaatcggt gtttttatgt ggagttgata aggggaagga aagaggaaac 1320
taaagtctgg tggacctcaa acagtattgt tgtgctttgt ggcacctcag gtacatatgg 1380
aacaggctca tggcctgatg gggcggatat caatctcatg cctatataac tttcgcaatt 1440
ttagaaaaaa ctccttgttt ctact 1465
<210> 90
<211> 709
<212> DNA
<213> 人工序列
<220>
<223> TRIG H1N1的NS-DO CDS + 5' 和 3'UTR
<400> 90
agcaaaagca gggtgacaaa gacataatgg actccaatac tgtgtcaagc tttcaggtag 60
actgtttcct ttggcacatc cgcaaacgat ttgcagacaa tggattgggt gatgccccat 120
tccttgatcg gctccgccga gatcaaaaat cgttaaaagg acgtggaaat acgttatcgt 180
tagatataga aacggcgacg ctagtcggaa aacaaatagt cgaatggata ttaaaagaag 240
aatcgtcgga tatattaaaa atgacgatag cgtcggtccc gacgtcgcgt tatttagcgg 300
atatgacgtt agaagaaatg tcgcgtgatt ggtttatgtt aatgccgcgt caaaaaataa 360
taggaccgtt atgtgtccgt gtcgatcaag cgataatgga aaaaaatata atattaaaag 420
cgaatttttc ggtcatattt aatcgtttag aaacgttaat attattacgt gcgtttacgg 480
aggagggagc aatcgttgga gaaatttcac cattacctta tcttccagga catactaatg 540
aggatgtcaa aaatgcagtt ggggtcctca tcggagggct tgaatggaat ggtaacacgg 600
ttcgaggctc tgaaaatcta cagagattcg cttggagaaa ccataatgag gatgggagat 660
cttcactacc tccagaacag aaatgataaa aaacaccctt gtttctact 709
<210> 91
<211> 1778
<212> DNA
<213> 人工序列
<220>
<223> H1N1的HA-DO CDS + 5' 和 3'UTR
<400> 91
agcaaaagca ggggaaaata aaagcaacca aaatgaaggc aatactagta gttctgctat 60
atacatttgc aacctcaaat gcagacacat tatgtatagg ttatcatgcg aacaattcaa 120
cagatacggt cgatacggtc ttagaaaaaa atgtcacggt cacgcattcg gtcaatttat 180
tagaagataa acataatgga aaattatgta aattacgtgg agtcgcgccg ttacatttag 240
gaaaatgtaa tatagcggga tggatattag gaaatccgga atgtgaatcg ttatcgacgg 300
cgtcgtcgtg gtcgtatata gtcgaaacgt cgtcgtcggg aaatggaacg tgttatccgg 360
gagattttat agattatgaa gaattacgtg aacaattatc gtcggtctcg tcgtttgaac 420
gttttgaaat atttccgaaa acgtcgtcgt ggccgaatca tgaatcgaat aaaggagtca 480
cggcggcgtg tccgcatgcg ggagaaaaat cgttttataa aaatttaata tggctagtca 540
aaaaaggaaa ttcgtatccg aaattatcga aatcgtatat aaatgataaa ggaaaagaag 600
tcttagtctt atggggaata catcatccgt cgacgtcggc ggatcaacaa tcgttatatc 660
aaaatgcgga tgcgtatgtc tttgtcggaa cgtcgcgtta ttcgaaaaaa tttaaaccgg 720
aaatagcgat acgtccgaaa gtccgtgatc aagaaggacg catgaattat tattggacgc 780
tagtcgaacc gggagataaa ataacgtttg aagcgacggg aaatttagtc gtcccgcgtt 840
atgcgtttgc gatggaacgt aatgcgggat cgggaataat aatatcggat acgccggtcc 900
atgattgtaa tacgacgtgt caaacgccga aaggagcgat aaatacgtcg ttaccgtttc 960
aaaatataca tccgataacg ataggaaaat gtccgaaata tgtcaaatcg acgaaattac 1020
gtttagcgac gggattacgt aatgtcccgt cgatacaatc gcgtggatta tttggagcga 1080
tagcgggatt tatagaagga ggatggacgg gaatggtcga tggatggtat ggatatcatc 1140
atcaaaatga acaaggatcg ggatatgcgg cggatttaaa atcgacgcaa aatgcgatag 1200
atgaaataac gaataaagtc aattcggtca tagaaaaaat gaatacgcaa tttacggcgg 1260
tcggaaaaga atttaatcat ttagaaaaac gtatagaaaa tttaaataaa aaagtcgatg 1320
atggattttt agatatatgg acgtataatg cggaattatt agtcttatta gaaaatgaac 1380
gtacgttaga ttatcatgat tcgaatgtca aaaatttata tgaaaaagtc cgttcgcaat 1440
taaaaaataa tgcgaaagaa ataggaaatg gatgttttga attttatcat aaatgtgata 1500
atacgtgtat ggaatcggtc aaaaatggaa cgtatgatta tccgaaatat tcggaagaag 1560
cgaaattaaa tcgtgaagaa atagatggag tcaaattaga atcgacgcgt atatatcaaa 1620
tattagcgat atattcgacg gtcgcgtcgt cattggtact ggtagtctcc ctgggggcaa 1680
tcagtttctg gatgtgctct aatgggtctc tacagtgtag aatatgtatt taacattagg 1740
atttcagaaa catgagaaaa aacacccttg tttctact 1778
<210> 92
<211> 1458
<212> DNA
<213> 人工序列
<220>
<223> H1N1的NA-DO CDS + 5' 和 3'UTR
<400> 92
agcaaaagca ggagtttaaa atgaatccaa accaaaagat aataaccatt ggttcggtct 60
gtatgacaat tggaatggct aacttaatat tacaaattgg aaacataatc tcaatatgga 120
tttcgcattc gatacaatta ggaaatcaaa atcaaataga aacgtgtaat caatcggtca 180
taacgtatga aaataatacg tgggtcaatc aaacgtatgt caatatatcg aatacgaatt 240
ttgcggcggg acaatcggtc gtatcggtca aattagcggg aaattcgtcg ttatgtccgg 300
tctcgggatg ggcgatatat tcgaaagata attcggtccg tataggatcg aaaggagatg 360
tctttgtcat acgtgaaccg tttatatcgt gttcgccgtt agaatgtcgt acgttttttt 420
taacgcaagg agcgttatta aatgataaac attcgaatgg aacgataaaa gatcgttcgc 480
cgtatcgtac gttaatgtcg tgtccgatag gagaagtccc gtcgccgtat aattcgcgtt 540
ttgaatcggt cgcgtggtcg gcgtcggcgt gtcatgatgg aataaattgg ttaacgatag 600
gaatatcggg accggataat ggagcggtcg cggtcttaaa atataatgga ataataacgg 660
atacgataaa atcgtggcgt aataatatat tacgtacgca agaatcggaa tgtgcgtgtg 720
tcaatggatc gtgttttacg gtcatgacgg atggaccgtc gaatggacaa gcgtcgtata 780
aaatatttcg tatagaaaaa ggaaaaatag tcaaatcggt cgaaatgaat gcgccgaatt 840
atcattatga agaatgttcg tgttatccgg attcgtcgga aataacgtgt gtctgtcgtg 900
ataattggca tggatcgaat cgtccgtggg tctcgtttaa tcaaaattta gaatatcaaa 960
taggatatat atgttcggga atatttggag ataatccgcg tccgaatgat aaaacgggat 1020
cgtgtggacc ggtctcgtcg aatggagcga atggagtcaa aggattttcg tttaaatatg 1080
gaaatggagt ctggatagga cgtacgaaat cgatatcgtc gcgtaatgga tttgaaatga 1140
tatgggatcc gaatggatgg acgggaacgg ataataattt ttcgataaaa caagatatag 1200
tcggaataaa tgaatggtcg ggatattcgg gatcgtttgt ccaacatccg gaattaacgg 1260
gattagattg tatacgtccg tgtttttggg tcgaattaat acgtggacgt ccgaaagaaa 1320
atacgatatg gactagcggg agcagcatat ccttttgtgg tgtaaacagt gacactgtgg 1380
gttggtcttg gccagacggt gctgagttgc catttaccat tgacaagtaa tttgttcaaa 1440
aaactccttg tttctact 1458
<210> 93
<211> 1776
<212> DNA
<213> 人工序列
<220>
<223> H1N2的HA-DO CDS + 5' 和 3'UTR
<400> 93
agcaaaagca ggggaaaaat aaaagcaacc aaaatgaaag taaaactaat ggttctgtta 60
tgtacattta cagctacata tgcagacaca atatgtgtag gctaccatgc caacaactca 120
actgatacgg tcgatacggt cttagaaaaa aatgtcacgg tcacgcattc ggtcaattta 180
ttagaagatt cgcataatgg aaaattatgt ttattaaaag gaatagcgcc gttacaatta 240
ggatcgtgtt cggtcgcggg atggatatta ggaaatccgg aatgtgaatt attaatatcg 300
aaagaatcgt ggtcgtatat agtcgaaacg ccgaatccgg aaaatggaac gtgttatccg 360
ggatatttta cggattatga agaattacgt gaacaattat cgtcggtctc gtcgtttaaa 420
cgttttgaaa tatttccgaa agaatcgtcg tggccgaatc atacggtcac gggagtctcg 480
tcgtcgtgtt cgcataatgg aaaatcgtcg ttttatcgta atttattatg gttaacggtc 540
aaaaatggat tatatccgaa tttatcgaaa tcgtatacga ataaaaaaga aaaagaagtc 600
ttagtcttat ggggagtcca tcatccgtcg aatataggag atcaacgtgc gttatatcat 660
acggaaaatg cgtatgtctc ggtcgtatcg tcgcattatt cgcgtcgttt tacgccggaa 720
atagcgaaac gtccgaaagt ccgtaatcaa gaaggacgta taaattatta ttggacgtta 780
ttagaaccgg gagatacgat aatatttgaa gcgaatggaa atttaatagc gccgcgttat 840
gcgtttgaat tatcgaaagg atttggatcg ggaataataa cgtcgaatgc gccgatggga 900
gaatgtaatg cgaaatgtca aacgccgcaa ggagcgataa attcgtcgtt accgtttcaa 960
aatgtccatc cggtcacgat aggagaatgt ccgaaatatg tcaaatcggc gaaattacgt 1020
atggtcacgg gattacgtaa tacgccgtcg atacaatcgc gtggattatt tggagcgata 1080
gcgggattta tagaaggagg atggacggga atggtcgatg gatggtatgg atatcatcat 1140
caaaatgaac aaggatcggg atatgcggcg gatcaacaat cgacgcaaaa tgcgataaat 1200
ggaataacga ataaagtcaa ttcggtcata gaaaaaatga atacgcaatt tacggcggtc 1260
ggaaaagaat ttaataaatt agaacgtcgt atggaaaatt taaataaaaa agtcgatgat 1320
ggatttttag atatatggac gtataatgcg gaattattag tcttattaga aaatgaacgt 1380
acgttagatt ttcatgattc gaatgtcaaa aatttatatg aaaaagtcaa atcgcaatta 1440
aaaaataatg cgaaagaaat aggaaatgga tgttttgaat tttatcataa atgtaatgat 1500
gaatgtatgg aatcggtcaa aaatggaacg tatgattatc cgaaatattc ggaagaatcg 1560
aaattaaatc gtgaaaaaat agatggagtc aaattagaat cgatgggagt ctataatata 1620
ttagcgatat attcgacggt cgcgtcgtcc ctagttcttt tagtctccct gggggcaatc 1680
agcttctgga tgtgttccaa tgggtcttta cagtgtagaa tatgcatcta agaccagaat 1740
ttcagaaata taaggaaaaa cacccttgtt tctact 1776
<210> 94
<211> 1458
<212> DNA
<213> 人工序列
<220>
<223> H1N2的NA-DO CDS + 5' 和 3'UTR
<400> 94
agcaaaagca ggagtttaaa atgaatccaa atcaaaagat aataacgatt ggctctgttt 60
ctcttactat tgccacaatg tgcttcctta tgcaaattgc catcctggta actaatgtaa 120
cattgcactt caatcaatat gaatgtaatt atccgccgaa taatcaagtc atattatgtg 180
aaccgacgat aatagaacgt aatataacgg aaatagtcta tttaacgaat acgacgatag 240
aaaaagaaat atgtccgaaa ttagcggaat atcgtaattg gtcgaaaccg caatgtaaaa 300
taacgggatt tgcgccgttt tcgaaagata attcgatacg tttatcggcg ggaggagata 360
tatgggtcac gcgtgaaccg tatgtctcgt gtgatccgga taaatgttat caatttgcgt 420
taggacaagg aacgacgtta aataatcgtc attcgaatga tacggtccat gatcgtacgc 480
cgtatcgcac gttattaatg aatgaattag gaataccgtt tcatttagga acgaaacaag 540
tctgtatagc gtggtcgtcg tcgtcgtgtc atgatggaaa agcgtggtta catgtctgta 600
taacgggaca tgatgaaaat gcgacggcgt cgataatata taatggacgt ttagtcgatt 660
cgataggatc gtggtcgaaa aaaatattac gtacgcaaga atcggaatgt gtctgtataa 720
atggaacgtg tacggtcgtc atgacggatg gatcggcgtc gggaatagcg gatacgaaaa 780
tattatttat agaagaagga aaaatagtcc atatatcgcc gttattagga tcggcgcaac 840
atgtcgaaga atgttcgtgt tatccgcgtt atccgggagt ccgttgtata tgtcgtgata 900
attggaaagg atcgaatcgt ccggtcgtcg atataaatgt caaagattat tcgatagtct 960
cgtcgtatgt ctgttcggga ttagtcggag atacgccgcg taaagatgat cgttcgtcgt 1020
cgtcggattg tttaaatccg aataatgaag aaggaggaca tggagtcaaa ggatgggcgt 1080
ttgatgatgg aaatgatgtc tggatgggac gtacgataaa tgaaacgtta cgttcgggat 1140
atgaaacgtt taaagtcata gaaggatggt cgaaaccgaa ttcgaaatta caaataaatc 1200
gtcaagtcat agtcgaacgt ggagatcgtt cgggatattc gggaatattt tcggtcgaag 1260
gaaaatcgtg tataaatcgt tgtttttatg tcgaattaat acgtggacgt aaacaagaaa 1320
ctgcagtatg gtggacgtca aacagtattg ttgtgttttg tggcacctca ggtacatatg 1380
gaacaggctc atggcctgat ggggcgaaca tcaatctcat gcctgtataa tttattcaaa 1440
aaactccttg tttctact 1458
<210> 95
<211> 1762
<212> DNA
<213> 人工序列
<220>
<223> H3N2的HA-DO CDS + 5' 和 3'UTR
<400> 95
agcaaaagca ggggatattt ctattaacca tgaagactat cattgctttt agctgcgttt 60
tatgtttgat tttcgctcaa aaacttcccg gaagtgacaa cagcatggca acgctgtgct 120
taggacatca tgcggtcccg aatggaacgt tagtcaaaac gataacggat gatcaaatag 180
aagtcacgaa tgcgacggaa ttagtccaat cgtcgtcgac gggacgtata tgtaattcgc 240
cgcatcaaat attagatgga aaaaattgta cgttaataga tgcgttatta ggagatccgc 300
attgtgatga ttttcaaaat aaagaatggg atttatttgt cgaacgttcg acggcgtatt 360
cgaattgtta tccgtattat gtcccggatt atgcgtcgtt acgttcgtta gtcgcgtcgt 420
cgggaacgtt agaatttacg caagaatcgt ttaattggac gggagtcgcg caagatggat 480
cgtcgtatgc gtgtcgtcgt gaatcggtca attcgttttt ttcgcgttta aattggttac 540
ataaattaga ttataaatat ccggcgttaa aagtcacgat gccgaataat gataaatttg 600
ataaattata tatatgggga gtccatcatc cgggaacgga tcgtgatcaa acgaatttat 660
atgtccaaac gtcgggacgt gtcacggtct cgacgaaacg ttcgcaacaa acggtcatac 720
cgaatatagg atcgcgtccg tgggtccgtg gagtctcgtc gataatatcg atatattgga 780
cgatagtcaa accgggagat atattattaa taaattcgac gggaaattta atagcgccgc 840
gtggatattt taaattacaa tcgggaaaat cgtcgataat gcgttcggat gcgccgatag 900
gaatatgtaa ttcggaatgt ataacgccga atggatcgat accgaatgat aaaccgtttc 960
aaaatgtcaa tcgtataacc tatggagcgt gtccgcgtta tgtcaaacaa aatacgttaa 1020
aattagcgac gggaatgcgt aatgtcccgg aaaaacaaac gcgtggaata tttggagcga 1080
tagcgggatt tatagaaaat ggatgggaag gaatggtcga tggatggtat ggatttcgtc 1140
atcaaaattc ggaaggaacg ggacaagcgg cggatttaaa atcgacgcgt gcggcgataa 1200
atcaaataac gggaaaatta aatcgtgtca taaaaaaaac gaatgaaaaa tttcatcaaa 1260
tagaaaaaga attttcggaa gtcgaaggac gtatacaaga tttagaaaaa tatgtcgaag 1320
atacgaaaat agatttatgg tcgtataatg cggaattatt agtcgcgtta gaaaatcaac 1380
atacgataga tttaacggat tcggaaatga ataaattatt tgaacgtacg cgtaaacaat 1440
tacgtgaaaa tgcggaagat atgggaaatg gatgttttaa aatatatcat aaatgtgata 1500
atgcgtgtat aggatcgata cgtaatggaa cgtatgatca tgatgtctat cgtgatgaag 1560
cgttaaataa tcgttttcaa ataaaaggag tccaattaaa atcgggatat aaagattgga 1620
tattatggat atcgtttgcg atatcgtgct ttttgctttg tgttgttctg ctggggttca 1680
ttatgtgggc ctgccaaaaa ggcaacatta ggtgcaacat ttgcatttga gtgcattaat 1740
taaaaacacc cttgtttcta ct 1762
<210> 96
<211> 1465
<212> DNA
<213> 人工序列
<220>
<223> H3N2的NA-DO CDS + 5' 和 3'UTR
<400> 96
agcaaaagca ggagtaaaga tgaatccaaa tcaaaagata ataacaattg gctctgtttc 60
tctcctcatt gccacaatat gcttccttat gcaaattgcc atcctggtaa ctactgtaac 120
attgcatttc aaacaacatg attgtaattc gtcgccgaat aatcaagtca tgttatgtga 180
accgacgata atagaacgta atacgacgga aatagtctat ttaacgaata taacgataga 240
aaaagaaata tgtccgaaat tagcggaata tcgtaattgg tcgaaaccgc aatgtaatat 300
aacgggattt gcgccgtttt cgaaagataa ttcgatacgt ttatcggcgg gaggagatat 360
atgggtcacg cgtgaaccgt atgtctcgtg tgatccggat aaatgttatc aatttgcgtt 420
aggacaagga acgacgttaa ataatggaca ttcgaatgat acggtccatg atcgtacgcc 480
gtatcgcacg ttattaatga atgaattagg agtcccgttt catttaggaa cgcgtcaagt 540
ctgtatagcg tggtcgtcgt cgtcgtgtca tgatggaaaa gcgtggttac atgtctgtat 600
aacgggagat gataaaaatg cgacggcgtc gtttatatat aatggacgtt tagtcgattc 660
gataggatcg tggtcgaaaa atatattacg tacgcaagaa tcggaatgtg tctgtataaa 720
tggaacgtgt acggtcgtca tgacggatgg atcggcgtcg ggaaaagcgg atacgaaagt 780
cttatttata gaagaaggaa aaatagtcca tatatcgacg ttatcgggat cggcgcaaca 840
tgtcgaagaa tgttcgtgtt atccgcgtta tccgggagtc cgttgtgtct gtcgtgataa 900
ttggaaagga tcgaatcgtc cgatagtcga tataaatgtc aaagattatt cgatagtctc 960
gtcgtatgtc tgttcgggat tagtcggaga tacgccgcgt aaaaatgatc gtttttcgtc 1020
gtcgcattgt caagatccga ataatgaaga aggaggacat ggagtcaaag gatgggcgtt 1080
tgatgatgga aatgatgtct ggatgggacg tacgataaat gaaaaattac gttcgggata 1140
tgaaacgttt aaagtcatag aaggatggtc gaaaccgaat tcgaaattac aaacgaatcg 1200
tcaagtcata gtcgaacgtg gaaatcgttc gggatattcg ggaatatttt cggtcgaagg 1260
aaaatcgtgt ataaatcgtt gtttttatgt cgaattaata cgtggacgta aagaagaaac 1320
taaagtctgg tggacctcaa acagtattgt tgtgctttgt ggcacctcag gtacatatgg 1380
aacaggctca tggcctgatg gggcggatat caatctcatg cctatataac tttcgcaatt 1440
ttagaaaaaa ctccttgttt ctact 1465
<210> 97
<211> 28
<212> DNA
<213> 人工序列
<220>
<223> Bm-HA-正向引物
<400> 97
tattcgtctc agggagcaaa agcagggg 28
<210> 98
<211> 21
<212> DNA
<213> 人工序列
<220>
<223> 3' 反向引物
<400> 98
gtagcctaca catattgtgt c 21
<210> 99
<211> 47
<212> DNA
<213> 人工序列
<220>
<223> 5' 正向引物
<400> 99
gacacaatat gtgtaggcta cgatatctta gcgatatatt cgacggt 47
<210> 100
<211> 35
<212> DNA
<213> 人工序列
<220>
<223> Bm-HA-R
<400> 100
atatcgtctc gtattagtag aaacaagggt gtttt 35
<210> 101
<211> 29
<212> DNA
<213> 人工序列
<220>
<223> H3胞外结构域正向引物
<400> 101
ctacatatgc acaaaaactt cccggaagt 29
<210> 102
<211> 26
<212> DNA
<213> 人工序列
<220>
<223> H3胞外结构域反向引物
<400> 102
taagatatct ttatatcccg atttta 26
<210> 103
<211> 21
<212> DNA
<213> 人工序列
<220>
<223> SEQ ID NOs: 98 & 99的重叠序列
<400> 103
gacacaatat gtgtaggcta c 21
<210> 104
<211> 325
<212> DNA
<213> 人工序列
<220>
<223> HA区段 (H1N2-DO) 的3'UTR, 信号序列 (SS), 跨膜结构域 (TMD), 胞质尾区结构域 (CTD), 和 5'UTR
<400> 104
tattcgtctc agggagcaaa agcaggggaa aaataaaagc aaccaaaatg aaagtaaaac 60
taatggttct gttatgtaca tttacagcta catatgcaga cacaatatgt gtaggctacg 120
atatcttagc gatatattcg acggtttagc gatatattcg acggtcgcgt cgtccctagt 180
tcttttagtc tccctggggg caatcagctt ctggatgtgt tccaatgggt ctttacagtg 240
tagaatatgc atctaagacc agaatttcag aaatataagg aaaaacaccc ttgtttctac 300
taatacgaga cgatatatcg gatcc 325
<210> 105
<211> 2100
<212> DNA
<213> 人工序列
<220>
<223> HA-DO (H1-H3嵌合体) - pHW2000的核苷酸351至2450
<400> 105
ggctaactag agaacccact gcttactggc ttatcgaaat taatacgact cactataggg 60
agacccaagc tgttaacgct agcagttaac cggagtactg gtcgacctcc gaagttgggg 120
gggagcaaaa gcaggggaaa aataaaagca accaaaatga aagtaaaact aatggttctg 180
ttatgtacat ttacagctac atatgcacaa aaacttcccg gaagtgacaa cagcatggca 240
acgctgtgct taggacatca tgcggtcccg aatggaacgt tagtcaaaac gataacggat 300
gatcaaatag aagtcacgaa tgcgacggaa ttagtccaat cgtcgtcgac gggacgtata 360
tgtaattcgc cgcatcaaat attagatgga aaaaattgta cgttaataga tgcgttatta 420
ggagatccgc attgtgatga ttttcaaaat aaagaatggg atttatttgt cgaacgttcg 480
acggcgtatt cgaattgtta tccgtattat gtcccggatt atgcgtcgtt acgttcgtta 540
gtcgcgtcgt cgggaacgtt agaatttacg caagaatcgt ttaattggac gggagtcgcg 600
caagatggat cgtcgtatgc gtgtcgtcgt gaatcggtca attcgttttt ttcgcgttta 660
aattggttac ataaattaga ttataaatat ccggcgttaa aagtcacgat gccgaataat 720
gataaatttg ataaattata tatatgggga gtccatcatc cgggaacgga tcgtgatcaa 780
acgaatttat atgtccaaac gtcgggacgt gtcacggtct cgacgaaacg ttcgcaacaa 840
acggtcatac cgaatatagg atcgcgtccg tgggtccgtg gagtctcgtc gataatatcg 900
atatattgga cgatagtcaa accgggagat atattattaa taaattcgac gggaaattta 960
atagcgccgc gtggatattt taaattacaa tcgggaaaat cgtcgataat gcgttcggat 1020
gcgccgatag gaatatgtaa ttcggaatgt ataacgccga atggatcgat accgaatgat 1080
aaaccgtttc aaaatgtcaa tcgtataacc tatggagcgt gtccgcgtta tgtcaaacaa 1140
aatacgttaa aattagcgac gggaatgcgt aatgtcccgg aaaaacaaac gcgtggaata 1200
tttggagcga tagcgggatt tatagaaaat ggatgggaag gaatggtcga tggatggtat 1260
ggatttcgtc atcaaaattc ggaaggaacg ggacaagcgg cggatttaaa atcgacgcgt 1320
gcggcgataa atcaaataac gggaaaatta aatcgtgtca taaaaaaaac gaatgaaaaa 1380
tttcatcaaa tagaaaaaga attttcggaa gtcgaaggac gtatacaaga tttagaaaaa 1440
tatgtcgaag atacgaaaat agatttatgg tcgtataatg cggaattatt agtcgcgtta 1500
gaaaatcaac atacgataga tttaacggat tcggaaatga ataaattatt tgaacgtacg 1560
cgtaaacaat tacgtgaaaa tgcggaagat atgggaaatg gatgttttaa aatatatcat 1620
aaatgtgata atgcgtgtat aggatcgata cgtaatggaa cgtatgatca tgatgtctat 1680
cgtgatgaag cgttaaataa tcgttttcaa ataaaaggag tccaattaaa atcgggatat 1740
aaagatatct tagcgatata ttcgacggtc gcgtcgtccc tagttctttt agtctccctg 1800
ggggcaatca gcttctggat gtgttccaat gggtctttac agtgtagaat atgcatctaa 1860
gaccagaatt tcagaaatat aaggaaaaac acccttgttt ctactaataa cccggcggcc 1920
caaaatgccg actcggagcg aaagatatac ctcccccggg gccgggaggt cgcgtcaccg 1980
accacgccgc cggcccaggc gacgcgcgac acggacacct gtccccaaaa acgccaccat 2040
cgcagccaca cacggagcgc ccggggccct ctggtcaacc ccaggacaca cgcgggagca 2100
<210> 106
<211> 567
<212> PRT
<213> 人工序列
<220>
<223> HA-DO (H1-H3嵌合体)
<400> 106
Met Lys Val Lys Leu Met Val Leu Leu Cys Thr Phe Thr Ala Thr Tyr
1 5 10 15
Ala Gln Lys Leu Pro Gly Ser Asp Asn Ser Met Ala Thr Leu Cys Leu
20 25 30
Gly His His Ala Val Pro Asn Gly Thr Leu Val Lys Thr Ile Thr Asp
35 40 45
Asp Gln Ile Glu Val Thr Asn Ala Thr Glu Leu Val Gln Ser Ser Ser
50 55 60
Thr Gly Arg Ile Cys Asn Ser Pro His Gln Ile Leu Asp Gly Lys Asn
65 70 75 80
Cys Thr Leu Ile Asp Ala Leu Leu Gly Asp Pro His Cys Asp Asp Phe
85 90 95
Gln Asn Lys Glu Trp Asp Leu Phe Val Glu Arg Ser Thr Ala Tyr Ser
100 105 110
Asn Cys Tyr Pro Tyr Tyr Val Pro Asp Tyr Ala Ser Leu Arg Ser Leu
115 120 125
Val Ala Ser Ser Gly Thr Leu Glu Phe Thr Gln Glu Ser Phe Asn Trp
130 135 140
Thr Gly Val Ala Gln Asp Gly Ser Ser Tyr Ala Cys Arg Arg Glu Ser
145 150 155 160
Val Asn Ser Phe Phe Ser Arg Leu Asn Trp Leu His Lys Leu Asp Tyr
165 170 175
Lys Tyr Pro Ala Leu Lys Val Thr Met Pro Asn Asn Asp Lys Phe Asp
180 185 190
Lys Leu Tyr Ile Trp Gly Val His His Pro Gly Thr Asp Arg Asp Gln
195 200 205
Thr Asn Leu Tyr Val Gln Thr Ser Gly Arg Val Thr Val Ser Thr Lys
210 215 220
Arg Ser Gln Gln Thr Val Ile Pro Asn Ile Gly Ser Arg Pro Trp Val
225 230 235 240
Arg Gly Val Ser Ser Ile Ile Ser Ile Tyr Trp Thr Ile Val Lys Pro
245 250 255
Gly Asp Ile Leu Leu Ile Asn Ser Thr Gly Asn Leu Ile Ala Pro Arg
260 265 270
Gly Tyr Phe Lys Leu Gln Ser Gly Lys Ser Ser Ile Met Arg Ser Asp
275 280 285
Ala Pro Ile Gly Ile Cys Asn Ser Glu Cys Ile Thr Pro Asn Gly Ser
290 295 300
Ile Pro Asn Asp Lys Pro Phe Gln Asn Val Asn Arg Ile Thr Tyr Gly
305 310 315 320
Ala Cys Pro Arg Tyr Val Lys Gln Asn Thr Leu Lys Leu Ala Thr Gly
325 330 335
Met Arg Asn Val Pro Glu Lys Gln Thr Arg Gly Ile Phe Gly Ala Ile
340 345 350
Ala Gly Phe Ile Glu Asn Gly Trp Glu Gly Met Val Asp Gly Trp Tyr
355 360 365
Gly Phe Arg His Gln Asn Ser Glu Gly Thr Gly Gln Ala Ala Asp Leu
370 375 380
Lys Ser Thr Arg Ala Ala Ile Asn Gln Ile Thr Gly Lys Leu Asn Arg
385 390 395 400
Val Ile Lys Lys Thr Asn Glu Lys Phe His Gln Ile Glu Lys Glu Phe
405 410 415
Ser Glu Val Glu Gly Arg Ile Gln Asp Leu Glu Lys Tyr Val Glu Asp
420 425 430
Thr Lys Ile Asp Leu Trp Ser Tyr Asn Ala Glu Leu Leu Val Ala Leu
435 440 445
Glu Asn Gln His Thr Ile Asp Leu Thr Asp Ser Glu Met Asn Lys Leu
450 455 460
Phe Glu Arg Thr Arg Lys Gln Leu Arg Glu Asn Ala Glu Asp Met Gly
465 470 475 480
Asn Gly Cys Phe Lys Ile Tyr His Lys Cys Asp Asn Ala Cys Ile Gly
485 490 495
Ser Ile Arg Asn Gly Thr Tyr Asp His Asp Val Tyr Arg Asp Glu Ala
500 505 510
Leu Asn Asn Arg Phe Gln Ile Lys Gly Val Gln Leu Lys Ser Gly Tyr
515 520 525
Lys Asp Ile Leu Ala Ile Tyr Ser Thr Val Ala Ser Ser Leu Val Leu
530 535 540
Leu Val Ser Leu Gly Ala Ile Ser Phe Trp Met Cys Ser Asn Gly Ser
545 550 555 560
Leu Gln Cys Arg Ile Cys Ile
565
<210> 107
<211> 3259
<212> DNA
<213> 人工序列
<220>
<223> pHW2000质粒
<400> 107
actcactata gggagaccca agctgttaac gctagcagtt aaccggagta ctggtcgacc 60
tccgaagttg ggggggagga gacggtaccg tctccaataa cccggcggcc caaaatgccg 120
actcggagcg aaagatatac ctcccccggg gccgggaggt cgcgtcaccg accacgccgc 180
cggcccaggc gacgcgcgac acggacacct gtccccaaaa acgccaccat cgcagccaca 240
cacggagcgc ccggggccct ctggtcaacc ccaggacaca cgcgggagca gcgccgggcc 300
ggggacgccc tcccggcggt cacctaaatg ctagagctcg ctgatcagcc tcgactgtgc 360
cttctagttg ccagccatct gttgtttgcc cctcccccgt gccttccttg accctggaag 420
gtgccactcc cactgtcctt tcctaataaa atgaggaaat tgcatcgcat tgtctgagta 480
ggtgtcattc tattctgggg ggtggggtgg ggcaggacag caagggggag gattgggaag 540
acaatagcag gcatgctggg gatgcggtgg gctctatggc ttctgaggcg gaaagaacca 600
gctgcattaa tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgctcttc 660
cgcttgatga cctctagcta gagcttggcg taatcatggt catagctgtt tcctgtgtga 720
aattgttatc cgctcacaat tccacacaac atacgagccg gaagcataaa gtgtaaagcc 780
tggggtgcct aatgagtgag ctaactcaca ttaattgcgt tgcgctcact gcccgctttc 840
cagtcgggaa acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc ggggagaggc 900
ggtttgcgta ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg ctcggtcgtt 960
cggctgcggc gagcggtatc agctcactca aaggcggtaa tacggttatc cacagaatca 1020
ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag gaaccgtaaa 1080
aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca tcacaaaaat 1140
cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca ggcgtttccc 1200
cctggaagct ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc 1260
gcctttctcc cttcgggaag cgtggcgctt tctcatagct cacgctgtag gtatctcagt 1320
tcggtgtagg tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt tcagcccgac 1380
cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc cggtaagaca cgacttatcg 1440
ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg cggtgctaca 1500
gagttcttga agtggtggcc taactacggc tacactagaa gaacagtatt tggtatctgc 1560
gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc cggcaaacaa 1620
accaccgctg gtagcggtgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa 1680
ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac 1740
tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta 1800
aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt 1860
taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg ttcatccata 1920
gttgcctgac tccccgtcgt gtagataact acgatacggg agggcttacc atctggcccc 1980
agtgctgcaa tgataccgcg agacccacgc tcaccggctc cagatttatc agcaataaac 2040
cagccagccg gaagggccga gcgcagaagt ggtcctgcaa ctttatccgc ctccatccag 2100
tctattaatt gttgccggga agctagagta agtagttcgc cagttaatag tttgcgcaac 2160
gttgttgcca ttgctacagg catcgtggtg tcacgctcgt cgtttggtat ggcttcattc 2220
agctccggtt cccaacgatc aaggcgagtt acatgatccc ccatgttgtg caaaaaagcg 2280
gttagctcct tcggtcctcc gatcgttgtc agaagtaagt tggccgcagt gttatcactc 2340
atggttatgg cagcactgca taattctctt actgtcatgc catccgtaag atgcttttct 2400
gtgactggtg agtactcaac caagtcattc tgagaatagt gtatgcggcg accgagttgc 2460
tcttgcccgg cgtcaatacg ggataatacc gcgccacata gcagaacttt aaaagtgctc 2520
atcattggaa aacgttcttc ggggcgaaaa ctctcaagga tcttaccgct gttgagatcc 2580
agttcgatgt aacccactcg tgcacccaac tgatcttcag catcttttac tttcaccagc 2640
gtttctgggt gagcaaaaac aggaaggcaa aatgccgcaa aaaagggaat aagggcgaca 2700
cggaaatgtt gaatactcat actcttcctt tttcaatatt attgaagcat ttatcagggt 2760
tattgtctca tgagcggata catatttgaa tgtatttaga aaaataaaca aataggggtt 2820
ccgcgcacat ttccccgaaa agtgccacct gacgtcatcg ccacctgacg tcgatatgcc 2880
aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 2940
catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 3000
catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg 3060
atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg 3120
ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt 3180
acggtgggag gtctatataa gcagagctct ctggctaact agagaaccca ctgcttactg 3240
gcttatcgaa attaatacg 3259
<210> 108
<211> 4130
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-TRIG-NS-DO
<400> 108
gaaaagtgcc acctgacgtc atcgccacct gacgtcgata tgccaagtac gccccctatt 60
gacgtcaatg acggtaaatg gcccgcctgg cattatgccc agtacatgac cttatgggac 120
tttcctactt ggcagtacat ctacgtatta gtcatcgcta ttaccatggt gatgcggttt 180
tggcagtaca tcaatgggcg tggatagcgg tttgactcac ggggatttcc aagtctccac 240
cccattgacg tcaatgggag tttgttttgg caccaaaatc aacgggactt tccaaaatgt 300
cgtaacaact ccgccccatt gacgcaaatg ggcggtaggc gtgtacggtg ggaggtctat 360
ataagcagag ctctctggct aactagagaa cccactgctt actggcttat cgaaattaat 420
acgactcact atagggagac ccaagctgtt aacgctagca gttaaccgga gtactggtcg 480
acctccgaag ttggggggga gcaaaagcag ggtgacaaag acataatgga ctccaatact 540
gtgtcaagct ttcaggtaga ctgtttcctt tggcacatcc gcaaacgatt tgcagacaat 600
ggattgggtg atgccccatt ccttgatcgg ctccgccgag atcaaaaatc gttaaaagga 660
cgtggaaata cgttatcgtt agatatagaa acggcgacgc tagtcggaaa acaaatagtc 720
gaatggatat taaaagaaga atcgtcggat atattaaaaa tgacgatagc gtcggtcccg 780
acgtcgcgtt atttagcgga tatgacgtta gaagaaatgt cgcgtgattg gtttatgtta 840
atgccgcgtc aaaaaataat aggaccgtta tgtgtccgtg tcgatcaagc gataatggaa 900
aaaaatataa tattaaaagc gaatttttcg gtcatattta atcgtttaga aacgttaata 960
ttattacgtg cgtttacgga ggagggagca atcgttggag aaatttcacc attaccttat 1020
cttccaggac atactaatga ggatgtcaaa aatgcagttg gggtcctcat cggagggctt 1080
gaatggaatg gtaacacggt tcgaggctct gaaaatctac agagattcgc ttggagaaac 1140
cataatgagg atgggagatc ttcactacct ccagaacaga aatgaaaagt ggcgagagca 1200
attgggacag aaatttgagg aaataagatg gttaattgaa gaaatacggc acagattgaa 1260
agcgacagaa aatagtttcg agcaaataac atttatgcaa gccttacaac tactgcttga 1320
agtagaacaa gagataagga ctttctcgtt tcagcttatt taatgataaa aaacaccctt 1380
gtttctacta ataacccggc ggcccaaaat gccgactcgg agcgaaagat atacctcccc 1440
cggggccggg aggtcgcgtc accgaccacg ccgccggccc aggcgacgcg cgacacggac 1500
acctgtcccc aaaaacgcca ccatcgcagc cacacacgga gcgcccgggg ccctctggtc 1560
aaccccagga cacacgcggg agcagcgccg ggccggggac gccctcccgg cggtcaccta 1620
aatgctagag ctcgctgatc agcctcgact gtgccttcta gttgccagcc atctgttgtt 1680
tgcccctccc ccgtgccttc cttgaccctg gaaggtgcca ctcccactgt cctttcctaa 1740
taaaatgagg aaattgcatc gcattgtctg agtaggtgtc attctattct ggggggtggg 1800
gtggggcagg acagcaaggg ggaggattgg gaagacaata gcaggcatgc tggggatgcg 1860
gtgggctcta tggcttctga ggcggaaaga accagctgca ttaatgaatc ggccaacgcg 1920
cggggagagg cggtttgcgt attgggcgct cttccgcttg atgacctcta gctagagctt 1980
ggcgtaatca tggtcatagc tgtttcctgt gtgaaattgt tatccgctca caattccaca 2040
caacatacga gccggaagca taaagtgtaa agcctggggt gcctaatgag tgagctaact 2100
cacattaatt gcgttgcgct cactgcccgc tttccagtcg ggaaacctgt cgtgccagct 2160
gcattaatga atcggccaac gcgcggggag aggcggtttg cgtattgggc gctcttccgc 2220
ttcctcgctc actgactcgc tgcgctcggt cgttcggctg cggcgagcgg tatcagctca 2280
ctcaaaggcg gtaatacggt tatccacaga atcaggggat aacgcaggaa agaacatgtg 2340
agcaaaaggc cagcaaaagg ccaggaaccg taaaaaggcc gcgttgctgg cgtttttcca 2400
taggctccgc ccccctgacg agcatcacaa aaatcgacgc tcaagtcaga ggtggcgaaa 2460
cccgacagga ctataaagat accaggcgtt tccccctgga agctccctcg tgcgctctcc 2520
tgttccgacc ctgccgctta ccggatacct gtccgccttt ctcccttcgg gaagcgtggc 2580
gctttctcat agctcacgct gtaggtatct cagttcggtg taggtcgttc gctccaagct 2640
gggctgtgtg cacgaacccc ccgttcagcc cgaccgctgc gccttatccg gtaactatcg 2700
tcttgagtcc aacccggtaa gacacgactt atcgccactg gcagcagcca ctggtaacag 2760
gattagcaga gcgaggtatg taggcggtgc tacagagttc ttgaagtggt ggcctaacta 2820
cggctacact agaagaacag tatttggtat ctgcgctctg ctgaagccag ttaccttcgg 2880
aaaaagagtt ggtagctctt gatccggcaa acaaaccacc gctggtagcg gtggtttttt 2940
tgtttgcaag cagcagatta cgcgcagaaa aaaaggatct caagaagatc ctttgatctt 3000
ttctacgggg tctgacgctc agtggaacga aaactcacgt taagggattt tggtcatgag 3060
attatcaaaa aggatcttca cctagatcct tttaaattaa aaatgaagtt ttaaatcaat 3120
ctaaagtata tatgagtaaa cttggtctga cagttaccaa tgcttaatca gtgaggcacc 3180
tatctcagcg atctgtctat ttcgttcatc catagttgcc tgactccccg tcgtgtagat 3240
aactacgata cgggagggct taccatctgg ccccagtgct gcaatgatac cgcgagaccc 3300
acgctcaccg gctccagatt tatcagcaat aaaccagcca gccggaaggg ccgagcgcag 3360
aagtggtcct gcaactttat ccgcctccat ccagtctatt aattgttgcc gggaagctag 3420
agtaagtagt tcgccagtta atagtttgcg caacgttgtt gccattgcta caggcatcgt 3480
ggtgtcacgc tcgtcgtttg gtatggcttc attcagctcc ggttcccaac gatcaaggcg 3540
agttacatga tcccccatgt tgtgcaaaaa agcggttagc tccttcggtc ctccgatcgt 3600
tgtcagaagt aagttggccg cagtgttatc actcatggtt atggcagcac tgcataattc 3660
tcttactgtc atgccatccg taagatgctt ttctgtgact ggtgagtact caaccaagtc 3720
attctgagaa tagtgtatgc ggcgaccgag ttgctcttgc ccggcgtcaa tacgggataa 3780
taccgcgcca catagcagaa ctttaaaagt gctcatcatt ggaaaacgtt cttcggggcg 3840
aaaactctca aggatcttac cgctgttgag atccagttcg atgtaaccca ctcgtgcacc 3900
caactgatct tcagcatctt ttactttcac cagcgtttct gggtgagcaa aaacaggaag 3960
gcaaaatgcc gcaaaaaagg gaataagggc gacacggaaa tgttgaatac tcatactctt 4020
cctttttcaa tattattgaa gcatttatca gggttattgt ctcatgagcg gatacatatt 4080
tgaatgtatt tagaaaaata aacaaatagg ggttccgcgc acatttcccc 4130
<210> 109
<211> 5018
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-H1N1-HA-DO
<400> 109
ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtcatcgc cacctgacgt 60
cgatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 120
tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 180
cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 240
ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggcacca 300
aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 360
taggcgtgta cggtgggagg tctatataag cagagctctc tggctaacta gagaacccac 420
tgcttactgg cttatcgaaa ttaatacgac tcactatagg gagacccaag ctgttaacgc 480
tagcagttaa ccggagtact ggtcgacctc cgaagttggg ggggagcaaa agcaggggaa 540
aataaaagca accaaaatga aggcaatact agtagttctg ctatatacat ttgcaacctc 600
aaatgcagac acattatgta taggttatca tgcgaacaat tcaacagata cggtcgatac 660
ggtcttagaa aaaaatgtca cggtcacgca ttcggtcaat ttattagaag ataaacataa 720
tggaaaatta tgtaaattac gtggagtcgc gccgttacat ttaggaaaat gtaatatagc 780
gggatggata ttaggaaatc cggaatgtga atcgttatcg acggcgtcgt cgtggtcgta 840
tatagtcgaa acgtcgtcgt cgggaaatgg aacgtgttat ccgggagatt ttatagatta 900
tgaagaatta cgtgaacaat tatcgtcggt ctcgtcgttt gaacgttttg aaatatttcc 960
gaaaacgtcg tcgtggccga atcatgaatc gaataaagga gtcacggcgg cgtgtccgca 1020
tgcgggagaa aaatcgtttt ataaaaattt aatatggcta gtcaaaaaag gaaattcgta 1080
tccgaaatta tcgaaatcgt atataaatga taaaggaaaa gaagtcttag tcttatgggg 1140
aatacatcat ccgtcgacgt cggcggatca acaatcgtta tatcaaaatg cggatgcgta 1200
tgtctttgtc ggaacgtcgc gttattcgaa aaaatttaaa ccggaaatag cgatacgtcc 1260
gaaagtccgt gatcaagaag gacgcatgaa ttattattgg acgctagtcg aaccgggaga 1320
taaaataacg tttgaagcga cgggaaattt agtcgtcccg cgttatgcgt ttgcgatgga 1380
acgtaatgcg ggatcgggaa taataatatc ggatacgccg gtccatgatt gtaatacgac 1440
gtgtcaaacg ccgaaaggag cgataaatac gtcgttaccg tttcaaaata tacatccgat 1500
aacgatagga aaatgtccga aatatgtcaa atcgacgaaa ttacgtttag cgacgggatt 1560
acgtaatgtc ccgtcgatac aatcgcgtgg attatttgga gcgatagcgg gatttataga 1620
aggaggatgg acgggaatgg tcgatggatg gtatggatat catcatcaaa atgaacaagg 1680
atcgggatat gcggcggatt taaaatcgac gcaaaatgcg atagatgaaa taacgaataa 1740
agtcaattcg gtcatagaaa aaatgaatac gcaatttacg gcggtcggaa aagaatttaa 1800
tcatttagaa aaacgtatag aaaatttaaa taaaaaagtc gatgatggat ttttagatat 1860
atggacgtat aatgcggaat tattagtctt attagaaaat gaacgtacgt tagattatca 1920
tgattcgaat gtcaaaaatt tatatgaaaa agtccgttcg caattaaaaa ataatgcgaa 1980
agaaatagga aatggatgtt ttgaatttta tcataaatgt gataatacgt gtatggaatc 2040
ggtcaaaaat ggaacgtatg attatccgaa atattcggaa gaagcgaaat taaatcgtga 2100
agaaatagat ggagtcaaat tagaatcgac gcgtatatat caaatattag cgatatattc 2160
gacggtcgcg tcgtcattgg tactggtagt ctccctgggg gcaatcagtt tctggatgtg 2220
ctctaatggg tctctacagt gtagaatatg tatttaacat taggatttca gaaacatgag 2280
aaaaaacacc cttgtttcta ctaataaccc ggcggcccaa aatgccgact cggagcgaaa 2340
gatatacctc ccccggggcc gggaggtcgc gtcaccgacc acgccgccgg cccaggcgac 2400
gcgcgacacg gacacctgtc cccaaaaacg ccaccatcgc agccacacac ggagcgcccg 2460
gggccctctg gtcaacccca ggacacacgc gggagcagcg ccgggccggg gacgccctcc 2520
cggcggtcac ctaaatgcta gagctcgctg atcagcctcg actgtgcctt ctagttgcca 2580
gccatctgtt gtttgcccct cccccgtgcc ttccttgacc ctggaaggtg ccactcccac 2640
tgtcctttcc taataaaatg aggaaattgc atcgcattgt ctgagtaggt gtcattctat 2700
tctggggggt ggggtggggc aggacagcaa gggggaggat tgggaagaca atagcaggca 2760
tgctggggat gcggtgggct ctatggcttc tgaggcggaa agaaccagct gcattaatga 2820
atcggccaac gcgcggggag aggcggtttg cgtattgggc gctcttccgc ttgatgacct 2880
ctagctagag cttggcgtaa tcatggtcat agctgtttcc tgtgtgaaat tgttatccgc 2940
tcacaattcc acacaacata cgagccggaa gcataaagtg taaagcctgg ggtgcctaat 3000
gagtgagcta actcacatta attgcgttgc gctcactgcc cgctttccag tcgggaaacc 3060
tgtcgtgcca gctgcattaa tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg 3120
ggcgctcttc cgcttcctcg ctcactgact cgctgcgctc ggtcgttcgg ctgcggcgag 3180
cggtatcagc tcactcaaag gcggtaatac ggttatccac agaatcaggg gataacgcag 3240
gaaagaacat gtgagcaaaa ggccagcaaa aggccaggaa ccgtaaaaag gccgcgttgc 3300
tggcgttttt ccataggctc cgcccccctg acgagcatca caaaaatcga cgctcaagtc 3360
agaggtggcg aaacccgaca ggactataaa gataccaggc gtttccccct ggaagctccc 3420
tcgtgcgctc tcctgttccg accctgccgc ttaccggata cctgtccgcc tttctccctt 3480
cgggaagcgt ggcgctttct catagctcac gctgtaggta tctcagttcg gtgtaggtcg 3540
ttcgctccaa gctgggctgt gtgcacgaac cccccgttca gcccgaccgc tgcgccttat 3600
ccggtaacta tcgtcttgag tccaacccgg taagacacga cttatcgcca ctggcagcag 3660
ccactggtaa caggattagc agagcgaggt atgtaggcgg tgctacagag ttcttgaagt 3720
ggtggcctaa ctacggctac actagaagaa cagtatttgg tatctgcgct ctgctgaagc 3780
cagttacctt cggaaaaaga gttggtagct cttgatccgg caaacaaacc accgctggta 3840
gcggtggttt ttttgtttgc aagcagcaga ttacgcgcag aaaaaaagga tctcaagaag 3900
atcctttgat cttttctacg gggtctgacg ctcagtggaa cgaaaactca cgttaaggga 3960
ttttggtcat gagattatca aaaaggatct tcacctagat ccttttaaat taaaaatgaa 4020
gttttaaatc aatctaaagt atatatgagt aaacttggtc tgacagttac caatgcttaa 4080
tcagtgaggc acctatctca gcgatctgtc tatttcgttc atccatagtt gcctgactcc 4140
ccgtcgtgta gataactacg atacgggagg gcttaccatc tggccccagt gctgcaatga 4200
taccgcgaga cccacgctca ccggctccag atttatcagc aataaaccag ccagccggaa 4260
gggccgagcg cagaagtggt cctgcaactt tatccgcctc catccagtct attaattgtt 4320
gccgggaagc tagagtaagt agttcgccag ttaatagttt gcgcaacgtt gttgccattg 4380
ctacaggcat cgtggtgtca cgctcgtcgt ttggtatggc ttcattcagc tccggttccc 4440
aacgatcaag gcgagttaca tgatccccca tgttgtgcaa aaaagcggtt agctccttcg 4500
gtcctccgat cgttgtcaga agtaagttgg ccgcagtgtt atcactcatg gttatggcag 4560
cactgcataa ttctcttact gtcatgccat ccgtaagatg cttttctgtg actggtgagt 4620
actcaaccaa gtcattctga gaatagtgta tgcggcgacc gagttgctct tgcccggcgt 4680
caatacggga taataccgcg ccacatagca gaactttaaa agtgctcatc attggaaaac 4740
gttcttcggg gcgaaaactc tcaaggatct taccgctgtt gagatccagt tcgatgtaac 4800
ccactcgtgc acccaactga tcttcagcat cttttacttt caccagcgtt tctgggtgag 4860
caaaaacagg aaggcaaaat gccgcaaaaa agggaataag ggcgacacgg aaatgttgaa 4920
tactcatact cttccttttt caatattatt gaagcattta tcagggttat tgtctcatga 4980
gcggatacat atttgaatgt atttagaaaa ataaacaa 5018
<210> 110
<211> 4698
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-H1N1-NA-DO
<400> 110
caaatagggg ttccgcgcac atttccccga aaagtgccac ctgacgtcat cgccacctga 60
cgtcgatatg ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca 120
ttatgcccag tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt 180
catcgctatt accatggtga tgcggttttg gcagtacatc aatgggcgtg gatagcggtt 240
tgactcacgg ggatttccaa gtctccaccc cattgacgtc aatgggagtt tgttttggca 300
ccaaaatcaa cgggactttc caaaatgtcg taacaactcc gccccattga cgcaaatggg 360
cggtaggcgt gtacggtggg aggtctatat aagcagagct ctctggctaa ctagagaacc 420
cactgcttac tggcttatcg aaattaatac gactcactat agggagaccc aagctgttaa 480
cgctagcagt taaccggagt actggtcgac ctccgaagtt gggggggagc aaaagcagga 540
gtttaaaatg aatccaaacc aaaagataat aaccattggt tcggtctgta tgacaattgg 600
aatggctaac ttaatattac aaattggaaa cataatctca atatggattt cgcattcgat 660
acaattagga aatcaaaatc aaatagaaac gtgtaatcaa tcggtcataa cgtatgaaaa 720
taatacgtgg gtcaatcaaa cgtatgtcaa tatatcgaat acgaattttg cggcgggaca 780
atcggtcgta tcggtcaaat tagcgggaaa ttcgtcgtta tgtccggtct cgggatgggc 840
gatatattcg aaagataatt cggtccgtat aggatcgaaa ggagatgtct ttgtcatacg 900
tgaaccgttt atatcgtgtt cgccgttaga atgtcgtacg ttttttttaa cgcaaggagc 960
gttattaaat gataaacatt cgaatggaac gataaaagat cgttcgccgt atcgtacgtt 1020
aatgtcgtgt ccgataggag aagtcccgtc gccgtataat tcgcgttttg aatcggtcgc 1080
gtggtcggcg tcggcgtgtc atgatggaat aaattggtta acgataggaa tatcgggacc 1140
ggataatgga gcggtcgcgg tcttaaaata taatggaata ataacggata cgataaaatc 1200
gtggcgtaat aatatattac gtacgcaaga atcggaatgt gcgtgtgtca atggatcgtg 1260
ttttacggtc atgacggatg gaccgtcgaa tggacaagcg tcgtataaaa tatttcgtat 1320
agaaaaagga aaaatagtca aatcggtcga aatgaatgcg ccgaattatc attatgaaga 1380
atgttcgtgt tatccggatt cgtcggaaat aacgtgtgtc tgtcgtgata attggcatgg 1440
atcgaatcgt ccgtgggtct cgtttaatca aaatttagaa tatcaaatag gatatatatg 1500
ttcgggaata tttggagata atccgcgtcc gaatgataaa acgggatcgt gtggaccggt 1560
ctcgtcgaat ggagcgaatg gagtcaaagg attttcgttt aaatatggaa atggagtctg 1620
gataggacgt acgaaatcga tatcgtcgcg taatggattt gaaatgatat gggatccgaa 1680
tggatggacg ggaacggata ataatttttc gataaaacaa gatatagtcg gaataaatga 1740
atggtcggga tattcgggat cgtttgtcca acatccggaa ttaacgggat tagattgtat 1800
acgtccgtgt ttttgggtcg aattaatacg tggacgtccg aaagaaaata cgatatggac 1860
tagcgggagc agcatatcct tttgtggtgt aaacagtgac actgtgggtt ggtcttggcc 1920
agacggtgct gagttgccat ttaccattga caagtaattt gttcaaaaaa ctccttgttt 1980
ctactaataa cccggcggcc caaaatgccg actcggagcg aaagatatac ctcccccggg 2040
gccgggaggt cgcgtcaccg accacgccgc cggcccaggc gacgcgcgac acggacacct 2100
gtccccaaaa acgccaccat cgcagccaca cacggagcgc ccggggccct ctggtcaacc 2160
ccaggacaca cgcgggagca gcgccgggcc ggggacgccc tcccggcggt cacctaaatg 2220
ctagagctcg ctgatcagcc tcgactgtgc cttctagttg ccagccatct gttgtttgcc 2280
cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt tcctaataaa 2340
atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg ggtggggtgg 2400
ggcaggacag caagggggag gattgggaag acaatagcag gcatgctggg gatgcggtgg 2460
gctctatggc ttctgaggcg gaaagaacca gctgcattaa tgaatcggcc aacgcgcggg 2520
gagaggcggt ttgcgtattg ggcgctcttc cgcttgatga cctctagcta gagcttggcg 2580
taatcatggt catagctgtt tcctgtgtga aattgttatc cgctcacaat tccacacaac 2640
atacgagccg gaagcataaa gtgtaaagcc tggggtgcct aatgagtgag ctaactcaca 2700
ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat 2760
taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc ttccgcttcc 2820
tcgctcactg actcgctgcg ctcggtcgtt cggctgcggc gagcggtatc agctcactca 2880
aaggcggtaa tacggttatc cacagaatca ggggataacg caggaaagaa catgtgagca 2940
aaaggccagc aaaaggccag gaaccgtaaa aaggccgcgt tgctggcgtt tttccatagg 3000
ctccgccccc ctgacgagca tcacaaaaat cgacgctcaa gtcagaggtg gcgaaacccg 3060
acaggactat aaagatacca ggcgtttccc cctggaagct ccctcgtgcg ctctcctgtt 3120
ccgaccctgc cgcttaccgg atacctgtcc gcctttctcc cttcgggaag cgtggcgctt 3180
tctcatagct cacgctgtag gtatctcagt tcggtgtagg tcgttcgctc caagctgggc 3240
tgtgtgcacg aaccccccgt tcagcccgac cgctgcgcct tatccggtaa ctatcgtctt 3300
gagtccaacc cggtaagaca cgacttatcg ccactggcag cagccactgg taacaggatt 3360
agcagagcga ggtatgtagg cggtgctaca gagttcttga agtggtggcc taactacggc 3420
tacactagaa gaacagtatt tggtatctgc gctctgctga agccagttac cttcggaaaa 3480
agagttggta gctcttgatc cggcaaacaa accaccgctg gtagcggtgg tttttttgtt 3540
tgcaagcagc agattacgcg cagaaaaaaa ggatctcaag aagatccttt gatcttttct 3600
acggggtctg acgctcagtg gaacgaaaac tcacgttaag ggattttggt catgagatta 3660
tcaaaaagga tcttcaccta gatcctttta aattaaaaat gaagttttaa atcaatctaa 3720
agtatatatg agtaaacttg gtctgacagt taccaatgct taatcagtga ggcacctatc 3780
tcagcgatct gtctatttcg ttcatccata gttgcctgac tccccgtcgt gtagataact 3840
acgatacggg agggcttacc atctggcccc agtgctgcaa tgataccgcg agacccacgc 3900
tcaccggctc cagatttatc agcaataaac cagccagccg gaagggccga gcgcagaagt 3960
ggtcctgcaa ctttatccgc ctccatccag tctattaatt gttgccggga agctagagta 4020
agtagttcgc cagttaatag tttgcgcaac gttgttgcca ttgctacagg catcgtggtg 4080
tcacgctcgt cgtttggtat ggcttcattc agctccggtt cccaacgatc aaggcgagtt 4140
acatgatccc ccatgttgtg caaaaaagcg gttagctcct tcggtcctcc gatcgttgtc 4200
agaagtaagt tggccgcagt gttatcactc atggttatgg cagcactgca taattctctt 4260
actgtcatgc catccgtaag atgcttttct gtgactggtg agtactcaac caagtcattc 4320
tgagaatagt gtatgcggcg accgagttgc tcttgcccgg cgtcaatacg ggataatacc 4380
gcgccacata gcagaacttt aaaagtgctc atcattggaa aacgttcttc ggggcgaaaa 4440
ctctcaagga tcttaccgct gttgagatcc agttcgatgt aacccactcg tgcacccaac 4500
tgatcttcag catcttttac tttcaccagc gtttctgggt gagcaaaaac aggaaggcaa 4560
aatgccgcaa aaaagggaat aagggcgaca cggaaatgtt gaatactcat actcttcctt 4620
tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata catatttgaa 4680
tgtatttaga aaaataaa 4698
<210> 111
<211> 5016
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-H1N2-HA-DO
<400> 111
ataggggttc cgcgcacatt tccccgaaaa gtgccacctg acgtcatcgc cacctgacgt 60
cgatatgcca agtacgcccc ctattgacgt caatgacggt aaatggcccg cctggcatta 120
tgcccagtac atgaccttat gggactttcc tacttggcag tacatctacg tattagtcat 180
cgctattacc atggtgatgc ggttttggca gtacatcaat gggcgtggat agcggtttga 240
ctcacgggga tttccaagtc tccaccccat tgacgtcaat gggagtttgt tttggcacca 300
aaatcaacgg gactttccaa aatgtcgtaa caactccgcc ccattgacgc aaatgggcgg 360
taggcgtgta cggtgggagg tctatataag cagagctctc tggctaacta gagaacccac 420
tgcttactgg cttatcgaaa ttaatacgac tcactatagg gagacccaag ctgttaacgc 480
tagcagttaa ccggagtact ggtcgacctc cgaagttggg ggggagcaaa agcaggggaa 540
aaataaaagc aaccaaaatg aaagtaaaac taatggttct gttatgtaca tttacagcta 600
catatgcaga cacaatatgt gtaggctacc atgccaacaa ctcaactgat acggtcgata 660
cggtcttaga aaaaaatgtc acggtcacgc attcggtcaa tttattagaa gattcgcata 720
atggaaaatt atgtttatta aaaggaatag cgccgttaca attaggatcg tgttcggtcg 780
cgggatggat attaggaaat ccggaatgtg aattattaat atcgaaagaa tcgtggtcgt 840
atatagtcga aacgccgaat ccggaaaatg gaacgtgtta tccgggatat tttacggatt 900
atgaagaatt acgtgaacaa ttatcgtcgg tctcgtcgtt taaacgtttt gaaatatttc 960
cgaaagaatc gtcgtggccg aatcatacgg tcacgggagt ctcgtcgtcg tgttcgcata 1020
atggaaaatc gtcgttttat cgtaatttat tatggttaac ggtcaaaaat ggattatatc 1080
cgaatttatc gaaatcgtat acgaataaaa aagaaaaaga agtcttagtc ttatggggag 1140
tccatcatcc gtcgaatata ggagatcaac gtgcgttata tcatacggaa aatgcgtatg 1200
tctcggtcgt atcgtcgcat tattcgcgtc gttttacgcc ggaaatagcg aaacgtccga 1260
aagtccgtaa tcaagaagga cgtataaatt attattggac gttattagaa ccgggagata 1320
cgataatatt tgaagcgaat ggaaatttaa tagcgccgcg ttatgcgttt gaattatcga 1380
aaggatttgg atcgggaata ataacgtcga atgcgccgat gggagaatgt aatgcgaaat 1440
gtcaaacgcc gcaaggagcg ataaattcgt cgttaccgtt tcaaaatgtc catccggtca 1500
cgataggaga atgtccgaaa tatgtcaaat cggcgaaatt acgtatggtc acgggattac 1560
gtaatacgcc gtcgatacaa tcgcgtggat tatttggagc gatagcggga tttatagaag 1620
gaggatggac gggaatggtc gatggatggt atggatatca tcatcaaaat gaacaaggat 1680
cgggatatgc ggcggatcaa caatcgacgc aaaatgcgat aaatggaata acgaataaag 1740
tcaattcggt catagaaaaa atgaatacgc aatttacggc ggtcggaaaa gaatttaata 1800
aattagaacg tcgtatggaa aatttaaata aaaaagtcga tgatggattt ttagatatat 1860
ggacgtataa tgcggaatta ttagtcttat tagaaaatga acgtacgtta gattttcatg 1920
attcgaatgt caaaaattta tatgaaaaag tcaaatcgca attaaaaaat aatgcgaaag 1980
aaataggaaa tggatgtttt gaattttatc ataaatgtaa tgatgaatgt atggaatcgg 2040
tcaaaaatgg aacgtatgat tatccgaaat attcggaaga atcgaaatta aatcgtgaaa 2100
aaatagatgg agtcaaatta gaatcgatgg gagtctataa tatattagcg atatattcga 2160
cggtcgcgtc gtccctagtt cttttagtct ccctgggggc aatcagcttc tggatgtgtt 2220
ccaatgggtc tttacagtgt agaatatgca tctaagacca gaatttcaga aatataagga 2280
aaaacaccct tgtttctact aataacccgg cggcccaaaa tgccgactcg gagcgaaaga 2340
tatacctccc ccggggccgg gaggtcgcgt caccgaccac gccgccggcc caggcgacgc 2400
gcgacacgga cacctgtccc caaaaacgcc accatcgcag ccacacacgg agcgcccggg 2460
gccctctggt caaccccagg acacacgcgg gagcagcgcc gggccgggga cgccctcccg 2520
gcggtcacct aaatgctaga gctcgctgat cagcctcgac tgtgccttct agttgccagc 2580
catctgttgt ttgcccctcc cccgtgcctt ccttgaccct ggaaggtgcc actcccactg 2640
tcctttccta ataaaatgag gaaattgcat cgcattgtct gagtaggtgt cattctattc 2700
tggggggtgg ggtggggcag gacagcaagg gggaggattg ggaagacaat agcaggcatg 2760
ctggggatgc ggtgggctct atggcttctg aggcggaaag aaccagctgc attaatgaat 2820
cggccaacgc gcggggagag gcggtttgcg tattgggcgc tcttccgctt gatgacctct 2880
agctagagct tggcgtaatc atggtcatag ctgtttcctg tgtgaaattg ttatccgctc 2940
acaattccac acaacatacg agccggaagc ataaagtgta aagcctgggg tgcctaatga 3000
gtgagctaac tcacattaat tgcgttgcgc tcactgcccg ctttccagtc gggaaacctg 3060
tcgtgccagc tgcattaatg aatcggccaa cgcgcgggga gaggcggttt gcgtattggg 3120
cgctcttccg cttcctcgct cactgactcg ctgcgctcgg tcgttcggct gcggcgagcg 3180
gtatcagctc actcaaaggc ggtaatacgg ttatccacag aatcagggga taacgcagga 3240
aagaacatgt gagcaaaagg ccagcaaaag gccaggaacc gtaaaaaggc cgcgttgctg 3300
gcgtttttcc ataggctccg cccccctgac gagcatcaca aaaatcgacg ctcaagtcag 3360
aggtggcgaa acccgacagg actataaaga taccaggcgt ttccccctgg aagctccctc 3420
gtgcgctctc ctgttccgac cctgccgctt accggatacc tgtccgcctt tctcccttcg 3480
ggaagcgtgg cgctttctca tagctcacgc tgtaggtatc tcagttcggt gtaggtcgtt 3540
cgctccaagc tgggctgtgt gcacgaaccc cccgttcagc ccgaccgctg cgccttatcc 3600
ggtaactatc gtcttgagtc caacccggta agacacgact tatcgccact ggcagcagcc 3660
actggtaaca ggattagcag agcgaggtat gtaggcggtg ctacagagtt cttgaagtgg 3720
tggcctaact acggctacac tagaagaaca gtatttggta tctgcgctct gctgaagcca 3780
gttaccttcg gaaaaagagt tggtagctct tgatccggca aacaaaccac cgctggtagc 3840
ggtggttttt ttgtttgcaa gcagcagatt acgcgcagaa aaaaaggatc tcaagaagat 3900
cctttgatct tttctacggg gtctgacgct cagtggaacg aaaactcacg ttaagggatt 3960
ttggtcatga gattatcaaa aaggatcttc acctagatcc ttttaaatta aaaatgaagt 4020
tttaaatcaa tctaaagtat atatgagtaa acttggtctg acagttacca atgcttaatc 4080
agtgaggcac ctatctcagc gatctgtcta tttcgttcat ccatagttgc ctgactcccc 4140
gtcgtgtaga taactacgat acgggagggc ttaccatctg gccccagtgc tgcaatgata 4200
ccgcgagacc cacgctcacc ggctccagat ttatcagcaa taaaccagcc agccggaagg 4260
gccgagcgca gaagtggtcc tgcaacttta tccgcctcca tccagtctat taattgttgc 4320
cgggaagcta gagtaagtag ttcgccagtt aatagtttgc gcaacgttgt tgccattgct 4380
acaggcatcg tggtgtcacg ctcgtcgttt ggtatggctt cattcagctc cggttcccaa 4440
cgatcaaggc gagttacatg atcccccatg ttgtgcaaaa aagcggttag ctccttcggt 4500
cctccgatcg ttgtcagaag taagttggcc gcagtgttat cactcatggt tatggcagca 4560
ctgcataatt ctcttactgt catgccatcc gtaagatgct tttctgtgac tggtgagtac 4620
tcaaccaagt cattctgaga atagtgtatg cggcgaccga gttgctcttg cccggcgtca 4680
atacgggata ataccgcgcc acatagcaga actttaaaag tgctcatcat tggaaaacgt 4740
tcttcggggc gaaaactctc aaggatctta ccgctgttga gatccagttc gatgtaaccc 4800
actcgtgcac ccaactgatc ttcagcatct tttactttca ccagcgtttc tgggtgagca 4860
aaaacaggaa ggcaaaatgc cgcaaaaaag ggaataaggg cgacacggaa atgttgaata 4920
ctcatactct tcctttttca atattattga agcatttatc agggttattg tctcatgagc 4980
ggatacatat ttgaatgtat ttagaaaaat aaacaa 5016
<210> 112
<211> 4698
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-H1N2-NA-DO
<400> 112
caaatagggg ttccgcgcac atttccccga aaagtgccac ctgacgtcat cgccacctga 60
cgtcgatatg ccaagtacgc cccctattga cgtcaatgac ggtaaatggc ccgcctggca 120
ttatgcccag tacatgacct tatgggactt tcctacttgg cagtacatct acgtattagt 180
catcgctatt accatggtga tgcggttttg gcagtacatc aatgggcgtg gatagcggtt 240
tgactcacgg ggatttccaa gtctccaccc cattgacgtc aatgggagtt tgttttggca 300
ccaaaatcaa cgggactttc caaaatgtcg taacaactcc gccccattga cgcaaatggg 360
cggtaggcgt gtacggtggg aggtctatat aagcagagct ctctggctaa ctagagaacc 420
cactgcttac tggcttatcg aaattaatac gactcactat agggagaccc aagctgttaa 480
cgctagcagt taaccggagt actggtcgac ctccgaagtt gggggggagc aaaagcagga 540
gtttaaaatg aatccaaatc aaaagataat aacgattggc tctgtttctc ttactattgc 600
cacaatgtgc ttccttatgc aaattgccat cctggtaact aatgtaacat tgcacttcaa 660
tcaatatgaa tgtaattatc cgccgaataa tcaagtcata ttatgtgaac cgacgataat 720
agaacgtaat ataacggaaa tagtctattt aacgaatacg acgatagaaa aagaaatatg 780
tccgaaatta gcggaatatc gtaattggtc gaaaccgcaa tgtaaaataa cgggatttgc 840
gccgttttcg aaagataatt cgatacgttt atcggcggga ggagatatat gggtcacgcg 900
tgaaccgtat gtctcgtgtg atccggataa atgttatcaa tttgcgttag gacaaggaac 960
gacgttaaat aatcgtcatt cgaatgatac ggtccatgat cgtacgccgt atcgcacgtt 1020
attaatgaat gaattaggaa taccgtttca tttaggaacg aaacaagtct gtatagcgtg 1080
gtcgtcgtcg tcgtgtcatg atggaaaagc gtggttacat gtctgtataa cgggacatga 1140
tgaaaatgcg acggcgtcga taatatataa tggacgttta gtcgattcga taggatcgtg 1200
gtcgaaaaaa atattacgta cgcaagaatc ggaatgtgtc tgtataaatg gaacgtgtac 1260
ggtcgtcatg acggatggat cggcgtcggg aatagcggat acgaaaatat tatttataga 1320
agaaggaaaa atagtccata tatcgccgtt attaggatcg gcgcaacatg tcgaagaatg 1380
ttcgtgttat ccgcgttatc cgggagtccg ttgtatatgt cgtgataatt ggaaaggatc 1440
gaatcgtccg gtcgtcgata taaatgtcaa agattattcg atagtctcgt cgtatgtctg 1500
ttcgggatta gtcggagata cgccgcgtaa agatgatcgt tcgtcgtcgt cggattgttt 1560
aaatccgaat aatgaagaag gaggacatgg agtcaaagga tgggcgtttg atgatggaaa 1620
tgatgtctgg atgggacgta cgataaatga aacgttacgt tcgggatatg aaacgtttaa 1680
agtcatagaa ggatggtcga aaccgaattc gaaattacaa ataaatcgtc aagtcatagt 1740
cgaacgtgga gatcgttcgg gatattcggg aatattttcg gtcgaaggaa aatcgtgtat 1800
aaatcgttgt ttttatgtcg aattaatacg tggacgtaaa caagaaactg cagtatggtg 1860
gacgtcaaac agtattgttg tgttttgtgg cacctcaggt acatatggaa caggctcatg 1920
gcctgatggg gcgaacatca atctcatgcc tgtataattt attcaaaaaa ctccttgttt 1980
ctactaataa cccggcggcc caaaatgccg actcggagcg aaagatatac ctcccccggg 2040
gccgggaggt cgcgtcaccg accacgccgc cggcccaggc gacgcgcgac acggacacct 2100
gtccccaaaa acgccaccat cgcagccaca cacggagcgc ccggggccct ctggtcaacc 2160
ccaggacaca cgcgggagca gcgccgggcc ggggacgccc tcccggcggt cacctaaatg 2220
ctagagctcg ctgatcagcc tcgactgtgc cttctagttg ccagccatct gttgtttgcc 2280
cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt tcctaataaa 2340
atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg ggtggggtgg 2400
ggcaggacag caagggggag gattgggaag acaatagcag gcatgctggg gatgcggtgg 2460
gctctatggc ttctgaggcg gaaagaacca gctgcattaa tgaatcggcc aacgcgcggg 2520
gagaggcggt ttgcgtattg ggcgctcttc cgcttgatga cctctagcta gagcttggcg 2580
taatcatggt catagctgtt tcctgtgtga aattgttatc cgctcacaat tccacacaac 2640
atacgagccg gaagcataaa gtgtaaagcc tggggtgcct aatgagtgag ctaactcaca 2700
ttaattgcgt tgcgctcact gcccgctttc cagtcgggaa acctgtcgtg ccagctgcat 2760
taatgaatcg gccaacgcgc ggggagaggc ggtttgcgta ttgggcgctc ttccgcttcc 2820
tcgctcactg actcgctgcg ctcggtcgtt cggctgcggc gagcggtatc agctcactca 2880
aaggcggtaa tacggttatc cacagaatca ggggataacg caggaaagaa catgtgagca 2940
aaaggccagc aaaaggccag gaaccgtaaa aaggccgcgt tgctggcgtt tttccatagg 3000
ctccgccccc ctgacgagca tcacaaaaat cgacgctcaa gtcagaggtg gcgaaacccg 3060
acaggactat aaagatacca ggcgtttccc cctggaagct ccctcgtgcg ctctcctgtt 3120
ccgaccctgc cgcttaccgg atacctgtcc gcctttctcc cttcgggaag cgtggcgctt 3180
tctcatagct cacgctgtag gtatctcagt tcggtgtagg tcgttcgctc caagctgggc 3240
tgtgtgcacg aaccccccgt tcagcccgac cgctgcgcct tatccggtaa ctatcgtctt 3300
gagtccaacc cggtaagaca cgacttatcg ccactggcag cagccactgg taacaggatt 3360
agcagagcga ggtatgtagg cggtgctaca gagttcttga agtggtggcc taactacggc 3420
tacactagaa gaacagtatt tggtatctgc gctctgctga agccagttac cttcggaaaa 3480
agagttggta gctcttgatc cggcaaacaa accaccgctg gtagcggtgg tttttttgtt 3540
tgcaagcagc agattacgcg cagaaaaaaa ggatctcaag aagatccttt gatcttttct 3600
acggggtctg acgctcagtg gaacgaaaac tcacgttaag ggattttggt catgagatta 3660
tcaaaaagga tcttcaccta gatcctttta aattaaaaat gaagttttaa atcaatctaa 3720
agtatatatg agtaaacttg gtctgacagt taccaatgct taatcagtga ggcacctatc 3780
tcagcgatct gtctatttcg ttcatccata gttgcctgac tccccgtcgt gtagataact 3840
acgatacggg agggcttacc atctggcccc agtgctgcaa tgataccgcg agacccacgc 3900
tcaccggctc cagatttatc agcaataaac cagccagccg gaagggccga gcgcagaagt 3960
ggtcctgcaa ctttatccgc ctccatccag tctattaatt gttgccggga agctagagta 4020
agtagttcgc cagttaatag tttgcgcaac gttgttgcca ttgctacagg catcgtggtg 4080
tcacgctcgt cgtttggtat ggcttcattc agctccggtt cccaacgatc aaggcgagtt 4140
acatgatccc ccatgttgtg caaaaaagcg gttagctcct tcggtcctcc gatcgttgtc 4200
agaagtaagt tggccgcagt gttatcactc atggttatgg cagcactgca taattctctt 4260
actgtcatgc catccgtaag atgcttttct gtgactggtg agtactcaac caagtcattc 4320
tgagaatagt gtatgcggcg accgagttgc tcttgcccgg cgtcaatacg ggataatacc 4380
gcgccacata gcagaacttt aaaagtgctc atcattggaa aacgttcttc ggggcgaaaa 4440
ctctcaagga tcttaccgct gttgagatcc agttcgatgt aacccactcg tgcacccaac 4500
tgatcttcag catcttttac tttcaccagc gtttctgggt gagcaaaaac aggaaggcaa 4560
aatgccgcaa aaaagggaat aagggcgaca cggaaatgtt gaatactcat actcttcctt 4620
tttcaatatt attgaagcat ttatcagggt tattgtctca tgagcggata catatttgaa 4680
tgtatttaga aaaataaa 4698
<210> 113
<211> 5002
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-H3N2-HA-DO
<400> 113
taaacaaata ggggttccgc gcacatttcc ccgaaaagtg ccacctgacg tcatcgccac 60
ctgacgtcga tatgccaagt acgcccccta ttgacgtcaa tgacggtaaa tggcccgcct 120
ggcattatgc ccagtacatg accttatggg actttcctac ttggcagtac atctacgtat 180
tagtcatcgc tattaccatg gtgatgcggt tttggcagta catcaatggg cgtggatagc 240
ggtttgactc acggggattt ccaagtctcc accccattga cgtcaatggg agtttgtttt 300
ggcaccaaaa tcaacgggac tttccaaaat gtcgtaacaa ctccgcccca ttgacgcaaa 360
tgggcggtag gcgtgtacgg tgggaggtct atataagcag agctctctgg ctaactagag 420
aacccactgc ttactggctt atcgaaatta atacgactca ctatagggag acccaagctg 480
ttaacgctag cagttaaccg gagtactggt cgacctccga agttgggggg gagcaaaagc 540
aggggatatt tctattaacc atgaagacta tcattgcttt tagctgcgtt ttatgtttga 600
ttttcgctca aaaacttccc ggaagtgaca acagcatggc aacgctgtgc ttaggacatc 660
atgcggtccc gaatggaacg ttagtcaaaa cgataacgga tgatcaaata gaagtcacga 720
atgcgacgga attagtccaa tcgtcgtcga cgggacgtat atgtaattcg ccgcatcaaa 780
tattagatgg aaaaaattgt acgttaatag atgcgttatt aggagatccg cattgtgatg 840
attttcaaaa taaagaatgg gatttatttg tcgaacgttc gacggcgtat tcgaattgtt 900
atccgtatta tgtcccggat tatgcgtcgt tacgttcgtt agtcgcgtcg tcgggaacgt 960
tagaatttac gcaagaatcg tttaattgga cgggagtcgc gcaagatgga tcgtcgtatg 1020
cgtgtcgtcg tgaatcggtc aattcgtttt tttcgcgttt aaattggtta cataaattag 1080
attataaata tccggcgtta aaagtcacga tgccgaataa tgataaattt gataaattat 1140
atatatgggg agtccatcat ccgggaacgg atcgtgatca aacgaattta tatgtccaaa 1200
cgtcgggacg tgtcacggtc tcgacgaaac gttcgcaaca aacggtcata ccgaatatag 1260
gatcgcgtcc gtgggtccgt ggagtctcgt cgataatatc gatatattgg acgatagtca 1320
aaccgggaga tatattatta ataaattcga cgggaaattt aatagcgccg cgtggatatt 1380
ttaaattaca atcgggaaaa tcgtcgataa tgcgttcgga tgcgccgata ggaatatgta 1440
attcggaatg tataacgccg aatggatcga taccgaatga taaaccgttt caaaatgtca 1500
atcgtataac ctatggagcg tgtccgcgtt atgtcaaaca aaatacgtta aaattagcga 1560
cgggaatgcg taatgtcccg gaaaaacaaa cgcgtggaat atttggagcg atagcgggat 1620
ttatagaaaa tggatgggaa ggaatggtcg atggatggta tggatttcgt catcaaaatt 1680
cggaaggaac gggacaagcg gcggatttaa aatcgacgcg tgcggcgata aatcaaataa 1740
cgggaaaatt aaatcgtgtc ataaaaaaaa cgaatgaaaa atttcatcaa atagaaaaag 1800
aattttcgga agtcgaagga cgtatacaag atttagaaaa atatgtcgaa gatacgaaaa 1860
tagatttatg gtcgtataat gcggaattat tagtcgcgtt agaaaatcaa catacgatag 1920
atttaacgga ttcggaaatg aataaattat ttgaacgtac gcgtaaacaa ttacgtgaaa 1980
atgcggaaga tatgggaaat ggatgtttta aaatatatca taaatgtgat aatgcgtgta 2040
taggatcgat acgtaatgga acgtatgatc atgatgtcta tcgtgatgaa gcgttaaata 2100
atcgttttca aataaaagga gtccaattaa aatcgggata taaagattgg atattatgga 2160
tatcgtttgc gatatcgtgc tttttgcttt gtgttgttct gctggggttc attatgtggg 2220
cctgccaaaa aggcaacatt aggtgcaaca tttgcatttg agtgcattaa ttaaaaacac 2280
ccttgtttct actaataacc cggcggccca aaatgccgac tcggagcgaa agatatacct 2340
cccccggggc cgggaggtcg cgtcaccgac cacgccgccg gcccaggcga cgcgcgacac 2400
ggacacctgt ccccaaaaac gccaccatcg cagccacaca cggagcgccc ggggccctct 2460
ggtcaacccc aggacacacg cgggagcagc gccgggccgg ggacgccctc ccggcggtca 2520
cctaaatgct agagctcgct gatcagcctc gactgtgcct tctagttgcc agccatctgt 2580
tgtttgcccc tcccccgtgc cttccttgac cctggaaggt gccactccca ctgtcctttc 2640
ctaataaaat gaggaaattg catcgcattg tctgagtagg tgtcattcta ttctgggggg 2700
tggggtgggg caggacagca agggggagga ttgggaagac aatagcaggc atgctgggga 2760
tgcggtgggc tctatggctt ctgaggcgga aagaaccagc tgcattaatg aatcggccaa 2820
cgcgcgggga gaggcggttt gcgtattggg cgctcttccg cttgatgacc tctagctaga 2880
gcttggcgta atcatggtca tagctgtttc ctgtgtgaaa ttgttatccg ctcacaattc 2940
cacacaacat acgagccgga agcataaagt gtaaagcctg gggtgcctaa tgagtgagct 3000
aactcacatt aattgcgttg cgctcactgc ccgctttcca gtcgggaaac ctgtcgtgcc 3060
agctgcatta atgaatcggc caacgcgcgg ggagaggcgg tttgcgtatt gggcgctctt 3120
ccgcttcctc gctcactgac tcgctgcgct cggtcgttcg gctgcggcga gcggtatcag 3180
ctcactcaaa ggcggtaata cggttatcca cagaatcagg ggataacgca ggaaagaaca 3240
tgtgagcaaa aggccagcaa aaggccagga accgtaaaaa ggccgcgttg ctggcgtttt 3300
tccataggct ccgcccccct gacgagcatc acaaaaatcg acgctcaagt cagaggtggc 3360
gaaacccgac aggactataa agataccagg cgtttccccc tggaagctcc ctcgtgcgct 3420
ctcctgttcc gaccctgccg cttaccggat acctgtccgc ctttctccct tcgggaagcg 3480
tggcgctttc tcatagctca cgctgtaggt atctcagttc ggtgtaggtc gttcgctcca 3540
agctgggctg tgtgcacgaa ccccccgttc agcccgaccg ctgcgcctta tccggtaact 3600
atcgtcttga gtccaacccg gtaagacacg acttatcgcc actggcagca gccactggta 3660
acaggattag cagagcgagg tatgtaggcg gtgctacaga gttcttgaag tggtggccta 3720
actacggcta cactagaaga acagtatttg gtatctgcgc tctgctgaag ccagttacct 3780
tcggaaaaag agttggtagc tcttgatccg gcaaacaaac caccgctggt agcggtggtt 3840
tttttgtttg caagcagcag attacgcgca gaaaaaaagg atctcaagaa gatcctttga 3900
tcttttctac ggggtctgac gctcagtgga acgaaaactc acgttaaggg attttggtca 3960
tgagattatc aaaaaggatc ttcacctaga tccttttaaa ttaaaaatga agttttaaat 4020
caatctaaag tatatatgag taaacttggt ctgacagtta ccaatgctta atcagtgagg 4080
cacctatctc agcgatctgt ctatttcgtt catccatagt tgcctgactc cccgtcgtgt 4140
agataactac gatacgggag ggcttaccat ctggccccag tgctgcaatg ataccgcgag 4200
acccacgctc accggctcca gatttatcag caataaacca gccagccgga agggccgagc 4260
gcagaagtgg tcctgcaact ttatccgcct ccatccagtc tattaattgt tgccgggaag 4320
ctagagtaag tagttcgcca gttaatagtt tgcgcaacgt tgttgccatt gctacaggca 4380
tcgtggtgtc acgctcgtcg tttggtatgg cttcattcag ctccggttcc caacgatcaa 4440
ggcgagttac atgatccccc atgttgtgca aaaaagcggt tagctccttc ggtcctccga 4500
tcgttgtcag aagtaagttg gccgcagtgt tatcactcat ggttatggca gcactgcata 4560
attctcttac tgtcatgcca tccgtaagat gcttttctgt gactggtgag tactcaacca 4620
agtcattctg agaatagtgt atgcggcgac cgagttgctc ttgcccggcg tcaatacggg 4680
ataataccgc gccacatagc agaactttaa aagtgctcat cattggaaaa cgttcttcgg 4740
ggcgaaaact ctcaaggatc ttaccgctgt tgagatccag ttcgatgtaa cccactcgtg 4800
cacccaactg atcttcagca tcttttactt tcaccagcgt ttctgggtga gcaaaaacag 4860
gaaggcaaaa tgccgcaaaa aagggaataa gggcgacacg gaaatgttga atactcatac 4920
tcttcctttt tcaatattat tgaagcattt atcagggtta ttgtctcatg agcggataca 4980
tatttgaatg tatttagaaa aa 5002
<210> 114
<211> 4705
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-H3N2-NA-DO
<400> 114
tccgcgcaca tttccccgaa aagtgccacc tgacgtcatc gccacctgac gtcgatatgc 60
caagtacgcc ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt 120
acatgacctt atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta 180
ccatggtgat gcggttttgg cagtacatca atgggcgtgg atagcggttt gactcacggg 240
gatttccaag tctccacccc attgacgtca atgggagttt gttttggcac caaaatcaac 300
gggactttcc aaaatgtcgt aacaactccg ccccattgac gcaaatgggc ggtaggcgtg 360
tacggtggga ggtctatata agcagagctc tctggctaac tagagaaccc actgcttact 420
ggcttatcga aattaatacg actcactata gggagaccca agctgttaac gctagcagtt 480
aaccggagta ctggtcgacc tccgaagttg ggggggagca aaagcaggag taaagatgaa 540
tccaaatcaa aagataataa caattggctc tgtttctctc ctcattgcca caatatgctt 600
ccttatgcaa attgccatcc tggtaactac tgtaacattg catttcaaac aacatgattg 660
taattcgtcg ccgaataatc aagtcatgtt atgtgaaccg acgataatag aacgtaatac 720
gacggaaata gtctatttaa cgaatataac gatagaaaaa gaaatatgtc cgaaattagc 780
ggaatatcgt aattggtcga aaccgcaatg taatataacg ggatttgcgc cgttttcgaa 840
agataattcg atacgtttat cggcgggagg agatatatgg gtcacgcgtg aaccgtatgt 900
ctcgtgtgat ccggataaat gttatcaatt tgcgttagga caaggaacga cgttaaataa 960
tggacattcg aatgatacgg tccatgatcg tacgccgtat cgcacgttat taatgaatga 1020
attaggagtc ccgtttcatt taggaacgcg tcaagtctgt atagcgtggt cgtcgtcgtc 1080
gtgtcatgat ggaaaagcgt ggttacatgt ctgtataacg ggagatgata aaaatgcgac 1140
ggcgtcgttt atatataatg gacgtttagt cgattcgata ggatcgtggt cgaaaaatat 1200
attacgtacg caagaatcgg aatgtgtctg tataaatgga acgtgtacgg tcgtcatgac 1260
ggatggatcg gcgtcgggaa aagcggatac gaaagtctta tttatagaag aaggaaaaat 1320
agtccatata tcgacgttat cgggatcggc gcaacatgtc gaagaatgtt cgtgttatcc 1380
gcgttatccg ggagtccgtt gtgtctgtcg tgataattgg aaaggatcga atcgtccgat 1440
agtcgatata aatgtcaaag attattcgat agtctcgtcg tatgtctgtt cgggattagt 1500
cggagatacg ccgcgtaaaa atgatcgttt ttcgtcgtcg cattgtcaag atccgaataa 1560
tgaagaagga ggacatggag tcaaaggatg ggcgtttgat gatggaaatg atgtctggat 1620
gggacgtacg ataaatgaaa aattacgttc gggatatgaa acgtttaaag tcatagaagg 1680
atggtcgaaa ccgaattcga aattacaaac gaatcgtcaa gtcatagtcg aacgtggaaa 1740
tcgttcggga tattcgggaa tattttcggt cgaaggaaaa tcgtgtataa atcgttgttt 1800
ttatgtcgaa ttaatacgtg gacgtaaaga agaaactaaa gtctggtgga cctcaaacag 1860
tattgttgtg ctttgtggca cctcaggtac atatggaaca ggctcatggc ctgatggggc 1920
ggatatcaat ctcatgccta tataactttc gcaattttag aaaaaactcc ttgtttctac 1980
taataacccg gcggcccaaa atgccgactc ggagcgaaag atatacctcc cccggggccg 2040
ggaggtcgcg tcaccgacca cgccgccggc ccaggcgacg cgcgacacgg acacctgtcc 2100
ccaaaaacgc caccatcgca gccacacacg gagcgcccgg ggccctctgg tcaaccccag 2160
gacacacgcg ggagcagcgc cgggccgggg acgccctccc ggcggtcacc taaatgctag 2220
agctcgctga tcagcctcga ctgtgccttc tagttgccag ccatctgttg tttgcccctc 2280
ccccgtgcct tccttgaccc tggaaggtgc cactcccact gtcctttcct aataaaatga 2340
ggaaattgca tcgcattgtc tgagtaggtg tcattctatt ctggggggtg gggtggggca 2400
ggacagcaag ggggaggatt gggaagacaa tagcaggcat gctggggatg cggtgggctc 2460
tatggcttct gaggcggaaa gaaccagctg cattaatgaa tcggccaacg cgcggggaga 2520
ggcggtttgc gtattgggcg ctcttccgct tgatgacctc tagctagagc ttggcgtaat 2580
catggtcata gctgtttcct gtgtgaaatt gttatccgct cacaattcca cacaacatac 2640
gagccggaag cataaagtgt aaagcctggg gtgcctaatg agtgagctaa ctcacattaa 2700
ttgcgttgcg ctcactgccc gctttccagt cgggaaacct gtcgtgccag ctgcattaat 2760
gaatcggcca acgcgcgggg agaggcggtt tgcgtattgg gcgctcttcc gcttcctcgc 2820
tcactgactc gctgcgctcg gtcgttcggc tgcggcgagc ggtatcagct cactcaaagg 2880
cggtaatacg gttatccaca gaatcagggg ataacgcagg aaagaacatg tgagcaaaag 2940
gccagcaaaa ggccaggaac cgtaaaaagg ccgcgttgct ggcgtttttc cataggctcc 3000
gcccccctga cgagcatcac aaaaatcgac gctcaagtca gaggtggcga aacccgacag 3060
gactataaag ataccaggcg tttccccctg gaagctccct cgtgcgctct cctgttccga 3120
ccctgccgct taccggatac ctgtccgcct ttctcccttc gggaagcgtg gcgctttctc 3180
atagctcacg ctgtaggtat ctcagttcgg tgtaggtcgt tcgctccaag ctgggctgtg 3240
tgcacgaacc ccccgttcag cccgaccgct gcgccttatc cggtaactat cgtcttgagt 3300
ccaacccggt aagacacgac ttatcgccac tggcagcagc cactggtaac aggattagca 3360
gagcgaggta tgtaggcggt gctacagagt tcttgaagtg gtggcctaac tacggctaca 3420
ctagaagaac agtatttggt atctgcgctc tgctgaagcc agttaccttc ggaaaaagag 3480
ttggtagctc ttgatccggc aaacaaacca ccgctggtag cggtggtttt tttgtttgca 3540
agcagcagat tacgcgcaga aaaaaaggat ctcaagaaga tcctttgatc ttttctacgg 3600
ggtctgacgc tcagtggaac gaaaactcac gttaagggat tttggtcatg agattatcaa 3660
aaaggatctt cacctagatc cttttaaatt aaaaatgaag ttttaaatca atctaaagta 3720
tatatgagta aacttggtct gacagttacc aatgcttaat cagtgaggca cctatctcag 3780
cgatctgtct atttcgttca tccatagttg cctgactccc cgtcgtgtag ataactacga 3840
tacgggaggg cttaccatct ggccccagtg ctgcaatgat accgcgagac ccacgctcac 3900
cggctccaga tttatcagca ataaaccagc cagccggaag ggccgagcgc agaagtggtc 3960
ctgcaacttt atccgcctcc atccagtcta ttaattgttg ccgggaagct agagtaagta 4020
gttcgccagt taatagtttg cgcaacgttg ttgccattgc tacaggcatc gtggtgtcac 4080
gctcgtcgtt tggtatggct tcattcagct ccggttccca acgatcaagg cgagttacat 4140
gatcccccat gttgtgcaaa aaagcggtta gctccttcgg tcctccgatc gttgtcagaa 4200
gtaagttggc cgcagtgtta tcactcatgg ttatggcagc actgcataat tctcttactg 4260
tcatgccatc cgtaagatgc ttttctgtga ctggtgagta ctcaaccaag tcattctgag 4320
aatagtgtat gcggcgaccg agttgctctt gcccggcgtc aatacgggat aataccgcgc 4380
cacatagcag aactttaaaa gtgctcatca ttggaaaacg ttcttcgggg cgaaaactct 4440
caaggatctt accgctgttg agatccagtt cgatgtaacc cactcgtgca cccaactgat 4500
cttcagcatc ttttactttc accagcgttt ctgggtgagc aaaaacagga aggcaaaatg 4560
ccgcaaaaaa gggaataagg gcgacacgga aatgttgaat actcatactc ttcctttttc 4620
aatattattg aagcatttat cagggttatt gtctcatgag cggatacata tttgaatgta 4680
tttagaaaaa taaacaaata ggggt 4705
<210> 115
<211> 5022
<212> DNA
<213> 人工序列
<220>
<223> pHW2000-HA-DO (H1-H3嵌合体)
<400> 115
acctgacgtc gatatgccaa gtacgccccc tattgacgtc aatgacggta aatggcccgc 60
ctggcattat gcccagtaca tgaccttatg ggactttcct acttggcagt acatctacgt 120
attagtcatc gctattacca tggtgatgcg gttttggcag tacatcaatg ggcgtggata 180
gcggtttgac tcacggggat ttccaagtct ccaccccatt gacgtcaatg ggagtttgtt 240
ttggcaccaa aatcaacggg actttccaaa atgtcgtaac aactccgccc cattgacgca 300
aatgggcggt aggcgtgtac ggtgggaggt ctatataagc agagctctct ggctaactag 360
agaacccact gcttactggc ttatcgaaat taatacgact cactataggg agacccaagc 420
tgttaacgct agcagttaac cggagtactg gtcgacctcc gaagttgggg gggagcaaaa 480
gcaggggaaa aataaaagca accaaaatga aagtaaaact aatggttctg ttatgtacat 540
ttacagctac atatgcacaa aaacttcccg gaagtgacaa cagcatggca acgctgtgct 600
taggacatca tgcggtcccg aatggaacgt tagtcaaaac gataacggat gatcaaatag 660
aagtcacgaa tgcgacggaa ttagtccaat cgtcgtcgac gggacgtata tgtaattcgc 720
cgcatcaaat attagatgga aaaaattgta cgttaataga tgcgttatta ggagatccgc 780
attgtgatga ttttcaaaat aaagaatggg atttatttgt cgaacgttcg acggcgtatt 840
cgaattgtta tccgtattat gtcccggatt atgcgtcgtt acgttcgtta gtcgcgtcgt 900
cgggaacgtt agaatttacg caagaatcgt ttaattggac gggagtcgcg caagatggat 960
cgtcgtatgc gtgtcgtcgt gaatcggtca attcgttttt ttcgcgttta aattggttac 1020
ataaattaga ttataaatat ccggcgttaa aagtcacgat gccgaataat gataaatttg 1080
ataaattata tatatgggga gtccatcatc cgggaacgga tcgtgatcaa acgaatttat 1140
atgtccaaac gtcgggacgt gtcacggtct cgacgaaacg ttcgcaacaa acggtcatac 1200
cgaatatagg atcgcgtccg tgggtccgtg gagtctcgtc gataatatcg atatattgga 1260
cgatagtcaa accgggagat atattattaa taaattcgac gggaaattta atagcgccgc 1320
gtggatattt taaattacaa tcgggaaaat cgtcgataat gcgttcggat gcgccgatag 1380
gaatatgtaa ttcggaatgt ataacgccga atggatcgat accgaatgat aaaccgtttc 1440
aaaatgtcaa tcgtataacc tatggagcgt gtccgcgtta tgtcaaacaa aatacgttaa 1500
aattagcgac gggaatgcgt aatgtcccgg aaaaacaaac gcgtggaata tttggagcga 1560
tagcgggatt tatagaaaat ggatgggaag gaatggtcga tggatggtat ggatttcgtc 1620
atcaaaattc ggaaggaacg ggacaagcgg cggatttaaa atcgacgcgt gcggcgataa 1680
atcaaataac gggaaaatta aatcgtgtca taaaaaaaac gaatgaaaaa tttcatcaaa 1740
tagaaaaaga attttcggaa gtcgaaggac gtatacaaga tttagaaaaa tatgtcgaag 1800
atacgaaaat agatttatgg tcgtataatg cggaattatt agtcgcgtta gaaaatcaac 1860
atacgataga tttaacggat tcggaaatga ataaattatt tgaacgtacg cgtaaacaat 1920
tacgtgaaaa tgcggaagat atgggaaatg gatgttttaa aatatatcat aaatgtgata 1980
atgcgtgtat aggatcgata cgtaatggaa cgtatgatca tgatgtctat cgtgatgaag 2040
cgttaaataa tcgttttcaa ataaaaggag tccaattaaa atcgggatat aaagatatct 2100
tagcgatata ttcgacggtc gcgtcgtccc tagttctttt agtctccctg ggggcaatca 2160
gcttctggat gtgttccaat gggtctttac agtgtagaat atgcatctaa gaccagaatt 2220
tcagaaatat aaggaaaaac acccttgttt ctactaataa cccggcggcc caaaatgccg 2280
actcggagcg aaagatatac ctcccccggg gccgggaggt cgcgtcaccg accacgccgc 2340
cggcccaggc gacgcgcgac acggacacct gtccccaaaa acgccaccat cgcagccaca 2400
cacggagcgc ccggggccct ctggtcaacc ccaggacaca cgcgggagca gcgccgggcc 2460
ggggacgccc tcccggcggt cacctaaatg ctagagctcg ctgatcagcc tcgactgtgc 2520
cttctagttg ccagccatct gttgtttgcc cctcccccgt gccttccttg accctggaag 2580
gtgccactcc cactgtcctt tcctaataaa atgaggaaat tgcatcgcat tgtctgagta 2640
ggtgtcattc tattctgggg ggtggggtgg ggcaggacag caagggggag gattgggaag 2700
acaatagcag gcatgctggg gatgcggtgg gctctatggc ttctgaggcg gaaagaacca 2760
gctgcattaa tgaatcggcc aacgcgcggg gagaggcggt ttgcgtattg ggcgctcttc 2820
cgcttgatga cctctagcta gagcttggcg taatcatggt catagctgtt tcctgtgtga 2880
aattgttatc cgctcacaat tccacacaac atacgagccg gaagcataaa gtgtaaagcc 2940
tggggtgcct aatgagtgag ctaactcaca ttaattgcgt tgcgctcact gcccgctttc 3000
cagtcgggaa acctgtcgtg ccagctgcat taatgaatcg gccaacgcgc ggggagaggc 3060
ggtttgcgta ttgggcgctc ttccgcttcc tcgctcactg actcgctgcg ctcggtcgtt 3120
cggctgcggc gagcggtatc agctcactca aaggcggtaa tacggttatc cacagaatca 3180
ggggataacg caggaaagaa catgtgagca aaaggccagc aaaaggccag gaaccgtaaa 3240
aaggccgcgt tgctggcgtt tttccatagg ctccgccccc ctgacgagca tcacaaaaat 3300
cgacgctcaa gtcagaggtg gcgaaacccg acaggactat aaagatacca ggcgtttccc 3360
cctggaagct ccctcgtgcg ctctcctgtt ccgaccctgc cgcttaccgg atacctgtcc 3420
gcctttctcc cttcgggaag cgtggcgctt tctcatagct cacgctgtag gtatctcagt 3480
tcggtgtagg tcgttcgctc caagctgggc tgtgtgcacg aaccccccgt tcagcccgac 3540
cgctgcgcct tatccggtaa ctatcgtctt gagtccaacc cggtaagaca cgacttatcg 3600
ccactggcag cagccactgg taacaggatt agcagagcga ggtatgtagg cggtgctaca 3660
gagttcttga agtggtggcc taactacggc tacactagaa gaacagtatt tggtatctgc 3720
gctctgctga agccagttac cttcggaaaa agagttggta gctcttgatc cggcaaacaa 3780
accaccgctg gtagcggtgg tttttttgtt tgcaagcagc agattacgcg cagaaaaaaa 3840
ggatctcaag aagatccttt gatcttttct acggggtctg acgctcagtg gaacgaaaac 3900
tcacgttaag ggattttggt catgagatta tcaaaaagga tcttcaccta gatcctttta 3960
aattaaaaat gaagttttaa atcaatctaa agtatatatg agtaaacttg gtctgacagt 4020
taccaatgct taatcagtga ggcacctatc tcagcgatct gtctatttcg ttcatccata 4080
gttgcctgac tccccgtcgt gtagataact acgatacggg agggcttacc atctggcccc 4140
agtgctgcaa tgataccgcg agacccacgc tcaccggctc cagatttatc agcaataaac 4200
cagccagccg gaagggccga gcgcagaagt ggtcctgcaa ctttatccgc ctccatccag 4260
tctattaatt gttgccggga agctagagta agtagttcgc cagttaatag tttgcgcaac 4320
gttgttgcca ttgctacagg catcgtggtg tcacgctcgt cgtttggtat ggcttcattc 4380
agctccggtt cccaacgatc aaggcgagtt acatgatccc ccatgttgtg caaaaaagcg 4440
gttagctcct tcggtcctcc gatcgttgtc agaagtaagt tggccgcagt gttatcactc 4500
atggttatgg cagcactgca taattctctt actgtcatgc catccgtaag atgcttttct 4560
gtgactggtg agtactcaac caagtcattc tgagaatagt gtatgcggcg accgagttgc 4620
tcttgcccgg cgtcaatacg ggataatacc gcgccacata gcagaacttt aaaagtgctc 4680
atcattggaa aacgttcttc ggggcgaaaa ctctcaagga tcttaccgct gttgagatcc 4740
agttcgatgt aacccactcg tgcacccaac tgatcttcag catcttttac tttcaccagc 4800
gtttctgggt gagcaaaaac aggaaggcaa aatgccgcaa aaaagggaat aagggcgaca 4860
cggaaatgtt gaatactcat actcttcctt tttcaatatt attgaagcat ttatcagggt 4920
tattgtctca tgagcggata catatttgaa tgtatttaga aaaataaaca aataggggtt 4980
ccgcgcacat ttccccgaaa agtgccacct gacgtcatcg cc 5022
<210> 116
<211> 51
<212> DNA
<213> 人工序列
<220>
<223> pHW2000 5' 克隆位点 (BsmBI) 序列
<400> 116
tccgaagttg ggggggagga gacggtaccg tctccaataa cccggcggcc c 51
<210> 117
<211> 51
<212> DNA
<213> 人工序列
<220>
<223> pHW2000 3' 克隆位点 (BsmBI) 序列
<400> 117
gggccgccgg gttattggag acggtaccgt ctcctccccc ccaacttcgg a 51

Claims (28)

1.疫苗，其包含在药学上或在兽医学上可接受的载料、稀释剂或赋形剂和有效量的减毒猪流感病毒(SIV)，其中所述SIV包含：
(a)由SEQ ID NO：93组成的HA基因区段，和由SEQ ID NO：94组成的NA基因区段；或者
(b)由SEQ ID NO：93组成的HA基因区段，由SEQ ID NO：94组成的NA基因区段，和包含SEQ ID NO：90中所示的序列的NS1基因区段；或者
(c)由SEQ ID NO：105组成的HA基因区段，和由SEQ ID NO：96组成的NA基因区段；或者
(d)由SEQ ID NO：105组成的HA基因区段，由SEQ ID NO：96组成的NA基因区段，和包含SEQ ID NO：90中所示的序列的NS1基因区段；或者
(e)包含SEQ ID NO：91中所示的序列的HA基因区段，和由SEQ ID NO：92组成的NA基因区段；或者
(f)由SEQ ID NO：91组成的HA基因区段，由SEQ ID NO：92组成的NA基因区段，和由SEQID NO：90组成的NS1基因区段。
2.权利要求1的疫苗，其中所述SIV包含(a)。
3.权利要求1的疫苗，其中所述SIV包含(b)。
4.权利要求1的疫苗，其中所述SIV包含(c)。
5.权利要求1的疫苗，其中所述SIV包含(d)。
6.权利要求1的疫苗，其中所述SIV包含(e)。
7.权利要求1的疫苗，其中所述SIV包含(f)。
8.权利要求1的疫苗，其中在(a)、(c)或(e)的情况下，所述SIV进一步包含：
由SEQ ID NO：83组成的NS基因区段，
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
9.权利要求1的疫苗，
其中在(a)、(c)或(e)的情况下，所述SIV进一步包含：
由SEQ ID NO：83组成的NS基因区段，
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段；或者
其中所述SIV包含：
SIV H1N2变体，其中
血凝素(HA)基因编码序列被密码子去优化为SEQ ID NO：29，且
神经氨酸酶(NA)基因编码序列被密码子去优化为SEQ ID NO：32；
SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，且
NA基因编码序列被密码子去优化为SEQ ID NO：38；或
SIV H1N1变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：22，且
NA基因编码序列被密码子去优化为SEQ ID NO：25。
10.权利要求2的疫苗，其中所述SIV进一步包含：
由SEQ ID NO：83组成的NS基因区段，
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
11.权利要求4的疫苗，其中所述SIV进一步包含：
由SEQ ID NO：83组成的NS基因区段，
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
12.权利要求6的疫苗，其中所述SIV进一步包含：
由SEQ ID NO：83组成的NS基因区段，
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
13.权利要求1的疫苗，其中在(b)、(d)或(f)的情况下，所述SIV进一步包含：
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
14.权利要求1的疫苗，
其中在(b)、(d)或(f)的情况下，所述SIV进一步包含：
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段；或者
其中所述SIV包含：
SIV H1N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：29，
NA基因编码序列被密码子去优化为SEQ ID NO：32，且
非结构蛋白(NS)基因编码序列被密码子去优化为SEQ ID NO：27；
SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，
NA基因编码序列被密码子去优化为SEQ ID NO：38，且
NS基因编码序列被密码子去优化为SEQ ID NO：27；或
SIV H1N1变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：22，
NA基因编码序列被密码子去优化为SEQ ID NO：25，且
NS基因编码序列被密码子去优化为SEQ ID NO：27。
15.权利要求3的疫苗，其中所述SIV进一步包含：
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
16.权利要求5的疫苗，其中所述SIV进一步包含：
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
17.权利要求7的疫苗，其中所述SIV进一步包含：
由SEQ ID NO：82组成的M基因区段，
由SEQ ID NO：81组成的NP基因区段，
由SEQ ID NO：80组成的PA基因区段，
由SEQ ID NO：79组成的PB1基因区段，和
由SEQ ID NO：78组成的PB2基因区段。
18.权利要求1的疫苗，其进一步包含至少一种另外的与除了猪流感之外的其他猪病原体相关或者源自除了猪流感之外的其他猪病原体的抗原。
19.权利要求18的疫苗，其中所述至少一种或多种另外的抗原能够在猪中引发针对猪肺炎枝原体(M.hyo)、猪圆环病毒2(PCV2)或猪呼吸和生殖综合征病毒(PRRSV)的免疫应答。
20.权利要求1的疫苗，其进一步包含佐剂。
21.权利要求19的疫苗，其进一步包含佐剂。
22.权利要求1～21中任一项的疫苗在制备用于预防或治疗猪流感的药剂中的用途。
23.权利要求1～21中任一项的疫苗在制备用于对猪动物进行疫苗接种的药剂中的用途。
24.权利要求23的用途，其中所述猪动物为产仔前3周至6周的母猪。
25.权利要求1的疫苗，其中所述SIV包含：
(i)(1)(e)或(f)，和(2)(c)或(d)；或者
(ii)(1)(a)或(b)，和(2)(c)或(d)；或者
(iii)(1)(e)或(f)，和(2)(c)或(d)，和(3)(a)或(b)；或者
(iv)
(1)SIV H1N1变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：22，且
NA基因编码序列被密码子去优化为SEQ ID NO：25；或
SIV H1N1变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：22，
NA基因编码序列被密码子去优化为SEQ ID NO：25，且
NS基因编码序列被密码子去优化为SEQ ID NO：27，和
(2)SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，且
NA基因编码序列被密码子去优化为SEQ ID NO：38；或
SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，
NA基因编码序列被密码子去优化为SEQ ID NO：38，且
NS基因编码序列被密码子去优化为SEQ ID NO：27；或者
(v)
(1)SIV H1N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：29，且
NA基因编码序列被密码子去优化为SEQ ID NO：32；或
SIV H1N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：29，
NA基因编码序列被密码子去优化为SEQ ID NO：32，且
NS基因编码序列被密码子去优化为SEQ ID NO：27，和
(2)SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，且
NA基因编码序列被密码子去优化为SEQ ID NO：38；或
SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，
NA基因编码序列被密码子去优化为SEQ ID NO：38，且
NS基因编码序列被密码子去优化为SEQ ID NO：27；或者
(vi)
(1)SIV H1N1变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：22，且
NA基因编码序列被密码子去优化为SEQ ID NO：25；或
SIV H1N1变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：22，
NA基因编码序列被密码子去优化为SEQ ID NO：25，且
NS基因编码序列被密码子去优化为SEQ ID NO：27，
(2)SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，且
NA基因编码序列被密码子去优化为SEQ ID NO：38；或
SIV H3N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：35，
NA基因编码序列被密码子去优化为SEQ ID NO：38，且
NS基因编码序列被密码子去优化为SEQ ID NO：27，和
(3)SIV H1N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：29，且
NA基因编码序列被密码子去优化为SEQ ID NO：32；或
SIV H1N2变体，其中
HA基因编码序列被密码子去优化为SEQ ID NO：29，
NA基因编码序列被密码子去优化为SEQ ID NO：32，且
NS基因编码序列被密码子去优化为SEQ ID NO：27。
26.用于产生权利要求1～21中任一项的疫苗的组合物，其包含：
(A)载体，其包含(i)可操作地连接至启动子的HA基因区段，和(ii)可操作地连接至启动子的NA基因区段；或者
(B)载体，其包含(i)可操作地连接至启动子的HA基因区段，(ii)可操作地连接至启动子的NA基因区段，(iii)可操作地连接至启动子的NS基因区段，(iv)可操作地连接至启动子的M基因区段，(v)可操作地连接至启动子的NP基因区段，(vi)可操作地连接至启动子的PA基因区段，(vii)可操作地连接至启动子的PB1基因区段，和(viii)可操作地连接至启动子的PB2基因区段；或者
(C)载体，其包含(i)可操作地连接至启动子的HA基因区段，(ii)可操作地连接至启动子的NA基因区段，和(iii)可操作地连接至启动子的NS基因区段。
27.制备减毒猪流感病毒(SIV)疫苗株的方法，其包括使细胞与对于产生重排列的、减毒的、感染性的流感病毒颗粒来说有效的量的权利要求26的组合物相接触。
28.包含权利要求26的组合物的分离的细胞。
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