新型发热伴血小板减少综合征病毒

摘要

本发明涉及新型基因型发热伴血小板减少综合征病毒及其免疫原性组合物的用途，本发明的病毒中的发热伴血小板减少综合征病毒与以往的血小板减少综合征病毒具有遗传性区别，是在系统学上从B基因型细化为三个的新型病毒，因此，在仅通过某个特定基因型的病毒产生限制性防御能力的疫苗的特性上，可将本发明的新型病毒有用地利用为针对发热伴血小板减少综合征病毒具有优秀的交叉免疫原性的疫苗。

说明书

技术领域

本发明涉及新型基因型发热伴血小板减少综合征病毒及其免疫原性组合物的用途。

背景技术

发热伴血小板减少综合征(Severe fever with thrombocytopenia syndrome，SFTS)是一种伴随着如高烧、呕吐、腹泻、血小板减少、白细胞减少及多发性器官功能衰竭等症状，死亡率高达6～30％的严重的疾病(Yu XJ et al.，N.Engl.J.Med.2011；364:1523-32；Ding F et al Clin Infect Dis 2013；56:1682-3)。

发热伴血小板减少综合征的原因病原体为发热伴血小板减少综合征病毒(severefever thrombocytopenia syndrome virus，SFTSV)，属于布尼亚病毒科(Bunyaviridae)。布尼亚病毒科为包含三个节段的负链(negative-strand)RNA病毒，由包括正布尼病毒(Orthobunyavirus)，汉他病毒(Hantavirus)，内罗病毒(Nairovirus)，白蛉病毒(Phlebovirus)，番茄斑萎病毒(Tospovirus)的五个属(genus)形成。发热伴血小板减少综合征病毒属于白蛉病毒属(Phlebovirus genus)，裂谷热病毒(Rift valley fever virus)等就属于这种病毒属中。2011年在中国首次报道过发热伴血小板减少综合征病毒(Yu XJet al.ibid)，这种病毒为在除了中国之外的韩国和日本持续发病的新变种病毒。发热伴血小板减少综合征病毒为直径为80～100nm的球形病毒。此病毒具有作为单链负股RNA节段(single-stranded negative sense RNA segment)的大节段(large(L)segment)、中节段(medium(M)segment)及小节段(small(S)segment；NP，NS)等三个基因。

发热伴血小板减少综合征病毒以长角血蜱(Haemaphysalis longicornis)作为媒介，上述蜱也遍布于韩国(Chae JS et al.J Vet Sci 2008；9:285-93；Kim CM et al.ApplEnviron Microbiol 2006；72:5766-76)。发热伴血小板减少综合征病毒的血清转换及病毒血症被发现于山羊、羊、猪及狗等饲养动物中，而这种动物也在发热伴血小板减少综合征病毒分布的地区中作用为中间媒介(Zhao L et al.Emerg Infect Dis 2013；18:963-5；NiuG et al.Emerg Infect Dis 2013；19:756-63)。在患者的血液中检测到发热伴血小板减少综合征病毒，尤其在重症患者的血液中的发热伴血小板减少综合征病毒的浓度非常高，因此，人与人之间可通过血液传播(Tang X，Wu W，Wang H，et al.J Infect Dis 2013；207:736-739.)。

由于尚未开发出针对发热伴血小板减少综合征病毒的抗病毒剂，对于发热伴血小板减少综合征的治疗，主要使用输血、肾替代疗法等针对器官功能衰竭的保守疗法。在中国，从2012年开始将利巴韦林静脉注射导入了治疗方针上，在最近发表的治疗结果中，利巴韦林给药组和非给药组之间的死亡率并不存在差异。因此，需要针对发热伴血小板减少综合征病毒的疫苗，但至今还未开发出疫苗。

发明内容

技术问题

本发明的目的在于，提供新型基因型发热伴血小板减少综合征病毒及利用其的免疫原性组合物。

技术方案

为了实现上述目的，本发明提供新型发热伴血小板减少综合征病毒。

并且，本发明提供用于预防或治疗发热伴血小板减少综合征的免疫原性组合物。

并且，本发明提供针对发热伴血小板减少综合征病毒或其抗原的抗体。

并且，本发明提供发热伴血小板减少综合征病毒的诊断试剂盒。

并且，本发明提供发热伴血小板减少综合征病毒抗体的检测方法。

并且，本发明提供生产针对发热伴血小板减少综合征病毒的抗血清的方法。

同时，本发明提供与发热伴血小板减少综合征的诊断有关的信息的提供方法。

有益效果

本发明的发热伴血小板减少综合征病毒与以往的血小板减少综合征病毒具有遗传性区别，是在系统学上从B基因型细化的新型病毒，因此，在仅通过某个特定基因型的病毒产生限制性防御能力的疫苗的特性上，可将本发明的新型病毒有用地利用为针对发热伴血小板减少综合征病毒具有优秀的交叉免疫原性的疫苗。

附图说明

图1为示出本发明的三种新型病毒和在本发明的三种新型病毒分离的发热伴血小板减少综合征病毒L基因的系统树图的图。

图2为示出本发明的三种新型病毒和在本发明的三种新型病毒分离的发热伴血小板减少综合征病毒M基因的系统树图的图。

图3为示出本发明的三种新型病毒和在本发明的三种新型病毒分离的发热伴血小板减少综合征病毒S(NP)基因的系统树图的图。

图4为示出本发明的三种新型病毒和在本发明的三种新型病毒分离的发热伴血小板减少综合征病毒S(NS)基因的系统树图的图。

图5为示出本发明的B-1(CB3/2016)、B-2(CB7/2017)及B-3(CB6/2016)基因型的三种新型病毒的L基因及M基因中的氨基酸变异部位的图。

图6为确认本发明的B-1(CB3/2016)、B-2(CB7/2017)及B-3(CB6/2016)基因型的三种新型病毒的疫苗效果的图。

最优实施方式

以下，参照附图通过本发明的实例更加详细地说明。但是，以下实例为了例示本发明而揭示，当本领域的普通技术人员判断主旨显要的描述或对结构的具体说明不必要地混淆本发明的要旨时，可省略其详细说明，而本发明并不限定于此。本发明在发明要求保护范围的记载及由此解释的同等范畴内可进行多种变形及应用。

并且，在本说明书中所使用的术语(terminology)是为了适当表述本发明的优选实施例而使用的术语，其可根据使用人员、操作人员的意图或本发明所属技术领域的惯例等而不同。因此，应以本说明书整个内容为基础对本术语下定义。在整个说明书中，当某个部分“包括”某个结构要素时，除非另有特别相反的记载，否则其意指还包括其他结构要素，而并不意味着排除其他结构要素。

在一实施方式中，本发明涉及发热伴血小板减少综合征病毒，其中，在L基因的ORF(6255bp)中表达的蛋白质的第1447位氨基酸为缬氨酸或第1913位氨基酸为赖氨酸，在M基因的ORF(3222bp)中表达的蛋白质的第83位氨基酸为酪氨酸、第404位氨基酸为苏氨酸或第904位氨基酸为缬氨酸。本发明的一实施例中，将上述病毒命名为B-1(CB3)。

在一实例中，上述发热伴血小板减少综合征病毒属于基因型B-1，可以为在分类为以往的基因型B的病毒的L基因的ORF(6255bp)中表达的蛋白质的作为第1447位氨基酸的异亮氨酸被缬氨酸取代、作为第1913位氨基酸的精氨酸被赖氨酸取代(序列13)、M基因的作为第904位氨基酸的异亮氨酸被缬氨酸取代的(序列14)病毒。

在一实例中，上述发热伴血小板减少综合征病毒可包括S基因，上述S基因包括包含序列1的碱基序列的L基因、包含序列2的碱基序列的M基因、包含序列3的碱基序列NP基因以及包含序列4的碱基序列的NS基因。

在一实例中，上述发热伴血小板减少综合征病毒可包含在L基因的ORF(6255bp)中表达的序列13的氨基酸序列、在M基因的ORF(3222bp)中表达的序列14的氨基酸序列、在NP基因的ORF中表达的序列15的氨基酸序列以及在NS基因的ORF中表达的序列16的氨基酸序列。

在一实施方式中，本发明涉及发热伴血小板减少综合征病毒，其中，在L基因的ORF(6255bp)中表达的蛋白质的第1447位氨基酸为异亮氨酸或第1913位氨基酸为精氨酸，在M基因的ORF(3222bp)中表达的蛋白质的第83位氨基酸为苯丙氨酸、第404位氨基酸为苏氨酸或第904位氨基酸为异亮氨酸。在本发明的一实施例中，将上述病毒命名为B-2(CB4)。

在一实例中，上述发热伴血小板减少综合征病毒属于基因型B-2，可以为分类为以往的基因型B的病毒的M基因的作为第83位氨基酸的酪氨酸被苯丙氨酸取代的病毒。

在一实例中，上述发热伴血小板减少综合征病毒可包括S基因，上述S基因包括包含序列5的碱基序列的L基因、包含序列6的碱基序列的M基因、包含序列7的碱基序列NP基因以及包含序列8的碱基序列的NS基因。

在一实例中，上述发热伴血小板减少综合征病毒可包含在L基因的ORF中表达的序列17的氨基酸序列、在M基因的ORF中表达的序列18的氨基酸序列、在NP基因的ORF中表达的序列19的氨基酸序列以及在NS基因的ORF中表达的序列20的氨基酸序列。

在一实施方式中，本发明涉及发热伴血小板减少综合征病毒，其中，在L基因的ORF(6255bp)中表达的蛋白质的第1447位氨基酸为异亮氨酸或第1913位氨基酸为精氨酸，在M基因的ORF(3222bp)中表达的蛋白质的第83位氨基酸为酪氨酸、第404位氨基酸为丙氨酸或第904位氨基酸为异亮氨酸。在本发明的一实施例中，将上述病毒命名为B-3(CB1)。

在一实例中，上述发热伴血小板减少综合征病毒属于基因型B-3，可以为分类为以往的基因型B的病毒的M基因的作为第404位氨基酸的苏氨酸被丙氨酸取代的病毒。

在一实例中，上述发热伴血小板减少综合征病毒可包括S基因，上述S基因包括包含序列9的碱基序列的L基因、包含序列10的碱基序列的M基因、包含序列11的碱基序列NP基因以及包含序列12的碱基序列的NS基因。

在一实例中，上述发热伴血小板减少综合征病毒可包含在L基因的ORF中表达的序列21的氨基酸序列、在M基因的ORF中表达的序列22的氨基酸序列、在NP基因的ORF中表达的序列23的氨基酸序列以及在NS基因的ORF中表达的序列24的氨基酸序列。

在本发明的一实施例中所分离的发热伴血小板减少综合征病毒的基因分析结果，它们的基因序列与公知的发热伴血小板减少综合征病毒的基因不同，通过对它们的系统学分类结果可知，每个基因为细化为至少三个的基因型，而并不是公知的一个B基因型组。

在本说明书中所使用的术语“取代”是指一个以上氨基酸或核苷酸分别被其他氨基酸或核苷酸代替。

本发明的发热伴血小板减少综合征病毒为负单链RNA病毒，其属于布尼亚病毒科(Bunyaviridae)、白蛉病毒属(phlebovirus)。并且，这种病毒为直径为80～100nm的球形病毒，以长角血蜱作为媒介，基因组由大(large(L))节段、中(medium(M))节段及小(small(S))节段组成，用于编码RNA依赖性RNA聚合酶(RNA dependent RNA polymerase，RdRp)、糖蛋白前体(glycoprotein precursor，M)，糖蛋白N(glycoprotein N，Gn)、糖蛋白C(glycoprotein C，Gc)、核衣壳蛋白(nucleocapsid protein，NP)及非结构蛋白(non-structural protein，NSs)等六个蛋白质。负链或反义链(针对用于编码病毒蛋白的正义链或正链的反义)以反义编码蛋白质或基因，为了表达至基因的蛋白质，生成正义链或正链RNA后，由此进行翻译来生成蛋白质。

在一实施方式中，本发明涉及包含发热伴血小板减少综合征病毒或其抗原作为有效成分的用于预防或治疗发热伴血小板减少综合征的免疫原性组合物。

在一实例中，本发明的免疫原性组合物可包含灭活的发热伴血小板减少综合征病毒和药剂学上可接受的载体(carrier)或佐剂(adjuvant)。

在一实例中，上述免疫原性组合物可以为疫苗组合物，其形态可选自由活疫苗、灭活疫苗、使用弱毒化发热伴血小板减少综合征病毒的基因生产的亚单位疫苗、载体疫苗、嵌合疫苗、DNA疫苗及RNA疫苗组成的组中。

在一实例中，上述免疫原性组合物可包含如下的发热伴血小板减少综合征病毒或它们的抗原作为有效成分：包括包含序列1的碱基序列的L基因、包含序列2的碱基序列的M基因以及包含序列3的碱基序列的S基因的发热伴血小板减少综合征病毒；包括包含序列4的碱基序列的L基因、包含序列5的碱基序列的M基因以及包含序列6的碱基序列的S基因的发热伴血小板减少综合征病毒；以及包括包含序列7的碱基序列的L基因、包含序列8的碱基序列的M基因以及包含序列9的碱基序列的S基因的发热伴血小板减少综合征病毒。

为了制备本发明的免疫原性组合物(即，疫苗)，本发明的病毒或其抗原可转化为生理学上可接受的形态。这可以基于对于流感的疫苗接种中所使用的疫苗的制备经验来实施(由Stickl，H.等公开。Dtsch.med.Wschr.99，2386-2392)。为了制备疫苗注射剂，例如，在安瓿瓶中，优选地，在玻璃安瓿瓶中在存在1％的人白蛋白及2％的蛋白胨的条件下的100ml的磷酸缓冲盐溶液(PBS)中进行冷冻干燥。不同地，疫苗注射剂在制剂化过程中通过对病毒依次进行冷冻-干燥来生成。这种制剂可含有如甘露醇、葡聚糖、糖类、甘氨酸、乳糖或聚乙烯吡咯烷酮等附加添加剂或者如抗氧化剂或非活性气体、稳定剂或适于向生物体内给药的重组蛋白(例如，人血清白蛋白)等其他辅助剂。接着，密封玻璃安瓿瓶并可在4℃至室温下储藏几个月。但是，除非另有其他要求，否则上述安瓿瓶可优选在小于-20℃的温度下储藏。

为了预防接种或治疗，冷冻干燥物溶解于0.1ml至0.5ml的水溶液中，优选地，溶解于生理盐水或tris缓冲液中，并能够以全身或局部，即，胃肠外、皮下、肌肉内或本领域的普通技术人员公知的任意其他给药途径给药。给药形态、服用量及给药次数可由本领域的普通技术人员通过公知的方式进行优化。但是，通常，患者接受第一次疫苗接种约一个月至六周后，接受第二次疫苗接种。

在本发明中，术语“预防”是指通过给药本发明的免疫原性组合物来抑制或延缓发热伴血小板减少综合征的发生、扩散及复发的所有行为。

在本说明书中所使用的术语“治疗”是指通过给药本发明的免疫原性组合物来使发热伴血小板减少综合征及由此引起的并发症的症状得到好转或改善的所有行为。只要是本发明所属技术领域的普通技术人员，通过参照韩国大韩韩医学会等中提供的材料来确认本发明的组合物为具有效果的疾病的正确标准，可判断改善、好转及治疗程度。

在本发明中结合有效成分来使用的术语“治疗有效量”是指针对由移植排斥反应引起的疾病的预防或治疗有效的量，本发明的组合物的治疗有效可根据如给药方法、目标部位、患者的状态等各种因素而不同。因此，对人体使用时，需要一起考虑安全性及效率性决定适当量的给药量。也可以从通过动物实验决定的有效量推断对人类使用的量。例如，在决定有效量时需要考虑的事项记载于Hardman and Limbird，eds.，Goodman and Gilman'sThe Pharmacological Basis of Therapeutics，10th ed.(2001)，Pergamon Press；以及E.W.Martin ed.，Remington's Pharmaceutical Sciences，18th ed.(1990)，MackPublishingCo.中。

以药学有效量给药本发明的药学组合物。在本发明中所使用的术语“药学有效量”是指以可适用于医学治疗的合理的利益/风险比充分治疗疾病且不引起副作用程度的量，有效剂量水平可根据包括患者的健康状态、饮食种类、重症度、药物的活性、对药物的敏感度、给药方法、给药时间、给药途径及排泄比例、疗程、配合或同时使用的药物在内的因素及其他医学领域中公知的因素来决定。本发明的组合物可作为单独的治疗剂给药或者可与其他治疗剂联用来给药，可与以往的治疗剂依次或者同时给药，可进行单次给药或多次给药。考虑到上述全部因素，优选地，给药在没有副作用的情况下可得到最大效果的量，这可由本领域的普通技术人员容易决定。

本发明的药学组合物可包含通常使用于生物学制剂中的载体、稀释剂、赋形剂或它们中两种以上的组合。在本发明中所使用的术语“药学上可接受”是指对于暴露在上述组合物中的细胞或人类没有毒性的特性。上述载体只要是将组合物适于传递至生物体内的载就不受特别限制，例如，可将在Merck Index，13th ed.，Merck&Co.Inc.中记载的化合物、生理盐水、无菌水、林格氏液、缓冲生理盐水、葡萄糖溶液、麦芽糊精溶液、丙三醇、乙醇及这些成分中的一种成分以上混合来利用，根据需要，可添加抗氧化剂、缓冲液、细胞抑制剂等其他常规的添加剂。并且，进一步添加稀释剂、分散剂、表面活性剂、结合剂及润滑剂来制剂化为如水溶液、悬浊液、乳浊液等注入用剂型、丸剂、胶囊、颗粒或片剂。进一步地，可利用本领域中适当的方法或在雷明顿药物科学(Remington's Pharmaceutical Science，MackPublishingCompany，Easton PA，18th，1990)中记载的方法并根据各种疾病或成分来进行优选的制剂化。

在一实例中，上述药学组合物可以为选自由口服剂型、外用剂、栓剂、灭菌注射用液及喷雾剂组成的组中的一种以上剂型，口服剂型或注射剂型更优选。

在本发明中所使用的术语“给药”是指以任意适当的方法向对象或患者提供规定的物质，可按照期望的方法进行胃肠外给药(例如，适用静脉内、皮下、腹腔内或局部注射剂型)或者口服给药，给药量的范围根据患者的体重、年龄、性别、健康状态、饮食、给药时间、给药方法、排泄率及疾病的重症度等而不同。用于本发明的组合物的口服给药的液态制剂为悬浊剂、内用液剂、乳剂、糖浆剂等，除了作为通常所使用的简单稀释剂的水、液体石蜡之外，还可包含如湿润剂、甜味剂、芳香剂、保存剂等多种赋形剂。用于胃肠外给药的制剂包括灭菌的水溶液、非水性溶剂、悬浊剂、乳剂、冷冻干燥制剂、栓剂等。还可以通过能够将活性物质移动至靶细胞的任意装置给药本发明的药学组合物。优选的给药方式及制剂为静脉注射剂、皮下注射剂、皮内注射剂、肌肉注射剂、点滴注射剂等。可通过生理盐溶液、林格氏液等水性溶剂、植物油、高级脂肪酸乙酯(例如，油酸乙酯等)、醇类(例如，乙醇、苯甲醇、丙二醇、丙三醇等)等非水性溶剂等来制备注射剂，可包含用于防止变质的稳定剂(例如，抗坏血酸、亚硫酸氢钠、焦亚硫酸钠、BHA、生育酚、EDTA等)、乳化剂、用于调节pH的缓冲剂、用于抑制微生物繁殖的保存剂(例如，硝酸苯汞、硫柳汞、苯扎氯铵、苯酚、甲酚、苄醇等)等药学载体。

在本发明中所使用的术语“对象”是指上述癌症发病或者会发病的包括人类在内的猴、牛、马、羊、猪、鸡、火鸡、鹌鹑、猫、狗、小鼠、大鼠、兔或豚鼠等所有动物，“样品”可以为从这些动物中分离的全血、血浆、血清、尿或唾液。

本发明的药学组合物还可以包含药剂学上可接受的添加剂，此时，作为药剂学上可接受的添加剂可使用淀粉、糊化淀粉、微晶纤维素、乳糖、聚维酮、胶态二氧化硅、磷酸氢钙、乳糖、甘露醇、饴糖、阿拉伯树胶、预胶化淀粉、玉米淀粉、粉状纤维素、羟丙基纤维素、欧巴代、羧甲淀粉钠、巴西棕榈蜡、合成硅酸铝、硬脂酸、硬脂酸镁、硬脂酸铝、硬脂酸钙、白糖、葡萄糖、山梨糖醇及滑石粉等。优选地，相对于上述组合物，可包含0.1重量份至90重量份的本发明药剂学上可接受的添加剂，但并不限定于此。

在一实施方式中，本发明涉及使用本发明的病毒或其抗原进行免疫应答来生产的抗体。

上述抗体不仅是全(whole)抗体形态，而且还包含抗体分子的功能性片段。全抗体为具有两个全长的轻链(light chain)及两个全长的重链(heavy chain)的结构，各个轻链通过二硫键(disulfide bond)与重链连接。抗体分子的功能性片段是指具有抗原结合功能的片段，抗体片段例如包括：(i)由轻链的可变区(VL)及重链的可变区(VH)和轻链的恒定区(CL)及重链的第一个恒定区(CH1)组成的Fab片段；(ii)由VH结构域及CH1结构域组成的Fd片段；(iii)由单抗体的VL结构域及VH结构域组成的Fv片段；(iv)由VH结构域组成的dAb片段(Ward ES et al.，Nature 341:544-546(1989)]；(v)分离的CDR区；(vi)包含两个连接的Fab片段的作为二价片段的F(ab')2片段；(vii)通过以使VH结构域及VL结构域形成抗原结合部位的方式结合的肽衔接物结合的单链Fv分子(scFv)；(viii)双特异性单链Fv二聚物(PCT/US92/09965)；以及(ix)通过基因融合制备的作为多价或多特异性片段的双体(diabody)WO94/13804)等。

在一实施方式中，本发明涉及包含发热伴血小板减少综合征病毒或其抗原或针对其的抗体的发热伴血小板减少综合征病毒的诊断试剂盒。

在一实例中，上述试剂盒可包括包含本发明的病毒的病毒试样及上述抗原-抗体复合物检测用试剂。上述抗原-抗体复合物检测用试剂包括放射免疫分析、酶联免疫吸附测定(Enzyme linked immunosorbent assay，ELISA)或免疫荧光分析用试剂。

在一实例中，可利用可简单地通过抗原抗体结合检测到的奥克特洛尼(Ouchterlony)平板、免疫印迹、如Crossed IE、Rocket IE、Fused Rocket IE、Affinity IE等免疫电泳(Immuno Electrophoresis)来实现抗原-抗体复合物的检测。在这种方法中所使用的试剂或物质为公知的，例如，可通过抗原-抗体之间反应、和与抗原特异性结合的底物、核酸或肽适体、与复合物相互作用的受体或配体或辅因子之前的反应来检测，或者可利用质量分析器。可将上述与本发明的抗原-抗体复合物特异性相互作用或结合的试剂或物质与核方式或纳米粒子(nanoparticle)一起使用。上述免疫分析或免疫染色的方法记载于Enzyme Immunoassay，E.T.Maggio，ed.，CRC Press，Boca Raton，Florida，1980；Gaastra，W.,Enzyme-linked immunosorbent assay(ELISA)，in Methods in Molecular Biology，Vol.1，Walker，J.M.ed.,Humana Press，NJ，1984中。可通过分析上述的免疫分析过程的最终信号的强度，即，进行与正常试样之间的信号对照来诊断是否感染。

在一实施方式中，本发明涉及包含发热伴血小板减少综合征病毒或其抗原或针对其的抗体的诊断组合物。

优选地，以能够被检测的方式标记诊断组合物中所使用的本发明的上述化合物。在标记生物分子时可使用的多种方法为本领域的普通技术人员公知的，在本发明的范畴内考虑。上述多种方法记载于Tijssen，'Practice and theory of enzyme immuno assays'，Burden,RHand von Knippenburg(Eds)，Volume 15(1985)，'Basic methods in molecularbiology'；Davis LG，Dibmer MD；Battey Elsevier(1990)，Mayer et al.，(Eds)'Immunochemical methods in cell and molecular biology'Academic Press，London(1987)，or in the series'Methods in Enzymology'，Academic Press，Inc中。

本领域的普通技术人员公知的有标记方法和多种其他标记。可在本发明中使用的标记种类例如有酶、放射性同位素、胶体态金属、荧光化合物、化学发光化合物及生物发光化合物。

通常所使用的标记为荧光物质包括(例如，荧光黄、罗丹明、德克萨斯红等)、酶(例如，辣根过氧化物酶、β-半乳糖苷酶、碱性磷酸酶)、放射性同位素(例如，

检测方法为射线自显迹法、荧光显微镜、直接及间接酶反应等，但并不限定于此。通常所使用的检测分析法为放射性同位素或非放射性同位素方法。其中，通常使用免疫印迹、叠加分析法、放射免疫分析(Radioimmuno Assay，RIA)及免疫放射分析(ImmuneRadioimmunometric Assay，IRMA)、酶联免疫分析(Enzyme Immuno Assay，FIA)、酶联免疫吸附分析(Enzyme Linked Immuno Sorbent Assay，ELISA)、荧光免疫分析(FluorescentImmuno Assay，FIA)以及化学发光免疫分析(Chemioluminescent Immune Assay，CLIA)。

在一实施方式中，本发明涉及发热伴血小板减少综合征病毒抗体的检测方法，包括：在可形成抗原-抗体复合物的条件下，使从样品中分离的试样与本发明的病毒或其抗原接触的步骤；以及检测抗原-抗体复合物的形成的步骤。

在一实施方式中，本发明涉及在非人类动物中生产针对发热伴血小板减少综合征病毒的抗血清的方法，包括：向非人类动物给药适于诱导免疫应答的有效量的本发明的病毒或其抗原的步骤；以及收集含有针对上述发热伴血小板减少综合征病毒的抗体的抗血清或血浆的步骤。

在一实施方式中，本发明涉及与发热伴血小板减少综合征的诊断有关的信息的提供方法，包括：通过使从样品中分离的试样与本发明的病毒或其抗原接触来形成抗原-抗体复合物的步骤；以及检测上述抗原-抗体复合物的形成的步骤。

具体实施方式

通过以下实施例更详细地说明本发明。但是，以下实施例仅用于使本发明的内容具体化，而本发明并不限定于此。

实施例1.分离病毒

利用大学附属医院就诊患者中疑似发热伴血小板减少综合征的患者的血液、动物(山羊及遗弃犬)的血液及野生蜱均质物并通过实时荧光定量PCR(real time PCR)、PCR及ELISA分析确认发热伴血小板减少综合征病毒的阳性/阴性。具体地，感染病毒前天，将VeroE6细胞分株于12孔板中后，以大于60％的细胞密度进行培养后，用PBS清洗细胞，将300μL的疑似感染患者的血清(以3000rpm离心分离整个血液20分钟来获得的血清)处理1小时来感染。感染后，去除血清并用PBS清洗后，用含1％的FBS的DMEM培养基更换并培养2周。2周后，通过RT-PCR(逆转录(reverse transcription)后用实时荧光定量PCR确认)及免疫荧光分析法(immuno fluoresence assay)(在实验室，将小鼠(mouse)发热伴血小板减少综合征病毒NP抗体用作第一抗体以及将共轭FITC的抗体用作第二抗体)确认病毒分离与否，在没有分离病毒的情况下，通过将第一次感染过的上清液感染在另一个VeroE6细胞的方式分离病毒。将分离的病毒命名为CB3/2016、CB7/2017及CB6/2016。

实施例2.分析分离的病毒的基因

分别对利用Vero E6细胞分离的病毒CB3/2016、CB7/2017及CB6/2016进行逆转录(Reverse-transcription)、PCR及下一代测序(Next generation sequencing，NGS)来确认各病毒的L、M、S(NP、NS)基因的全长序列。具体地，从各病毒中提取RNA并通过逆转录(Reverse-transcription)PCR来制备cDNA。之后，对各SFTS病毒的L、M、S基因进行PCR来获得各自的全长基因。使用NGS方法进行基因序列分析，使用illumina nextera XT kit并根据由因美纳(illumina)公司提供的协议对各病毒的L、M、S基因进行标签化(tagmentation)及索引PCR(index PCR)。之后，将最终样品利用illimina miniseq测序系统生成Fasta Q文件，利用CLC main workbench program所生成的文件的基因序列分析各自的全长基因序列。将确认到的基因序列与在韩国、中国及日本中分离的以往的病毒的基因整合来进行基因分析，通过其结果确认，在本发明中分离的发热伴血小板减少综合征病毒CB1、CB3及CB4为与目前在中国或韩国分离的病毒(YuXJ et al.,N.Engl.J.Med.2011)及在韩国首次分离的(Gangwon/2012)病毒的基因具有遗传性区别的新型基因型(genotype)的发热伴血小板减少综合征病毒。同时，使用MEGA7.0程序对本发明的病毒与在韩国、中国、日本分离的病毒的L、M、S(NP、NS)基因进行系统学基因分析，通过其结果确认，本发明的病毒接近于韩国分离株所属最多的B组，但是，基因L、M及S(NP及NS)基因中显示与以往的病毒不同之处，细化为至少三个以上组来区分(图1至图4)。对此，将在本发明分离的三种基因型的发热伴血小板减少综合征病毒细化为B-1(CB3/2016)、B-2(CB7/2017)及B-3(CB6/2016)来进行命名。

实施例3.确认各病毒的L、M及S基因氨基酸序列差异

以在本发明分离的新型细化基因型B-1、B-2及B-3的病毒的L、M及S基因的可读框(open reading frame，ORF)为基准分析氨基酸序列，其结果，L及M基因具有差异。具体地，B基因型中L基因的ORF(6255bp)编码RdRp，本发明的基因型B-1病毒中，RdRp的第1447位氨基酸为缬氨酸或第1913位氨基酸为赖氨酸，基因型B-2病毒及B-3病毒中，RdRp的第1447位氨基酸为异亮氨酸或第1913位氨基酸为精氨酸(图5的A部分及表1)。

表1

分析在本发明分离的新型细化基因型B-1、B-2及B-3的病毒的L、M及S基因的氨基酸序列，其结果，L及M基因具有差异。具体地，B基因型中M基因的ORF(3222bp)编码Gn及Gc蛋白，本发明的基因型B-1病毒中，M基因的ORF的第83位氨基酸为酪氨酸、第404位氨基酸为苏氨酸或第904位氨基酸为缬氨酸，基因型B-2病毒中，M基因的ORF的第83位氨基酸为苯丙氨酸、第404位氨基酸为苏氨酸或第904位氨基酸为异亮氨酸，基因型B-3病毒中，M基因的ORF的第83位氨基酸为酪氨酸、第404位氨基酸为丙氨酸或第904位氨基酸为异亮氨酸(图5的B部分及表1)。

实施例4.比较各基因型的基因的同源性

针对包括本发明的细化基因型B-1、B-2及B-3在内的目前在韩国分离的发热伴血小板减少综合征病毒进行基因分析，比较分析了各基因型的L、M及S基因同源性。通过其结果确认，在属于相同基因型的病毒之间的基因同源性(nucleotide level)为约96～100％，与此相反，不同基因型病毒之间的基因同源性较低，为91～97％(表2至表5)。并且，在本发明的基因型B-3组的情况下，相同组中的同源性较低，为约95～100％左右，在B-3组中也可以细化为其他基因型组。

表2

比较L基因的同源性

表3

比较M基因的同源性

表4

比较S(NP)基因的同源性

表5

比较S(NS)基因的同源性

实施例5.分析各基因型的交叉免疫原性及确认疫苗效果

通过FRNT50(fifty percent of Focus reduction neutralization test)分析各基因型的交叉免疫原性。具体地，使在本发明分离的新型细化基因型B-1、B-2及B-3的病毒大量增殖后，分别添加福尔马林(0.05％)进行灭活后，通过三次的病毒分离(isolation)确认灭活与否。采用20％的蔗糖(sucrose)灭活的上述疫苗(inactivated whole vaccine)进行超离心分离来生产蛋白质后，将其对雪貂进行免疫化。2周后，进一步对雪貂进行免疫化后(两次免疫间隔之间为两周)，采血并分离血清。在56℃的温度下灭活所分离的血清30分钟后，以1/10比例稀释后，进行每次2倍的阶段性稀释。在37℃的温度下，将以200FFU/ml稀释的病毒与阶段性稀释的病毒以1：1的比例进行反应。清洗分株于6孔板中的VeroE6细胞后，用经上述反应的病毒进行感染，1小时后进行清洗后，将含1％的FBS的0.8％的DMEM琼脂糖凝胶倒入细胞中。感染5天后，采用福尔马林固定3小时后，清洗三次后，在室温下各进行5分钟的10％的triton x-100处理。之后，清洗三次并用5％的BSA进行封闭。使用所生产的多克隆NP抗体(polyclonal NP antibody)作为第一抗体来进行培养后清洗三次，用第二抗体使HRP共轭(HRP conjugated)抗体反应1小时并清洗后，用DAB发色来确认结果。应解释为，比仅感染病毒的孔的病灶形成(foucus forming)降低至50％的值为有效。

表6

确认B-1、B-2及B-3的交叉免疫原性的结果如上述表6所示，针对各病毒显示出最高的血清抵抗。因此，在属于相同的基因型的病毒之间显示出高交叉中和反应性，但在各自不同的基因型之间的病毒之间显示出较低的中和反应性。

使在本发明分离的新型细化基因型B-1、B-2及B-3的病毒大量增殖后，分别添加福尔马林(0.05％)进行灭活后，通过三次的病毒分离(isolation)确认灭活与否。对各病毒将灭活的上述疫苗(inactivated whole vaccine)以两周为间隔对每五只雪貂进行免疫化两次后，以1×10

通过挑战接种结果确认，对照组动物在10天内都在被挑战病毒感染时死亡，但接种疫苗的组的所有雪貂存活，并在感染2～8天后确认体温上升、体重下降，之后开始恢复(图6)。

概括以上的结果，在发热伴血小板减少综合征病毒中存在具有多种基因的多种基因型的病毒，在属于相同基因型的病毒之间显示出较高基因同源性及低交叉免疫原性，与其他基因型的病毒之间显示出较低基因同源性及低交叉免疫原性，因此，为了产生针对多种基因型的交叉免疫原性，可推断为某个特定基因型的病毒的防御能力是受限的。

因此，可将属于本发明的细化基因型B-1、B-2及B-3的新型病毒CB3/2016、CB7/2017及CB6/2016有用地利用为对基因型B的发热伴血小板减少综合征病毒具有优秀的交叉免疫原性的疫苗。

<110> 鉴定生物株式会社

<120> 新型发热伴血小板减少综合征病毒

<130> PO1903-006

<160> 24

<170> KoPatentIn 3.0

<210> 1

<211> 6255

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 L基因

<400> 1

atggacttgg aagtgctttg tggtaggata aacgtggaga atgggctgtc tcttggagaa 60

ccaggcctgt acgaccaaat ctacgacagg ccagggctgc cagacctaga tgtgactgtc 120

gatgccacag gtgtgacagt ggacataggg gctgtgccag actcagcatc acaactgggc 180

tcatcaatca atgctgggtt gatcacaatc cagctctctg aagcatataa gatcaatcat 240

gacttcacat tttctggcct gtcaaagaca acagaccgac gcctctcaga ggtattcccc 300

attacccatg atggttctga tgggatgacc cctgatgtga tccacaccag attggatgga 360

actattgtgg tggttgaatt ttcaaccact aggagccata acattggggg cctggaggca 420

gcatatagga caaagataga aaaatatagg gacccaatct caaggcgtgt tgatatcatg 480

gagaacccga gagtcttctt tggtgttatt gtagtctcgt caggaggggt tctgtccaac 540

atgcccctga ctcaggatga ggcagaggag ctcatgtaca ggttctgcat agccaatgaa 600

atctacacta aggctagatc tatggatgca gacattgagc tacagaagag tgaagaagag 660

cttgaggcta tcagcagggc actttcattc ttcagtttgt tcgagcctaa cattgaaaga 720

gtggaaggaa cattccccaa ttcagaaatt gagatgctgg aacagtttct ctcaacacca 780

gctgatgttg acttcatcac caagaccctc aaagcaaaag aggtggaggc ctatgctgat 840

ctttgtgaca gccactacct aaagcctgaa aaaaccattc aggagcgtct agagatcaat 900

agatgtgagg ctattgacaa aactcaggac ctcctagctg gcctacatgc aaggagcaac 960

aagcaaacat cattgaatcg agggacagtc aaactcccgc cctggctgcc aaagccatca 1020

agtgagtcaa tagacatcaa gaccgactca ggctttggtt ccttaatgga tcatggcgca 1080

tatggtgagc tatgggcaaa gtgccttcta gatgtctcgt taggcaatgt ggagggggta 1140

gtcagtgacc ctgcaaaaga gcttgacatt gctatctctg atgacccaga aaaagacacc 1200

cccaaagagg caaagataac ctataggcga ttcaagcctg ccttaagttc aagtgcccgg 1260

caagaatttt ctctccaagg agtggagggg aagaagtgga agagaatggc agcaaaccag 1320

aagaaagaga aggagtccca tgagacattg agccctttct tggatgttga agacattggg 1380

gatttcctga cattcaacaa tcttcttgca gattcgaggt atggagatga gtccatccag 1440

agagctgtgt caatcttgtt ggaaaaggca tctgccatgc aggacacaga gctcactcat 1500

gctctcaacg actcattcaa gaggaaccta agcagcaatg tggttcagtg gtccctttgg 1560

gtttcctgtt tggcgcagga gctagctagt gctctgaagc agcactgcag ggctggtgag 1620

ttcatcatca agaagctgaa gttctggcct atctatgtca ttatcaagcc gaccaaatcg 1680

tcatctcaca tcttctacag cttagggatc cgcaaggctg acgtgacaag gaggctcact 1740

ggtagagtct tctctgacac cattgatgca ggggaatggg agctaacaga gttcaaaagc 1800

ctgaagacat gtaagctcac gaaccttgtc aacttaccat gcaccatgct gaactcaata 1860

gctttctgga gagagaagct gggcgtggct ccatggctgg tccggaagcc ttgttcagag 1920

ctcagggagc aggtgggcct gaccttcctg atcagtctgg aggacaagtc taagactgag 1980

gagatcatca ccttgacaag gtacacccag atggagggct ttgtctctcc tcccatgctg 2040

cccaaacccc aaaagatgct agggaaactg gatggacctt tgagaaccaa gctacaggtt 2100

tacctcctca ggaagcatct ggattgcatg gtgcgaattg cttctcagcc attcagccta 2160

atcccaagag aggggagagt agaatgggga ggaacattcc atgccatctc aggccggtcc 2220

acaaatcttg agaatatggt gaacagctgg tacattgggt actacaagaa caaagaggag 2280

tcaacagaac taaatgctct cggagaaatg tataagaaga ttgtggagat ggaagaggac 2340

aagcccagca gccctgagtt tctggggtgg ggggacactg attcccctaa gaagcatgaa 2400

ttctcacgga gcttcctgag agctgcttgc tcatctctgg aaagagaaat tgctcagcga 2460

catggaagac aatggaagca gaaccttgag gagcgagtcc tgagagagat tgggaccaag 2520

aacatcctgg accttgcatc catgaaggct actagcaact tttccaaaga ctgggagctc 2580

tactcagaag tccagaccaa agagtaccat aggtccaaac tgctggagaa gatggccaca 2640

ttgattgaga agggggttat gtggtacatt gatgctgtgg gtcaggcatg gaaggcagtt 2700

ctggatgacg ggtgcatgcg aatctgtctc ttcaaaaaga atcagcatgg tggcctcaga 2760

gagatctacg ttatggatgc aaatgcccgg ctcgtgcagt ttggggttga gaccatggct 2820

aggtgtgtct gtgagctgag cccacatgag actgttgcca accctaggct caagaattcc 2880

atcatagaga accatgggct gaagtcagcc cgtagtcttg gccctggctc tataaacata 2940

aactcatcca atgatgccag gaagtggaat caggggcact acacaacaaa gctagctcta 3000

gttctttgtt ggttcatgcc agccaaattc cacagattca tttgggctgc catttccatg 3060

tttcggagaa aaaagatgat ggtggaccta aggtttttag ctcacctcag ttctaaatct 3120

gagtctaggt catctgatcc atttagggaa gcaatgacag acgccttcca tggcaatagg 3180

gaagtctcat ggatggacaa agggcgaact tacataaaga cagagacagg tatgatgcag 3240

ggtatactgc actttacatc cagcctcctc cactcttgtg ttcagagctt ttacaagtct 3300

tatttcgtct cgaaactcaa ggagggctac atgggagaaa gcatcaatgg ggtggtggat 3360

gtcatagaag gctctgacga ctcagcgatc atgatcagca tacgccccaa gtcagacatg 3420

gatgaagtcc gatcaaggtt ctttgttgct aacttactcc actctgtaaa gttcttgaac 3480

cctttgtttg ggatctactc atcagagaaa tcaacagtga acacagtgta ttgtgtcgag 3540

tataactctg aattccattt ccacaggcac ttggttcgac ccacactgag atggatagca 3600

gcatctcacc aaatctcaga gactgaggcc cttgcaagca ggcaagagga ttattcaaac 3660

cttctaaccc agtgcttgga gggaggggcc tcattctctc ttacctacct catacagtgc 3720

gctcagctcc tgcaccacta catgcttcta ggactatgct tacacccctt gtttggaact 3780

ttcatgggga tgctgatatc agacccagat ccagccctag ggttcttcct catggacaac 3840

cctgcattcg caggaggagc aggatttaga ttcaatctgt ggagagcctg caagactaca 3900

gaccttgggc ggaagtatgc atattatttt aatgagatac agggtaaaac aaagggagat 3960

gaggactaca gagctctgga cgccacatca ggaggaaccc tcagccactc tgttatggtg 4020

tactgggggg acaggaagaa gtatcaggcc ttattgaaca ggatgggcct tcctgaggac 4080

tgggtggagc agatagatga gaatcccggt gtcctttaca ggagagctgc caacaagaag 4140

gaactactct taaaactggc agagaaggtt cattcacctg gtgtgactag cagcctgagt 4200

aaagggcatg tagtgcctcg ggtggtggca gcaggagtat accttctctc acgccattgc 4260

tttcgcttta gctcaagcat ccatggaagg ggctcagcac agaaggctag ccttataaaa 4320

ctgttgatga tgtcttctgt ttctgccatg aagcatgggg gctcactaaa ccctaatcag 4380

gagcgaatgc tcttccctca ggctcaagag tatgacagag tatgcacatt gcttgaggag 4440

gttgaacacc taacagggaa atttgttgtt agggagagga acattgtcag gagccgcata 4500

gacttgttcc aagagccagt ggacttgcgg tgcaaggcag aagatctggt gtcagaggtg 4560

tggtttggcc tgaaaaggac taaacttgga ccccgtctcc tcaaggaaga gtgggacaaa 4620

cttagggcct catttgcatg gctgagcaca gacccatctg aaacattgag ggatggtcct 4680

tttcttagcc atgtgcagtt taggaacttc atagcccacg ttgatgccaa atcaagatca 4740

gtcaggctcc taggtgcccc cgtaaagaag tcaggtgggg tcaccactat aagccaagta 4800

gtcagaatga acttcttccc aggttttagc ctagaagctg agaagagctt agacaatcag 4860

gaaagacttg agagcatctc catcctcaag catgtcttgt tcatggtctt gaatggccca 4920

tacactgagg agtacaagct ggaaatgatc atagaggcct tctctactct tgtgatacct 4980

cagccatcag aggtcatcag gaaatcaagg accatgactt tgtgcctctt atcaaattac 5040

ttgtctagta ggggtgggtc cattctagac cagattgaga gggcacagtc aggcactcta 5100

gggggcttca gcaagcccca gaagactttc attaggccag gaggtggtat cggctacaag 5160

ggaaagggtg tgtggactgg agtgatggag gacacccatg ttcaaattct gatagatgga 5220

gatgggacta gtaactggct tgaggagatc aggctcagta gtgatgccag actttatgat 5280

gtcattgagt ccatccgaag gttatgtgat gacctcggga tcaacaacag ggtggcatct 5340

gcatatagag gccattgcat ggttaggctg agtggattca agatcaagcc agcatcaagg 5400

actgatggct gcccagtcag gattatggaa aggggcttca ggatcaggga actccaaaac 5460

ccagatgagg tcaagatgag agtgagaggt gacatcctca acctctctgt caccattcaa 5520

gaaggaaggg tcatgaacat tctaagctac aggccgagag acactgatat atcagaatca 5580

gccgcagcat atctctggag caatcgagac ctcttctcct ttgggaagaa ggagccatcc 5640

tgcagctgga tctgcttgaa aactcttgac aattgggcct ggtcacatgc ctcagttctc 5700

ctggcaaatg ataggaagac ccaaggcatt gataataagg ctatggggaa cattttcagg 5760

gactgtctcg agggttctct tagaaagcaa gggctgatga ggtcaaagct cacagagatg 5820

gtggagaaga atgtagttcc tttaacaact caagagcttg tcgacatcct ggaggaggac 5880

atagactttt cagatgtcat agctgtggaa ctctcagagg gatcacttga tattgaatcc 5940

atctttgatg gggcacctat cttgtggtct gctgaggtgg aagagtttgg ggaaggagtg 6000

gtggctgtga gctattccag taagtactat catctaaccc tgatggacca agctgccatc 6060

acaatgtgtg cgatcatggg taaggaaggc tgtagagggc tccttactga gaagagatgc 6120

atggcagcca tacgagagca ggtacggcca ttcctcatat tcctgcaaat ccctgaggat 6180

agcatttctt gggtgtctga tcagttctgc gactccaggg gtcttgatga ggagagcacc 6240

attatgtggg gttga 6255

<210> 2

<211> 3222

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 M基因

<400> 2

atgatgaaag tcatctggtt ctcctctctg atctgcttag tcattcaatg cagtggggat 60

acgggtccaa tcatatgcgc agggcccatc cactcaaaca agagtgccaa cataccccac 120

ctgcttggct actctgagaa gatttgtcag atagatcggc tgatacatgt ttcgtcatgg 180

ctgagaaacc attcacaatt tcagggctat gtggggcagc gaggtggacg ctctcaggta 240

agctattacc cagctgaaaa ctcttactca aggtggagtg gacttctaag cccctgtgat 300

gcagattggc ttgggatgct tgttgtgaag aaggccaaag ggtctgatat gatagttcct 360

gggccttcat acaagggaaa agtctttttt gaacggccaa cttttgatgg atacgtaggc 420

tggggctgtg gcagtgggaa gtcaaggaca gagtcagggg agctctgcag ctcagactca 480

gggaccagtt ccggtcttct gccctcagat agggttctct ggataggtga tgttgcttgc 540

cagcctatga cacccatccc tgaggagaca tttctggagc tgaagagttt tagccagagt 600

gaattcccag acatatgcaa aattgatggc attgtgttca accagtgtga gagtgagagt 660

ctacctcaac ccttagatgt tgcgtggatg gatgtaggcc actctcataa aatcatcatg 720

agggagcaca agactaaatg ggtacaagag agctcatcta aggattttgt gtgctacaag 780

gaagggactg ggccatgttc tgaatcagaa gaaaagactt gcaagaccag tggatcatgt 840

aggggggaca tgcagttttg caaggtggca ggttgtgaac atggggaaga agcatctgat 900

gccaagtgta gatgctcact agtgcacaag cccggggaag ttgttgtgtc atatggaggg 960

atgcgtgtca gaccaaagtg ttatggcttc tccagaatga tggcaacact agaggtgaac 1020

ccaccagagc aaaggattgg ccaatgcact ggctgccatc ttgaatgcat aaatgggggt 1080

gtgaggctaa tcactctgac tagtgagctc aagtcagcta ctgtctgtgc ttcccacttt 1140

tgtagttctg ccacaagtgg caagaaaagc acggagattc aatttcactc agggtcatta 1200

gttgggaaaa caacaataca cgtcaaaggg gctttggtgg atggaactga attcacattt 1260

gagggcagtt gcatgttccc agatggttgt gacgcagtgg actgcacatt ctgtcgtgag 1320

tttctaaaaa atcctcagtg ctaccctgca aagaaatggc tgttcatcat tattgtcatc 1380

ctccttggat atgcaggcct catgctactt accaatgtcc ttaaggcaat cggggtttgg 1440

ggatcatggg tcatagctcc agtgaagcta atgtttgcca tcataaagaa actgatgaga 1500

tctgtgagct gcttgatggg gaaattaatg gataggggaa ggcaagtgat ccatgaagaa 1560

ataggggaga atagagaggg caaccaagat gatgttagga tcgagatggc aagacccaga 1620

agggtaaggc attggatgta ctcacctgtc atcctgacta ttctagcaat tgggcttgcc 1680

gagggctgcg atgagatggt ccatgctgac tccaaacttg tttcgtgcaa gcaagggagc 1740

ggaaacatga aggaatgtgt cacaactggg agggcactcc ttcctgcggt gaacccagga 1800

caagaggcat gtctgcactt cacggcacct gggagtccgg actcaaaatg tctcaaaatt 1860

aaggtcaaga ggattaacct aaaatgtaag aagtcatcat catattttgt tcctgatgct 1920

cggtctaggt gtacatctgt gaggagatgt cgctgggcag gagactgcca gtctgggtgc 1980

ccctctcatt tcacgtccaa ctccttctct gatgattggg caggtaaaat ggacagggca 2040

ggtctaggat tcagtgggtg ctctgatgga tgtggaggag cagcctgcgg ctgctttaat 2100

gcagcccctt catgcatctt ttggaggaaa tgggtagaga acccgcatgg gatcatctgg 2160

aaagtatctc catgtgctgc atgggtccca tcagcagtca tagagctaac aatgccctca 2220

ggggaagtga ggacattcca ccccatgagc ggcatcccta cacaagtctt caagggtgtg 2280

agtgtgacgt acttaggctc agatatggag gtgtctggct tgactgacct gtgtgagata 2340

gaagagctca agtccaagaa gctggcatta gccccctgca atcaggctgg catgggggtt 2400

gtaggcaagg ttggagagat acagtgcagt agcgaggaaa gtgcccgtac cataaaaaaa 2460

gatgggtgta tatggaatgc tgaccttgtg ggcatagagc tacgagtgga tgacgctgtg 2520

tgctactcta agatcactag tgtggaggca gttgcaaact actctgccat acccaccact 2580

attggggggc tgaggtttga gagaagccat gacagccagg gtaaaatatc tggtagcccc 2640

ttagatataa cagccataag agggtctttt tcagttaatt atagaggcct tcgactgagc 2700

ctctcagagg ttactgctac ttgcacagga gaggtgacga atgtgagtgg gtgttactct 2760

tgcatgacag gcgccaaagt ctccatcaaa ctgcatagca gcaaaaatag cactgcccat 2820

gtaagatgca aaggggatga gacagcattc agtgtcctag tgggagttca tagctatact 2880

gtcagtctca gctttgacca tgcagtggtc gatgagcagt gccagctgaa ctgtggaggg 2940

catgagagtc aagtgactct aaaaggcaac ctcatcttcc tggatgtccc aaaatttgtg 3000

gatggcagct atatgcagac atatcatagt tctgtgccca caggggccaa catcccaagc 3060

cctacagact ggctgaatgc cttgttcggc aatgggctga gtaggtggat tctgggggta 3120

ataggggttc tactgggggg attggctctc tttttcttaa tcatgtctct gttcaaattg 3180

ggaacaaaac aggtatttcg atcaaggacg aagctggctt aa 3222

<210> 3

<211> 738

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 NP基因

<400> 3

atgtcagagt ggtccaggat tgcagtggag tttggtgagc agcagctcaa tttgacggag 60

cttgaggact tcgcgagaga gctggcctat gaaggccttg atcctgcttt gatcatcaag 120

aagctgaagg agacaggtgg ggatgattgg gtgagggata caaagttcat cattgtcttt 180

gccctgactc gaggcaataa gattgtcaag gcatcaggga aaatgtcaaa ctcagggtct 240

aagaggttga tggcactcca agagaagtat ggactggttg agagggcaga aaccaggctc 300

tcaatcactc ctgtgagggt ggcacagagc ctacccactt ggacatgtgc tgctgcagca 360

gccttaaagg agtatcttcc agttgggcca gctgtcatga acctgaaggt cgagaattat 420

cctccagaga tgatgtgcat ggcctttggg tccctgattc caactgcggg ggtgtcagaa 480

gctacaacga agaccctgat ggaggcctac tctctgtggc aagatgcctt cacaaagact 540

atcaatgtga agatgcgcgg agccagtaag acagaggttt acaactcctt cagggatcct 600

ctccatgctg ctgtgaactt cgtctttttc ccccaagatg ttcgggtgaa gtggctgaag 660

gccaagggaa tccttggccc agatggggtc cccagcagag ctgctgaggt tgctgctgct 720

gcttacagaa acctgtaa 738

<210> 4

<211> 882

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 NS基因

<400> 4

atgtcgctga gcaaatgctc caacgttgac ctcaaatctg tggcaatgaa tgccaacact 60

gtcaggcttg agccatctct aggagagtac cccactctta ggagagacct cgttgaatgc 120

tcttgtagtg tgttgactct atcaatggtt aagaggatgg gcaagatgac caacacagta 180

tggttgtttg gtaacccaaa aaatcctctt caccagcttg agcctggact cgagcagctg 240

ttggacatgt actacaagga catgaggtgc tactcccaga gagagctgag tgctcttagg 300

tggcctagtg ggaagccatc tgtatggttc ctgcaggcag ctcatatgtt cttctccatc 360

aagaacagct gggcaatgga aaccggcaga gagaattggc ggggcctctt ccacaggata 420

acaaaaggca aaaagtatct ttttgaagga gacatgatat tggattctct tgaggccata 480

gagaagcgaa ggcttagact tgggctacct gagatcctaa taactggact atccccgatt 540

ctggatgtgg ccctcctcca gatagagtca cttgcaaggc taagaggcat gagcttgaac 600

caccacttat tcacatcttc ctcattgcgt aagcctttgt tggactgttg ggacttcttt 660

attcctatcc ggaaaaagag gacagatggc tcatacagta tcttggatga ggatgatgaa 720

cttggggtcc ttcaaggtta cccatatctg atggcacact atttgaatag gtgcccattc 780

cacaacctca tcaggtttga tgaagagctg agaactgcag ccctaaacac catctgggga 840

agagattggc cggccattgg tgacctcccg aaggaggtct aa 882

<210> 5

<211> 6255

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 L基因

<400> 5

atgaacttgg aagtgctttg tggtaggata aacgtggaga atgggctgtc tcttggagaa 60

ccaggcctgt acgaccaaat ctacgacagg ccagggctgc cagacctaga tgtgactgtc 120

gatgccacag gtgtgacagt ggacataggg gctgtaccag actcagcatc acaactgggc 180

tcatcaatca atgctgggtt gatcacaatc cagctctctg aagcatataa gatcaatcat 240

gacttcacat tttctggcct gtcaaagaca acagaccgac gcctctcaga ggtattcccc 300

attacccatg atggttcaga tgggatgacc cctgatgtga ttcataccag attggatgga 360

accattgtgg tggttgaatt ttcaaccact aggagccata acattggggg cctggagacg 420

gcatatagaa caaagataga gaaatatagg gacccaatct caaggcgtgt tgatatcatg 480

gagaacccga gggtcttctt tggcgttatt gtagtctcgt caggaggggt tctatccaac 540

atgcccctga ctcaggatga ggcagaggag ctcatgtaca ggttctgcat agccaatgag 600

atctacacca aggctagatc tatggatgca gacattgagc tacagaagag tgaagaagag 660

cttgaggcta ttagcagggc actgtcattc ttcagtttgt ttgagcctaa cattgaaaaa 720

gtggaaggaa cattccccaa ttcagaaatc gagatgctgg aacagtttct ttcaacacca 780

gctgatgttg acttcatcac taagacactc aaagcaaaag aggtggaggc ctatgctgat 840

ctttgtgaca gccactacct aaagcctgaa aaaaccattc aggagcggct agagatcaat 900

agatgtgagg ctattgataa aactcaggac ctcctagcta gcctgcatgc aaggagcaac 960

aaacaaacat cactgaatcg agggacagtc aaactcccgc cctggctacc aaagccatca 1020

agtgagtcaa tagacatcaa gaccgactca ggctttggtt ccttaatgga ccatggcgca 1080

tatggtgagc tgtgggcaaa gtgccttcta gatgtctcgc tgggcaatgt ggagggggta 1140

atcagtgacc ctgcaaaaga acttgacatt gctatctctg atgatccaga aaaagatacc 1200

cccaaagaag caaagataac ctataggcga ttcaagcctg ccttaagttc aagtgcccgt 1260

caggaatttt ctctccaagg agtggaggga aagaagtgga agagaatggc agcaaaccag 1320

aagaaagaga aggagtccca tgaggcattg agccccttct tggatgttga ggacattggg 1380

gatttcctaa cattcaacaa tcttcttgca gattcaaggt atggagatga gtccgtccag 1440

agagctgtgt caatcctgtt ggagaaggca tctgccatgc aaaacacaga gctaactcat 1500

gccctcaatg actcattcaa gaggaaccta agcagtaatg tggttcagtg gtccctctgg 1560

gtctcctgtt tagcacagga gctagctagt gctctgaagc agcactgcag ggctggtgag 1620

ttcatcatca agaagttgaa gttctggcct atctatgtca tcatcaagcc gaccaaatcg 1680

tcttcccata tcttctacag cttagggatc cgcaaggctg atgtgacaag gaggctcact 1740

ggcagagtct tctctgacac cattgatgct ggggaatggg agctaacaga gttcaaaagc 1800

ctgaagacat gcaagctcac gaaccttgtc aacttaccat gcaccatgct gaactcaata 1860

gctttctgga gagagaagct gggcgtggct ccatggctgg ttcggaagcc ttgttcagag 1920

ctcagagagc aggtgggcct gaccttcctg atcagtctgg aggacaagtc taagactgag 1980

gagatcatca ccttgacaag gtacacccag atggagggct ttgtctctcc tcccatgctg 2040

cctaagcccc aaaagatgct agggaaactg gatggacctt tgagaactaa gttacaggta 2100

tacctcctca ggaagcatct ggattgcatg gtgcgaattg cttctcagcc attcagccta 2160

atccctagag aggggagggt agaatgggga ggaacattcc atgccatctc aggccggtcc 2220

acaaaccttg agaatatggt gaacagctgg tacattgggt actacaagaa caaagaggag 2280

tcaacagagc taaatgctct cggagaaatg tataagaaga ttgtagagat ggaagaggac 2340

aagcccagta gccctgagtt tctagggtgg ggggacactg attcccctaa gaagcatgaa 2400

ttctcacgga gcttcctcag agctgcttgc tcatctctgg agagagaaat tgctcagcga 2460

catggaagac aatggaagca gaaccttgag gagcgtgtcc tgagagagat tgggaccaag 2520

aacatcctgg accttgcatc catgaaggct acaagcaact tttccaaaga ctgggagctc 2580

tactcagagg tccagaccaa agagtaccat aggtccaaac tgctggagaa gatggccaca 2640

ttgatagaga agggggttat gtggtacatt gatgctgtgg gccaggcatg gaaggcagtt 2700

ctagatgacg ggtgcatgcg aatctgtctc ttcaaaaaga atcagcatgg tggtctcaga 2760

gagatctacg ttatggatgc aaatgcccgg ctcgtgcagt ttggggttga gaccatggct 2820

aggtgtgtct gtgagttgag cccacatgag actgttgcca accctagact caagaattcc 2880

atcatagaga accatgggct gaagtcagcc cgtagtcttg gtcctggctc tataaacata 2940

aactcatcca atgacgccaa gaagtggaat caggggcact acacaacaaa gctagctcta 3000

gttctttgtt ggttcatgcc agccaaattc cacagattca tttgggccgc catttccatg 3060

tttcggagaa aaaagatgat ggtggaccta aggtttttag ctcacctcag ttctaaatct 3120

gagtctaggt catctgaccc gtttagggaa gcaatgacag acgctttcca tggtaatagg 3180

gaagtctcat ggatggacaa agggcgaact tacataaaga cagagacagg aatgatgcag 3240

ggcatactgc actttacatc cagcctcctt cactcttgtg ttcagagctt ttacaagtct 3300

tatttcgtct cgaagcttaa ggagggctac atgggggaaa gcatcaatgg ggtggtggat 3360

gtcatagaag gctctgacga ctctgcgatc atgatcagca tacgccctaa gtcagacatg 3420

gatgaagtcc gatcaaggtt ctttgttgct aacttgctcc actctgtcaa gttcttgaac 3480

cctttgtttg gtatttactc atcagagaaa tcaacagtga acacagtgta ttgtgttgag 3540

tataactctg aattccactt ccacaggcac ttggtcagac ccacactgag atggatagca 3600

gcgtctcacc aaatctcaga gactgaagcc cttgcaagca ggcaagagga ttactccaac 3660

cttctaaccc agtgcttgga aggaggggcc tcattctctc ttacctacct tatacagtgc 3720

gctcagctcc tgcaccacta catgctccta ggactatgct tacatccctt gtttggaact 3780

ttcatgggga tgctgatatc agacccagat ccagccctag ggttcttcct catggacaac 3840

cctgcattcg cagggggagc aggatttagg ttcaatctgt ggagggcctg caagactaca 3900

gaccttgggc ggaagtatgc atattatttt aatgagatac agggtaaaac aaagggagat 3960

gaggattaca gagctctgga cgccacatcg ggaggaactc tcagccactc tgtcatggtg 4020

tactgggggg acaggaagaa gtatcaggcc ttattgaaca ggatgggcct tcctgaagac 4080

tgggtggagc agatagatga gaatcctgga gtcctttaca ggagagctgc caacaaaaag 4140

gaactactct taaaactggc agagaaggtt cattcaccag gtgtgactag cagcctgagt 4200

aaagggcatg tagtgcctcg ggtggtggca gcaggagtat accttctctc acgccactgc 4260

tttcgcttta gctcaagtat ccatggaagg ggctcagcac agaaggctag tcttataaaa 4320

ctgctgatga tgtcttctat ttctgccatg aagcacgggg gctcactaaa ccctaatcag 4380

gagcgaatgc tcttccctca ggcccaggag tatgacagag tatgcacatt gcttgaggaa 4440

gttgagcacc taacagggaa atttgttgtt agggagagaa acattgtcag gagccgtata 4500

gacttgttcc aagagccagt ggacttgcgg tgcaaggcag aagatctggt gtcagaggtg 4560

tggtttggcc tgaaaaggac taagcttgga ccccgtctcc tcaaggaaga gtgggacaaa 4620

cttagggcct catttgcatg gctgagcaca gacccatctg aaacattgag ggatggccct 4680

tttcttagcc atgtgcagtt tagaaacttc atagcccatg ttgatgccaa atcaagatca 4740

gtcaggctcc taggtgcccc cgtaaagaag tcaggtgggg tcaccactat aagccaagta 4800

gtcaggatga acttcttccc tggttttagc ctagaagctg agaagagctt agacaatcag 4860

gaaagacttg agagcatctc catcctcaag catgtcttgt tcatggtctt gaatggccca 4920

tacactgagg agtacaagct ggaaatgatc atagaggcct tctctactct tgtgatacct 4980

cagccatcag aggtcatcag gaaatcaagg accatgactt tatgcctctt atcgaattac 5040

ttgtctagta ggggtgggtc cattctagac cagattgaga gggcacagtc aggcactcta 5100

gggggcttca gcaagcccca gaagacattc attaggccag gaggtggtat tggctacaag 5160

ggaaaaggtg tgtggactgg agtgatggag gacacccatg ttcaaatctt gatagatgga 5220

gatgggacta gtaactggct tgaggagatc aggctcagta gtgatgccag gctttatgat 5280

gtcattgaat ccatccgaag gttatgtgac gaccttggga tcaataacag ggtggcatct 5340

gcatatagag gtcattgcat ggttaggctg agtgggttca agatcaagcc agcatcaagg 5400

actgacggct gtccagtcag gattatggaa aggggcttca ggatcaggga acttcaaaac 5460

ccagatgagg tcaagatgag agtgaggggt gacatcctca acctttcagt caccatacaa 5520

gaaggaaggg tcatgaacat tctaagctac aggcctagag acactgatat atcagagtca 5580

gccgcagcat acctctggag caatcgagac ctcttctcct ttgggaagaa ggagccatcc 5640

tgcagctgga tctgcttgaa aactcttgac aattgggcct ggtcacatgc ctcagttctc 5700

ctggcaaatg ataggaagac ccaaggcatt gataatagag ccatggggaa cattttcagg 5760

gactgtctcg agggctctct tagaaagcag gggctgatga ggtcaaaact cacagagatg 5820

gtggagaaga atgttgttcc tttaacaact caagagcttg tcgacatctt ggaggaggac 5880

atagactttt cagatgtcat agctgtggag ctctcagagg gatcacttga cattgaatcc 5940

atctttgatg gggcacctat cttgtggtct gctgaggtgg aagagttcgg ggaaggagtg 6000

gtggctgtga gctattccag taagtactat catctaaccc tgatggatca ggctgccatc 6060

acaatgtgtg cgatcatggg taaggaaggc tgtagagggc tccttactga gaagagatgc 6120

atggcagcca tacgagagca ggtacggcca ttcctcatat tcctgcaaat tcctgaggac 6180

agcatttctt gggtatctga tcagttctgt gactccaggg gtcttgatga agagagcacc 6240

attatgtggg gttga 6255

<210> 6

<211> 3222

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 M基因

<400> 6

atgatgaaag tcatctggtt ctcctctctg atctgcttag tcattcaatg cagtggggac 60

acgggcccaa tcatatgcgc agggcccatc cactcaaaca agagtgccga cataccccac 120

ctgcttggtt actctgagaa gatttgtcag atagatcggc tgatacatgt ttcgtcatgg 180

ctgagaaacc attcacaatt tcagggctac gtggggcagc gaggtggacg ctctcaggtg 240

agttacttcc cagctgaaaa ctcttactca aggtggagtg ggcttctaag cccctgtgat 300

gctgattggc ttgggatgct tgtcgtgaag aaggccaagg ggtctgatat gatagttcct 360

gggccttcat acaagggaaa agtctttttt gaacggccaa cttttgatgg atatgttggc 420

tggggctgtg gcagtgggaa gtcaaggact gagtcaggag agctctgcag ctcagactca 480

gggaccagtt ccggtcttct gccctcaaat agggttctct ggataggtga tgttgcttgc 540

cagcctatga cacccatccc tgaagagaca tttctggagc tgaagagttt tagccagagt 600

gaatttccag atatatgcaa aattgatggc attgtgttca accagtgtga gagtgagagc 660

ctacctcagc cctttgatgt tgcttggatg gatgttggcc actctcataa aatcatcatg 720

agggagcaca agaccaaatg ggtacaagag agctcatcta aggattttgt gtgctacaag 780

gaagggactg ggccgtgttc tgaatcagaa gaaaagactt gcaagaccag tggatcatgt 840

aggggggaca tgcagttttg caaggtggca ggttgtgaac atggggaaga gacatctgag 900

gccaaatgca gatgctcact agtgcacaag cccggggaag ttgttgtgtc atatggaggg 960

atgcgtgtca gaccaaaatg ctatggtttc tccagaatga tggcaacact agaggtgaac 1020

ccaccagagc aaaggattgg ccaatgtact ggctgccatc tagaatgcat aaatgggggt 1080

gtgaggataa tcactctaac tagtgagctc aagtcagcta ctgtctgtgc ttcccacttt 1140

tgtagttctg ccacaagtgg caagaaaagc acggagattc aattccactc agggtcatta 1200

gttgggaaaa cagcaattca cgtcaaaggg gcattggtgg atggaactga attcacattt 1260

gaaggcagtt gcatgttccc agatggttgt gacgcagtgg actgcacatt ctgtcgtgag 1320

tttctaaaaa atcctcagtg ctaccctgca aagaaatggt tgttcatcat tattgtcatc 1380

ctccttggat atgcaggcct catgctactc accaatgtcc ttaaggcaat cggggtttgg 1440

gggtcatggg tcatagctcc agtgaagcta atgtttgcca tcataaagaa actgatgaga 1500

tctgtgagct gcttgatggg gaaattgatg gataggggaa ggcaagtgat ccatgaagaa 1560

ataggggaga atagagaggg caaccaagat gatgttagga tcgagatggc aaggcctaga 1620

agggtaaggc actggatgta ctcacctgtc atcctgacta ttctagcaat tgggcttgct 1680

gaggggtgcg atgagatggt ccatgcagat tctaaacttg tttcgtgcaa gcaagggagc 1740

ggaaatatga aggaatgtgt cacaactggg agggcgctcc ttcctgcggt gaacccaggg 1800

caagaggcat gtctgcactt cacagcacca gggagtccgg actcaaaatg tctcaaaatc 1860

aaagttaaga ggatcaacct gaaatgcaag aagtcatcat catatttcgt tcctgatgct 1920

cggtccaggt gtacatctgt gaggagatgc cgctgggcag gagactgtca gtctgggtgc 1980

ccctctcatt tcacgtccaa ctccttttct gacgattggg caggtaaaat ggacagggct 2040

ggtctaggat tcagtgggtg ctctgatgga tgtggaggag cagcctgcgg ctgctttaat 2100

gcggcccctt catgcatctt ctggaggaaa tgggtagaga atccacatgg gatcatctgg 2160

aaagtatctc catgtgctgc atgggtccca tcagcagtca tagagcttac aatgccctcg 2220

ggggaagtga ggacattcca ccccatgagc ggcatcccta ctcaagtctt caagggtgtg 2280

agtgtgactt atttgggctc agatatggag gtatctggct tgactgatct gtgtgaaata 2340

gaagagctca agtccaagaa gctggcatta gctccctgca atcaggctgg catgggggtt 2400

gtaggcaagg ttggagagat acagtgcagt agtgaggaaa gtgcccgtac cataaaaaaa 2460

gatgggtgta tatggaatgc tgacctcgtg ggcatcgagc tacgagtgga tgacgctgtg 2520

tgctactcta agatcactag tgtggaggca gttgcaaact actctgccat acccaccact 2580

attgggggac tgaggtttga gagaagccat gacagccagg gcaaaatatc tggtagcccc 2640

ttggacatca cagccataag agggtctttt tcagttaact atagaggcct tcgactgagc 2700

ctctcagaaa ttactgctac ttgcacaggg gaggtgacaa atgtgagtgg gtgttactct 2760

tgcatgacag gcgccaaagt ctccatcaaa ctgcatagca gcaaaaatag cactgcacat 2820

gtaaggtgca aaggggatga gactgcgttc agtgtcctgg agggagttca tagctatact 2880

gtcagcctca gttttgacca tgcagtggtc gatgagcagt gccagctgaa ctgtgggggg 2940

catgagagcc aagtgactct aaaaggcaac ctcatcttcc tggatgtccc aaaattcgta 3000

gatggcagct acatgcagac atatcatagc tctgtaccca caggagcaaa tatcccaagc 3060

ccaacagact ggctgaatgc cctgtttggc aatgggctga gtaggtggat tctgggggtg 3120

ataggggttc tactgggggg attagctctc tttttcctaa tcatgtcttt gttcaaactg 3180

ggaacaaaac aggtatttcg atcaaggacg aagctggctt ag 3222

<210> 7

<211> 738

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 NP基因

<400> 7

atgtcagagt ggtccaggat tgcagtggag tttggtgagc agcagctcaa tttgactgag 60

cttgaagatt ttgcgagaga gctggcctat gaaggccttg atcctgcatt gatcatcaag 120

aagctgaagg agacaggtgg agatgattgg gtgagggaca caaagttcat cattgtcttt 180

gccctgactc gaggcaacaa gatcgtcaag gcatcaggga aaatgtcaaa ctctgggtct 240

aagaggttga tggcactcca agagaaatat gggctggttg agagggcaga aaccaggctc 300

tcaatcactc ctgtgagggt tgcacagagc cttcccactt ggacatgtgc tgcagcagca 360

gccctaaagg agtatctccc agtggggcca gctgtcatga acctgaaggt cgaaaattat 420

ccccctgaga tgatgtgcat ggcctttggg tccctgattc caactgcagg ggtatctgaa 480

gccacaacga agaccctgat ggaggcctac tctctgtggc aagatgcctt caccaagact 540

atcaatgtaa agatgcgcgg agccagcaag acagaggttt acaactcttt cagggatcct 600

ctccatgctg ctgtgaactc tgtcttcttt cccaatgatg tccgggtgaa gtggctgaag 660

gccaagggaa tccttggccc agatggggtc cccagcagag ctgctgaggt tgctgccgct 720

gcttacagaa acctgtaa 738

<210> 8

<211> 882

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 NS基因

<400> 8

atgtcgctga gcaaatgctc caacgttgac ctcaaatctg ttgcaatgaa tgccaacact 60

gtcaggcttg agccatctct aggagagtac cccactctta ggagagacct cgttgaatgc 120

tcttgtagtg tgttgactct atcaatggtc aagaggatgg gcaagatgac caacacagta 180

tggctatttg gcaacccaaa gaatcctctt caccagcttg agcctggact cgagcagctg 240

ttagacatgt actacaagga catgaggtgc tactcccaga gagagctgag tgctcttagg 300

tggcctagtg ggaagccatc tgtatggttc ctacaggcag ctcacatgtt cttctccatc 360

aagaacagct gggcaatgga aaccggtaga gagaactggc ggggcctctt ccacaggata 420

acaaaaggcc aaaagtatct ttttgaaggg gacatgatat tggattctct tgaggccata 480

gagaagcgaa ggcttagact agggttacct gagatcctaa taactgggct atccccaatt 540

ctggatgtgg ccctcctcca gatagagtca cttgcaaggc taagaggaat gagcttgaac 600

caccacttat tcacttcttc ctcattgcgt aagcctctat tagactgttg ggacttcttt 660

attcccatcc gcaaaaagaa gacagatggc tcatacagtg tcctggatga ggatgatgag 720

cctgggatcc ttcaaggtta tccatatctg atggcacact atttgaatag gtgcccattc 780

cacaacctca tcaggtttga tgaagagctg agaactgcag ccctaaacac catctgggga 840

agagattggc cagccattgg tgacctcccg aaggaggtct aa 882

<210> 9

<211> 6255

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-3 L基因

<400> 9

atgaacttgg aagtgctttg tggtaggata aacgtggaga atgggctgtc tcttggagaa 60

ccaggcctgt acgaccaaat ctacgacagg ccagggctgc cagacctaga tgtgactgtc 120

gatgccatag gtgtgacagt ggacataggg gctgtgccag actcagcatc acaactgggt 180

tcatcaatca atgctgggtt gatcacaatc cagctctctg aagcatataa gatcaatcat 240

gatttcacgt tttctggcct gtcaaagaca acagaccgac gcctctcaga ggtattcccc 300

attacacatg atggttctga tgggatgacc cctgatgtga tccacaccag attggatgga 360

accattgtgg tggttgaatt ttcaactact aggagccata acattggggg tctggaggca 420

gcatacagga caaagataga aaaatatagg gaccctatct caaggcgtgt tgatatcatg 480

gagaacccga gggtcttctt tggcgtcatt gtggtctcgt cagggggagt tctgtccaac 540

atgcccctga ctcaggatga ggcagaggag ctcatgtaca ggttctgcat agccaatgag 600

atctacacta aggctaggtc tatggatgca gacattgagc tgcagaagag cgaagaagag 660

cttgaggcta ttagcagggc actatcattc ttcagtttgt ttgagccaaa cattgaaaga 720

gtggaaggaa cattccctaa ttcggaaatc gagatgctgg aacagtttct ctcaactcca 780

gctgatgttg acttcatcac caagaccctc aaagcaaaag aggtggaggc ctatgctgat 840

ctttgtgaca gccactatct aaagcctgaa aaaaccattc aggagcggct agagatcaat 900

agatgtgagg ctattgacaa gactcaggac ctcctagcta gcctgcatgc aaggagcaac 960

aagcaaacat cattgaatcg agggacagtc aagctcccgc cctggctacc aaagccatca 1020

agtgagtcaa tagacatcaa gactgactca ggctttggtt ccttaatgga tcatggcaca 1080

tatggagagc tgtgggcaaa gtgcctccta gatgtctcgc tgggcaatgt ggagggggta 1140

gtcagtgacc ctgcaaaaga acttgacatt gctatctctg atgatccaga aaaagatacc 1200

cccaaagagg caaagataac ctataggcgg ttcaagcctg ccttgagctc aagtgcccgt 1260

caagaatttt ctctccaagg agtggagggg aagaagtgga agagaatggc agcaaaccag 1320

aagaaagaga aggagtccca tgagacattg agccctttct tggatgttga agacattggg 1380

gatttcctaa cattcaacaa tcttctcgca gattcgaggt atggagatga gtccgtccag 1440

agagctgtgt caatcttgtt ggaaaaggca tctgccatgc aagacacaga gctcactcat 1500

gccctcaacg actcattcaa gaggaaccta agcagcaatg tggttcagtg gtccctttgg 1560

gtctcctgtc tagcacaaga gctagctagt gctctgaagc agcactgcag ggctggtgag 1620

ttcatcatca agaagctgaa gttctggcct atctatgtca ttatcaagcc gaccaaatcg 1680

tcatcccata tcttctacag cttagggatc cgcaaggctg atgtgacaag gaggctcact 1740

ggcagagtct tctctgacac cattgatgct ggggaatggg agctaacaga gttcaagagc 1800

ctgaagacat gcaagctcac caaccttgtc aacttgccat gcaccatgct gaactcaata 1860

gctttctgga gagagaagct gggcgtggct ccatggctgg ttcggaagcc ttgttcagag 1920

ctcagagagc aggtgggcct gaccttcttg atcagtttgg aggacaagtc taagactgag 1980

gagatcatca ccttgacaag gtacactcaa atggagggct tcgtctctcc tcctatgctg 2040

cctaagcccc aaaagatgct agggaaactg gatgggcctt tgagaactaa gctacaggta 2100

tacctcctca ggaagcatct ggattgcatg gtgcgaattg cttcccagcc attcagcctg 2160

atccctagag aggggagggt agaatgggga gggacattcc atgccatctc aggccggtcc 2220

acaaaccttg agaatatggt gaacagctgg tacattgggt actacaagaa caaagaggag 2280

tcaacagagc taaatgctct tggagaaatg tataagaaga ttgtggagat ggaagaggac 2340

aagcccagca gccctaagtt tctagggtgg ggggacactg attcccctaa gaagcatgaa 2400

ttctcacgga gcttcctcag agctgcttgc tcatctctgg agagagaaat tgctcagcga 2460

catggaagac aatggaagca gaaccttgag gagcgtgtcc tgagagagat tggaaccaag 2520

aacatcctag accttgcatc catgaaggct acaagcaact tttccaaaga ctgggagctc 2580

tactcagaag tccagaccaa agagtaccat aggtccaaat tgctggagaa gatggccaca 2640

ttgattgaga agggggttat gtggtacatt gatgctgtgg gccaggcttg gaaggcagtt 2700

ctagatgacg ggtgcatgcg aatctgtctc ttcaaaaaga atcagcatgg tggcctcaga 2760

gagatctacg ttatggatgc aaatgcccgg ctcgtgcagt ttggggttga gaccatggct 2820

aggtgtgtct gtgagctgag cccacatgag actgttgcca atcctaggct taagaattcc 2880

atcatagaga accatgggct gaagtcagcc cgtagccttg gccctggctc tataaacata 2940

aactcatcca atgatgccaa gaagtggaat caggggcact acacaacaaa gctagctcta 3000

gttctttgtt ggttcatgcc agccaaattc cacagattca tttgggctgc catttccatg 3060

tttcggagaa aaaagatgat ggtggaccta aggtttttag ctcacctcag ttctaaatct 3120

gagtccaggt catctgatcc atttagggaa gcaatgacag acgcattcca tggaaatagg 3180

gaagtctcat ggatggacaa ggggcgaact tacataaaga cagagacagg gatgatgcag 3240

ggcatactgc actttacatc cagcctcctc cactcttgtg ttcagagttt ttacaagtct 3300

tatttcgtct cgaagctcaa ggagggctac atgggggaaa gcatcagtgg ggtggtggat 3360

gtcatagaag gttctgacga ctcagcgatc atgatcagca tacgccctaa gtcagatatg 3420

gatgaagtcc gatcaaggtt ttttgttgct aacctgctcc actctgtcaa attcttgaac 3480

cctttgtttg ggatttactc atcagagaag tcaacagtga acacagtgta ttgtgtcgag 3540

tataactctg aattccattt ccacaggcac ttggttagac ccacactgag atggatagca 3600

gcgtctcacc aaatctcaga gactgaagcc cttgcaagca ggcaagagga ttactccaac 3660

cttctaaccc agtgcttgga aggaggggcc tcattctctc ttacctacct catacagtgc 3720

gctcagctcc tacaccacta catgcttcta ggactatgct tgcatccctt gtttggaacc 3780

ttcatgggga tgctgatatc agacccagat cctgccctag gattcttcct catggacaac 3840

cctgcattcg caggaggagc aggatttaga ttcaatctgt ggagagcctg caagaccaca 3900

gaccttgggc ggaagtatgc atattacttc aatgagatac agggtaaaac aaagggagat 3960

gaggactaca gagctctgga cgccacatcg ggaggaactc tcagccactc tgttatggtg 4020

tactgggggg acaggaagaa gtatcaggcc ttattgaaca ggatgggcct tcctgaagac 4080

tgggtggagc agatagatga gaatcctgga gtcctttaca ggagagctgc caacaagaag 4140

gaactactct taaaactggc agagaaggtt cattcacctg gtgtgactag cagcctgagt 4200

aaagggcatg tagtgcctcg ggtggtggca gcaggagtat accttctctc acgccactgc 4260

tttcgcttta gctcaagcat ccatggaagg ggctcagcac agaaggctag tctcataaaa 4320

ctgctgatga tgtcttctat ttctgccatg aaacacgggg gctcattaaa ccccaatcag 4380

gagcgaatgc tcttccctca ggctcaagag tatgatagag tatgcacatt gcttgaggaa 4440

gttgaacacc taacagggaa atttgttgtt agggagagaa acattgtcag gagccgcata 4500

gacttgttcc aagagccagt tgacttgcgg tgtaaggcag aagatctggt gtcagaggtg 4560

tggtttggcc tgaaaaggac taagcttgga ccccgtctcc tcaaggaaga gtgggacaaa 4620

cttagggcct catttgcatg gctgagcaca gacccatctg aaacattgag ggatggtcct 4680

tttcttagcc atgtgcagtt taggaacttc atagcccacg ttgatgccaa atcaagatca 4740

gtcaggctcc taggtgcccc cgtgaagaag tcaggtgggg taaccaccat aagccaagta 4800

gtcagaatga acttcttccc tggttttagc ctagaagctg agaagagctt agacaatcag 4860

gagagacttg agagcatctc catcctcaag catgtcttgt tcatggtctt gaatggccca 4920

tacactgagg agtacaagct ggacatgatc atagaggcct tctctactct tgtgatacct 4980

cagccatcag aggtcatcag gaaatcaagg accatgactt tatgcctctt atcgaattac 5040

ttgtctagta ggggtgggtc cattctagac cagattgaga gggcacagtc aggcactcta 5100

gggggattca gcaagcccca gaagacattc atcaggccag gaggtggtat tggctacaag 5160

ggaaaaggtg tgtggactgg agtgatggag gacacccatg ttcaaattct gatagatgga 5220

gatgggacta gcaactggct tgaggagatc aggctcagta gtgatgccag gctttatgat 5280

gtcattgaat ccatccggag gttatgtgat gaccttggga tcaacaacag ggtggcatcg 5340

gcatataggg gtcattgcat ggttagactg agtggattca agatcaagcc agcatcaagg 5400

actgacggct gtccagttag gattatggaa aggggcttca ggatcagaga gcttcaaaac 5460

ccagatgagg tcaagatgag agtgaggggt gacattctca acctctctgt taccatacaa 5520

gaaggaagag tcatgaacat tctgagctac aggccgagag acactgatat atcagagtca 5580

gcagcagcat acctatggag caatcgagac ctcttctcct ttgggaagaa ggagccatcc 5640

tgcagctgga tctgcttgaa aactcttgac aattgggcct ggtcacatgc ctcagttctc 5700

ctggcaaatg ataggaagac ccaaggcatt gataatagag ctatggggaa cattttcagg 5760

gactgtctcg agggttccct cagaaagcaa gggctgatga ggtcaaagct cactgagatg 5820

gtggagaaga atgtggttcc tttaacaact caagagcttg tcgatatcct ggaggaggat 5880

atagactttt cagatgtcat agctgtggag ctctcagagg gatcacttga cattgagtcc 5940

atctttgatg gagcacctat cttgtggtct gctgaggtgg aagagtttgg agaaggagtg 6000

gtagctgtga gctattccag taagtactat catctaaccc tgatggacca agctgccatc 6060

acaatgtgtg cgatcatggg taaggagggc tgtagagggc tcctcactga gaagagatgc 6120

atggcagcca tacgagagca ggtaaggcca ttcctcatat tcctgcaaat ccctgaggac 6180

agcatttctt gggtgtctga tcagttctgc gactccaggg gtcttgatga agagagcacc 6240

attatgtggg gttaa 6255

<210> 10

<211> 3222

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-3 M基因

<400> 10

atgatgaaag tcatctggtt ctcctctctg atctgcttag tcattcaatg cagtggggat 60

acgggcccaa tcatatgcgc tgggcccatc cactcaaaca agagcgccaa cataccccac 120

ctgcttggtt actctgagaa aatttgtcag atagatcggc ttatacatgt ttcgtcatgg 180

ctgagaaacc attcacaatt tcagggctac gtggggcagc gaggtggacg ctctcaggtg 240

agttactacc cagctgaaaa ctcttactca aggtggagtg gacttctaag cccctgtgat 300

gctgattggc ttgggatgct tgtcgtgaag aaggccaagg ggtctgatat gatagttcct 360

gggccttcat acaaagggaa agtcttcttt gaacggccaa cttttgatgg atatgtgggc 420

tggggctgtg gtagtgggaa gtcaaggaca gagtcaggtg agctctgcag ctcagactca 480

gggaccagtt ctggtctact gccctcaaat agggttctct ggataggtga tgttgcttgc 540

cagcctatga cacccatccc tgaggagaca tttctggagc tgaagagttt tagccagagt 600

gaattcccag acatatgcaa agttgatggc attgtgttca accagtgtga gagtgagagt 660

ctacctcagc cctttgatgt tgcatggatg gatgtaggcc actctcataa aatcatcatg 720

agggagcaca agaccaaatg ggtacaagag agctcatcta aggattttgt gtgctacaag 780

gaagggactg ggccgtgttc tgaatcagaa gaaaagactt gcaagaccag tggatcatgc 840

aggggggaca tgcagttttg caaggtagca ggttgtgaac atggggaaga ggcatctgaa 900

gccaaatgta gatgctcact agtgcacaag cccggggaag ttgttgtgtc atatggaggg 960

atgcgtgtca gaccaaagtg ttatggtttc tccagaatga tggcaacact agaggtgaac 1020

ccaccagagc aaagaattgg ccaatgcact ggctgccatc tagaatgcat aaatgggggt 1080

gtgaggctaa ttactctaac tagtgagctc aagtcagcta ctgtctgtgc ttcccacttt 1140

tgtagttctg ctacaagtgg caagaaaagc acggagattc aattccactc agggtcatta 1200

gttgggaaag cagcaattca cgtcaaaggg actttggtgg atggaactga attcacattt 1260

gagggcagtt gcatgttccc agatggttgt gacgcagtgg actgcacatt ctgtcgcgag 1320

ttcctaaaaa atcctcagtg ctaccctgca aagaaatggt tgttcataat tattgccatc 1380

ctccttggat atgcaggcct catgctgctc accaatgttc ttaaggcaat cggggtttgg 1440

ggatcatggg tcatagctcc agtgaagctg atgtttgcca tcataaagaa actgatgaga 1500

tctgtgagct gcttgatggg gaaattaatg gataggggaa ggcaagtgat tcatgaagaa 1560

ataggggaga atagagaggg caaccaagaa gatgttagaa ttgagattgc aagacccaga 1620

agggtgaggc attggatgta ctcacctgtc atcctggcta ttctagcaat tgggcttgct 1680

gagggctgcg atgagatggt ccatgcagat tcaaaacttg tttcgtgcag gcaagggagc 1740

ggaaatatga aggaatgtgt cacaactggg agggcgcttc ttcctgcggt gaacccagga 1800

caagaggcat gtctgcactt cacggcacct ggaagtccgg actcaaaatg tctcaagatc 1860

aaggttaaga ggatcaacct aaaatgtaag aagtcatcat catattttgt tcctgatgct 1920

cggtccagat gtacgtctgt gaggagatgt cgctgggcag gagactgtca gtctgggtgc 1980

ccctctcatt tcacgtccaa ctccttctct gatgattggg caggtaaaat ggacagggct 2040

ggtctaggat tcagtgggtg ctctgatgga tgtggaggag cagcctgcgg ctgctttaat 2100

gcggcccctt catgcatctt ttggaggaaa tgggtagaga atccacatgg gatcatctgg 2160

aaagtatctc catgtgctgc atgggtccct tcaacagtca tagagctaac aatgccctcg 2220

ggggaagtga ggacattcca ccccatgagc ggcatcccca cacaagtctt caagggtgtg 2280

agtgtgactt acttaggctc agatatggag gtgtctggcc tgactgacct gtgtgagata 2340

gaagagctca agtccaagaa gctggcatta gctccctgca atcaggctgg catgggagtt 2400

gtgggcaagg ttggagagat acagtgcagt agcgaggaaa gcgcccgttc cataaagaaa 2460

gatgggtgta tatggaatgc tgaccttgtg ggcatagagc tacgagtgga tgacgcagtg 2520

tgctattcta agatcactag tgtggaggca gttgcaaact actctgccat acccaccact 2580

attggggggt tgaggtttga gagaagccat gacagccagg gtaaaatatc tggtagcccc 2640

ctagacatta cagccataag agggtctttt tccgttaatt atagaggcct tcgactgagc 2700

ctctcagaaa tcactgctac ttgcacagga gaggtgacga atgtgagtgg gtgttactct 2760

tgcatgacag gcgccaaagt ctccatcaaa ctgcatagca gcaaaaatag cactgcccat 2820

gtaagatgca aaggggatga gaccgcattc agtgtcctgg agggagttca tagctatact 2880

gtcagtctta gctttgacca tgcagtggtc gatgagcagt gccagctgaa ctgtgggggg 2940

catgagagtc aagtgactct aaaaggcaac ctcatcttcc tggatgtccc aaaatttgta 3000

gatggcagct atatgcagac atatcatagt tctgtgccca caggggctaa tatcccaagc 3060

cctacagact ggctgaatgc cttgtttggc aatgggctga gtaggtggat tcttggggta 3120

ataggggttc tactgggggg attggctctc ttcttcttaa ttatgtcctt gttcaaactg 3180

ggaacaaaac agatattccg atcaaggacg aagctggctt ag 3222

<210> 11

<211> 738

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-3 NP基因

<400> 11

atgtcagagt ggtccaggat tgcagtggag tttggtgagc agcagctcaa tttgactgag 60

cttgaggatt tcgcgagaga gctagcctat gaaggccttg atcctgcctt gataatcaag 120

aagctgaagg agacaggtgg agatgattgg gtgagagata caaagttcat cattgtcttt 180

gccctgaccc gaggcaacaa gatcgtcaag gcatcaggga aaatgtcaaa ctcagggtct 240

aagaggttga tggcacttca agagaaatat ggactggttg agagggcaga aaccaggctc 300

tcaatcactc ctgtgagggt agcacagagc cttcccactt ggacgtgcgc tgcagcagca 360

gccttaaagg agtatctccc agtgggccca gctgtcatga acctgaaggt cgaaaattac 420

cccccagaga tgatgtgcat ggcctttggg tctctgattc caactgcagg ggtatcagaa 480

gccacaacga agaccctgat ggaggcctac tctctgtggc aagatgcctt caccaagact 540

attaatgtga agatgcgtgg agccagcaag acagaggttt acaactcctt cagagatccc 600

ctccatgctg ctgtgaactc tgtcttcttt cccaatgatg ttcgggtgaa gtggctgaag 660

gccaagggaa tcctaggccc agatggggtc cccagcagag ctgctgaggt tgctgctgct 720

gcttacagaa acctgtaa 738

<210> 12

<211> 882

<212> DNA

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-3 NS基因

<400> 12

atgtcgctga gcaaatgctc caacgttgac ctcaaatctg tagcaatgaa tgccaacact 60

gttaggcttg aaccatctct aggagagtac cccactctta ggaaagacct cgttgaatgc 120

tcttgtagtg tgttgactct atcaatggtc aagaggatgg gcaagatgac caacacagta 180

tggttatttg gcaacccaaa aaatcctctt caccagcttg agcctggact tgagcagctg 240

ttggatatgt actacaagga catgaggtgc tactcccaga gagagctgag tgccctcagg 300

tggcctagtg ggaagccttc tgtatggttc ctacaggcag ctcacatgtt cttttccatc 360

aagaacagct gggcaatgga aaccggtaga gagaactggc ggggcctctt ccacaggata 420

acaaaaggca aaaagtatct ttttgaaggg gacatgatat tggattctct tgaagccata 480

gagaagcgaa ggctcagact tgggttacct gagatcctaa taactggact atccccaatt 540

ctggatgtgg ccctcctcca gatagagtca cttgcaaggc taagaggcat gagcttgaac 600

caccacttat tcacttcttc ctcactgcgt aagcctctgt tagattgttg ggacttcttt 660

attcctatcc gcaaaaagaa gacagatggc tcatacagtg ttttggatga ggatgatgag 720

cctggggtcc ttcaaggtta cccatatctg atggcacact atctgaacag gtgcccattc 780

cacaacctca tcagatttga tgaagaactg agaactgcag ccctgaacac catctgggga 840

agagattggc cggccattgg tgacctcccg aaggaggtct aa 882

<210> 13

<211> 2085

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 L

<400> 13

Met Asp Leu Glu Val Leu Cys Gly Arg Ile Asn Val Glu Asn Gly Leu

1 5 10 15

Ser Leu Gly Glu Pro Gly Leu Tyr Asp Gln Ile Tyr Asp Arg Pro Gly

20 25 30

Leu Pro Asp Leu Asp Val Thr Val Asp Ala Thr Gly Val Thr Val Asp

35 40 45

Ile Gly Ala Val Pro Asp Ser Ala Ser Gln Leu Gly Ser Ser Ile Asn

50 55 60

Ala Gly Leu Ile Thr Ile Gln Leu Ser Glu Ala Tyr Lys Ile Asn His

65 70 75 80

Asp Phe Thr Phe Ser Gly Leu Ser Lys Thr Thr Asp Arg Arg Leu Ser

85 90 95

Glu Val Phe Pro Ile Thr His Asp Gly Ser Asp Gly Met Thr Pro Asp

100 105 110

Val Ile His Thr Arg Leu Asp Gly Thr Ile Val Val Val Glu Phe Ser

115 120 125

Thr Thr Arg Ser His Asn Ile Gly Gly Leu Glu Ala Ala Tyr Arg Thr

130 135 140

Lys Ile Glu Lys Tyr Arg Asp Pro Ile Ser Arg Arg Val Asp Ile Met

145 150 155 160

Glu Asn Pro Arg Val Phe Phe Gly Val Ile Val Val Ser Ser Gly Gly

165 170 175

Val Leu Ser Asn Met Pro Leu Thr Gln Asp Glu Ala Glu Glu Leu Met

180 185 190

Tyr Arg Phe Cys Ile Ala Asn Glu Ile Tyr Thr Lys Ala Arg Ser Met

195 200 205

Asp Ala Asp Ile Glu Leu Gln Lys Ser Glu Glu Glu Leu Glu Ala Ile

210 215 220

Ser Arg Ala Leu Ser Phe Phe Ser Leu Phe Glu Pro Asn Ile Glu Arg

225 230 235 240

Val Glu Gly Thr Phe Pro Asn Ser Glu Ile Glu Met Leu Glu Gln Phe

245 250 255

Leu Ser Thr Pro Ala Asp Val Asp Phe Ile Thr Lys Thr Leu Lys Ala

260 265 270

Lys Glu Val Glu Ala Tyr Ala Asp Leu Cys Asp Ser His Tyr Leu Lys

275 280 285

Pro Glu Lys Thr Ile Gln Glu Arg Leu Glu Ile Asn Arg Cys Glu Ala

290 295 300

Ile Asp Lys Thr Gln Asp Leu Leu Ala Gly Leu His Ala Arg Ser Asn

305 310 315 320

Lys Gln Thr Ser Leu Asn Arg Gly Thr Val Lys Leu Pro Pro Trp Leu

325 330 335

Pro Lys Pro Ser Ser Glu Ser Ile Asp Ile Lys Thr Asp Ser Gly Phe

340 345 350

Gly Ser Leu Met Asp His Gly Ala Tyr Gly Glu Leu Trp Ala Lys Cys

355 360 365

Leu Leu Asp Val Ser Leu Gly Asn Val Glu Gly Val Val Ser Asp Pro

370 375 380

Ala Lys Glu Leu Asp Ile Ala Ile Ser Asp Asp Pro Glu Lys Asp Thr

385 390 395 400

Pro Lys Glu Ala Lys Ile Thr Tyr Arg Arg Phe Lys Pro Ala Leu Ser

405 410 415

Ser Ser Ala Arg Gln Glu Phe Ser Leu Gln Gly Val Glu Gly Lys Lys

420 425 430

Trp Lys Arg Met Ala Ala Asn Gln Lys Lys Glu Lys Glu Ser His Glu

435 440 445

Thr Leu Ser Pro Phe Leu Asp Val Glu Asp Ile Gly Asp Phe Leu Thr

450 455 460

Phe Asn Asn Leu Leu Ala Asp Ser Arg Tyr Gly Asp Glu Ser Ile Gln

465 470 475 480

Arg Ala Val Ser Ile Leu Leu Glu Lys Ala Ser Ala Met Gln Asp Thr

485 490 495

Glu Leu Thr His Ala Leu Asn Asp Ser Phe Lys Arg Asn Leu Ser Ser

500 505 510

Asn Val Val Gln Trp Ser Leu Trp Val Ser Cys Leu Ala Gln Glu Leu

515 520 525

Ala Ser Ala Leu Lys Gln His Cys Arg Ala Gly Glu Phe Ile Ile Lys

530 535 540

Lys Leu Lys Phe Trp Pro Ile Tyr Val Ile Ile Lys Pro Thr Lys Ser

545 550 555 560

Ser Ser His Ile Phe Tyr Ser Leu Gly Ile Arg Lys Ala Asp Val Thr

565 570 575

Arg Arg Leu Thr Gly Arg Val Phe Ser Asp Thr Ile Asp Ala Gly Glu

580 585 590

Trp Glu Leu Thr Glu Phe Lys Ser Leu Lys Thr Cys Lys Leu Thr Asn

595 600 605

Leu Val Asn Leu Pro Cys Thr Met Leu Asn Ser Ile Ala Phe Trp Arg

610 615 620

Glu Lys Leu Gly Val Ala Pro Trp Leu Val Arg Lys Pro Cys Ser Glu

625 630 635 640

Leu Arg Glu Gln Val Gly Leu Thr Phe Leu Ile Ser Leu Glu Asp Lys

645 650 655

Ser Lys Thr Glu Glu Ile Ile Thr Leu Thr Arg Tyr Thr Gln Met Glu

660 665 670

Gly Phe Val Ser Pro Pro Met Leu Pro Lys Pro Gln Lys Met Leu Gly

675 680 685

Lys Leu Asp Gly Pro Leu Arg Thr Lys Leu Gln Val Tyr Leu Leu Arg

690 695 700

Lys His Leu Asp Cys Met Val Arg Ile Ala Ser Gln Pro Phe Ser Leu

705 710 715 720

Ile Pro Arg Glu Gly Arg Val Glu Trp Gly Gly Thr Phe His Ala Ile

725 730 735

Ser Gly Arg Ser Thr Asn Leu Glu Asn Met Val Asn Ser Trp Tyr Ile

740 745 750

Gly Tyr Tyr Lys Asn Lys Glu Glu Ser Thr Glu Leu Asn Ala Leu Gly

755 760 765

Glu Met Tyr Lys Lys Ile Val Glu Met Glu Glu Asp Lys Pro Ser Ser

770 775 780

Pro Glu Phe Leu Gly Trp Gly Asp Thr Asp Ser Pro Lys Lys His Glu

785 790 795 800

Phe Ser Arg Ser Phe Leu Arg Ala Ala Cys Ser Ser Leu Glu Arg Glu

805 810 815

Ile Ala Gln Arg His Gly Arg Gln Trp Lys Gln Asn Leu Glu Glu Arg

820 825 830

Val Leu Arg Glu Ile Gly Thr Lys Asn Ile Leu Asp Leu Ala Ser Met

835 840 845

Lys Ala Thr Ser Asn Phe Ser Lys Asp Trp Glu Leu Tyr Ser Glu Val

850 855 860

Gln Thr Lys Glu Tyr His Arg Ser Lys Leu Leu Glu Lys Met Ala Thr

865 870 875 880

Leu Ile Glu Lys Gly Val Met Trp Tyr Ile Asp Ala Val Gly Gln Ala

885 890 895

Trp Lys Ala Val Leu Asp Asp Gly Cys Met Arg Ile Cys Leu Phe Lys

900 905 910

Lys Asn Gln His Gly Gly Leu Arg Glu Ile Tyr Val Met Asp Ala Asn

915 920 925

Ala Arg Leu Val Gln Phe Gly Val Glu Thr Met Ala Arg Cys Val Cys

930 935 940

Glu Leu Ser Pro His Glu Thr Val Ala Asn Pro Arg Leu Lys Asn Ser

945 950 955 960

Ile Ile Glu Asn His Gly Leu Lys Ser Ala Arg Ser Leu Gly Pro Gly

965 970 975

Ser Ile Asn Ile Asn Ser Ser Asn Asp Ala Arg Lys Trp Asn Gln Gly

980 985 990

His Tyr Thr Thr Lys Leu Ala Leu Val Leu Cys Trp Phe Met Pro Ala

995 1000 1005

Lys Phe His Arg Phe Ile Trp Ala Ala Ile Ser Met Phe Arg Arg Lys

1010 1015 1020

Lys Met Met Val Asp Leu Arg Phe Leu Ala His Leu Ser Ser Lys Ser

1025 1030 1035 1040

Glu Ser Arg Ser Ser Asp Pro Phe Arg Glu Ala Met Thr Asp Ala Phe

1045 1050 1055

His Gly Asn Arg Glu Val Ser Trp Met Asp Lys Gly Arg Thr Tyr Ile

1060 1065 1070

Lys Thr Glu Thr Gly Met Met Gln Gly Ile Leu His Phe Thr Ser Ser

1075 1080 1085

Leu Leu His Ser Cys Val Gln Ser Phe Tyr Lys Ser Tyr Phe Val Ser

1090 1095 1100

Lys Leu Lys Glu Gly Tyr Met Gly Glu Ser Ile Asn Gly Val Val Asp

1105 1110 1115 1120

Val Ile Glu Gly Ser Asp Asp Ser Ala Ile Met Ile Ser Ile Arg Pro

1125 1130 1135

Lys Ser Asp Met Asp Glu Val Arg Ser Arg Phe Phe Val Ala Asn Leu

1140 1145 1150

Leu His Ser Val Lys Phe Leu Asn Pro Leu Phe Gly Ile Tyr Ser Ser

1155 1160 1165

Glu Lys Ser Thr Val Asn Thr Val Tyr Cys Val Glu Tyr Asn Ser Glu

1170 1175 1180

Phe His Phe His Arg His Leu Val Arg Pro Thr Leu Arg Trp Ile Ala

1185 1190 1195 1200

Ala Ser His Gln Ile Ser Glu Thr Glu Ala Leu Ala Ser Arg Gln Glu

1205 1210 1215

Asp Tyr Ser Asn Leu Leu Thr Gln Cys Leu Glu Gly Gly Ala Ser Phe

1220 1225 1230

Ser Leu Thr Tyr Leu Ile Gln Cys Ala Gln Leu Leu His His Tyr Met

1235 1240 1245

Leu Leu Gly Leu Cys Leu His Pro Leu Phe Gly Thr Phe Met Gly Met

1250 1255 1260

Leu Ile Ser Asp Pro Asp Pro Ala Leu Gly Phe Phe Leu Met Asp Asn

1265 1270 1275 1280

Pro Ala Phe Ala Gly Gly Ala Gly Phe Arg Phe Asn Leu Trp Arg Ala

1285 1290 1295

Cys Lys Thr Thr Asp Leu Gly Arg Lys Tyr Ala Tyr Tyr Phe Asn Glu

1300 1305 1310

Ile Gln Gly Lys Thr Lys Gly Asp Glu Asp Tyr Arg Ala Leu Asp Ala

1315 1320 1325

Thr Ser Gly Gly Thr Leu Ser His Ser Val Met Val Tyr Trp Gly Asp

1330 1335 1340

Arg Lys Lys Tyr Gln Ala Leu Leu Asn Arg Met Gly Leu Pro Glu Asp

1345 1350 1355 1360

Trp Val Glu Gln Ile Asp Glu Asn Pro Gly Val Leu Tyr Arg Arg Ala

1365 1370 1375

Ala Asn Lys Lys Glu Leu Leu Leu Lys Leu Ala Glu Lys Val His Ser

1380 1385 1390

Pro Gly Val Thr Ser Ser Leu Ser Lys Gly His Val Val Pro Arg Val

1395 1400 1405

Val Ala Ala Gly Val Tyr Leu Leu Ser Arg His Cys Phe Arg Phe Ser

1410 1415 1420

Ser Ser Ile His Gly Arg Gly Ser Ala Gln Lys Ala Ser Leu Ile Lys

1425 1430 1435 1440

Leu Leu Met Met Ser Ser Val Ser Ala Met Lys His Gly Gly Ser Leu

1445 1450 1455

Asn Pro Asn Gln Glu Arg Met Leu Phe Pro Gln Ala Gln Glu Tyr Asp

1460 1465 1470

Arg Val Cys Thr Leu Leu Glu Glu Val Glu His Leu Thr Gly Lys Phe

1475 1480 1485

Val Val Arg Glu Arg Asn Ile Val Arg Ser Arg Ile Asp Leu Phe Gln

1490 1495 1500

Glu Pro Val Asp Leu Arg Cys Lys Ala Glu Asp Leu Val Ser Glu Val

1505 1510 1515 1520

Trp Phe Gly Leu Lys Arg Thr Lys Leu Gly Pro Arg Leu Leu Lys Glu

1525 1530 1535

Glu Trp Asp Lys Leu Arg Ala Ser Phe Ala Trp Leu Ser Thr Asp Pro

1540 1545 1550

Ser Glu Thr Leu Arg Asp Gly Pro Phe Leu Ser His Val Gln Phe Arg

1555 1560 1565

Asn Phe Ile Ala His Val Asp Ala Lys Ser Arg Ser Val Arg Leu Leu

1570 1575 1580

Gly Ala Pro Val Lys Lys Ser Gly Gly Val Thr Thr Ile Ser Gln Val

1585 1590 1595 1600

Val Arg Met Asn Phe Phe Pro Gly Phe Ser Leu Glu Ala Glu Lys Ser

1605 1610 1615

Leu Asp Asn Gln Glu Arg Leu Glu Ser Ile Ser Ile Leu Lys His Val

1620 1625 1630

Leu Phe Met Val Leu Asn Gly Pro Tyr Thr Glu Glu Tyr Lys Leu Glu

1635 1640 1645

Met Ile Ile Glu Ala Phe Ser Thr Leu Val Ile Pro Gln Pro Ser Glu

1650 1655 1660

Val Ile Arg Lys Ser Arg Thr Met Thr Leu Cys Leu Leu Ser Asn Tyr

1665 1670 1675 1680

Leu Ser Ser Arg Gly Gly Ser Ile Leu Asp Gln Ile Glu Arg Ala Gln

1685 1690 1695

Ser Gly Thr Leu Gly Gly Phe Ser Lys Pro Gln Lys Thr Phe Ile Arg

1700 1705 1710

Pro Gly Gly Gly Ile Gly Tyr Lys Gly Lys Gly Val Trp Thr Gly Val

1715 1720 1725

Met Glu Asp Thr His Val Gln Ile Leu Ile Asp Gly Asp Gly Thr Ser

1730 1735 1740

Asn Trp Leu Glu Glu Ile Arg Leu Ser Ser Asp Ala Arg Leu Tyr Asp

1745 1750 1755 1760

Val Ile Glu Ser Ile Arg Arg Leu Cys Asp Asp Leu Gly Ile Asn Asn

1765 1770 1775

Arg Val Ala Ser Ala Tyr Arg Gly His Cys Met Val Arg Leu Ser Gly

1780 1785 1790

Phe Lys Ile Lys Pro Ala Ser Arg Thr Asp Gly Cys Pro Val Arg Ile

1795 1800 1805

Met Glu Arg Gly Phe Arg Ile Arg Glu Leu Gln Asn Pro Asp Glu Val

1810 1815 1820

Lys Met Arg Val Arg Gly Asp Ile Leu Asn Leu Ser Val Thr Ile Gln

1825 1830 1835 1840

Glu Gly Arg Val Met Asn Ile Leu Ser Tyr Arg Pro Arg Asp Thr Asp

1845 1850 1855

Ile Ser Glu Ser Ala Ala Ala Tyr Leu Trp Ser Asn Arg Asp Leu Phe

1860 1865 1870

Ser Phe Gly Lys Lys Glu Pro Ser Cys Ser Trp Ile Cys Leu Lys Thr

1875 1880 1885

Leu Asp Asn Trp Ala Trp Ser His Ala Ser Val Leu Leu Ala Asn Asp

1890 1895 1900

Arg Lys Thr Gln Gly Ile Asp Asn Lys Ala Met Gly Asn Ile Phe Arg

1905 1910 1915 1920

Asp Cys Leu Glu Gly Ser Leu Arg Lys Gln Gly Leu Met Arg Ser Lys

1925 1930 1935

Leu Thr Glu Met Val Glu Lys Asn Val Val Pro Leu Thr Thr Gln Glu

1940 1945 1950

Leu Val Asp Ile Leu Glu Glu Asp Ile Asp Phe Ser Asp Val Ile Ala

1955 1960 1965

Val Glu Leu Ser Glu Gly Ser Leu Asp Ile Glu Ser Ile Phe Asp Gly

1970 1975 1980

Ala Pro Ile Leu Trp Ser Ala Glu Val Glu Glu Phe Gly Glu Gly Val

1985 1990 1995 2000

Val Ala Val Ser Tyr Ser Ser Lys Tyr Tyr His Leu Thr Leu Met Asp

2005 2010 2015

Gln Ala Ala Ile Thr Met Cys Ala Ile Met Gly Lys Glu Gly Cys Arg

2020 2025 2030

Gly Leu Leu Thr Glu Lys Arg Cys Met Ala Ala Ile Arg Glu Gln Val

2035 2040 2045

Arg Pro Phe Leu Ile Phe Leu Gln Ile Pro Glu Asp Ser Ile Ser Trp

2050 2055 2060

Val Ser Asp Gln Phe Cys Asp Ser Arg Gly Leu Asp Glu Glu Ser Thr

2065 2070 2075 2080

Ile Met Trp Gly ***

2085

<210> 14

<211> 1074

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 M

<400> 14

Met Met Lys Val Ile Trp Phe Ser Ser Leu Ile Cys Leu Val Ile Gln

1 5 10 15

Cys Ser Gly Asp Thr Gly Pro Ile Ile Cys Ala Gly Pro Ile His Ser

20 25 30

Asn Lys Ser Ala Asn Ile Pro His Leu Leu Gly Tyr Ser Glu Lys Ile

35 40 45

Cys Gln Ile Asp Arg Leu Ile His Val Ser Ser Trp Leu Arg Asn His

50 55 60

Ser Gln Phe Gln Gly Tyr Val Gly Gln Arg Gly Gly Arg Ser Gln Val

65 70 75 80

Ser Tyr Tyr Pro Ala Glu Asn Ser Tyr Ser Arg Trp Ser Gly Leu Leu

85 90 95

Ser Pro Cys Asp Ala Asp Trp Leu Gly Met Leu Val Val Lys Lys Ala

100 105 110

Lys Gly Ser Asp Met Ile Val Pro Gly Pro Ser Tyr Lys Gly Lys Val

115 120 125

Phe Phe Glu Arg Pro Thr Phe Asp Gly Tyr Val Gly Trp Gly Cys Gly

130 135 140

Ser Gly Lys Ser Arg Thr Glu Ser Gly Glu Leu Cys Ser Ser Asp Ser

145 150 155 160

Gly Thr Ser Ser Gly Leu Leu Pro Ser Asp Arg Val Leu Trp Ile Gly

165 170 175

Asp Val Ala Cys Gln Pro Met Thr Pro Ile Pro Glu Glu Thr Phe Leu

180 185 190

Glu Leu Lys Ser Phe Ser Gln Ser Glu Phe Pro Asp Ile Cys Lys Ile

195 200 205

Asp Gly Ile Val Phe Asn Gln Cys Glu Ser Glu Ser Leu Pro Gln Pro

210 215 220

Leu Asp Val Ala Trp Met Asp Val Gly His Ser His Lys Ile Ile Met

225 230 235 240

Arg Glu His Lys Thr Lys Trp Val Gln Glu Ser Ser Ser Lys Asp Phe

245 250 255

Val Cys Tyr Lys Glu Gly Thr Gly Pro Cys Ser Glu Ser Glu Glu Lys

260 265 270

Thr Cys Lys Thr Ser Gly Ser Cys Arg Gly Asp Met Gln Phe Cys Lys

275 280 285

Val Ala Gly Cys Glu His Gly Glu Glu Ala Ser Asp Ala Lys Cys Arg

290 295 300

Cys Ser Leu Val His Lys Pro Gly Glu Val Val Val Ser Tyr Gly Gly

305 310 315 320

Met Arg Val Arg Pro Lys Cys Tyr Gly Phe Ser Arg Met Met Ala Thr

325 330 335

Leu Glu Val Asn Pro Pro Glu Gln Arg Ile Gly Gln Cys Thr Gly Cys

340 345 350

His Leu Glu Cys Ile Asn Gly Gly Val Arg Leu Ile Thr Leu Thr Ser

355 360 365

Glu Leu Lys Ser Ala Thr Val Cys Ala Ser His Phe Cys Ser Ser Ala

370 375 380

Thr Ser Gly Lys Lys Ser Thr Glu Ile Gln Phe His Ser Gly Ser Leu

385 390 395 400

Val Gly Lys Thr Thr Ile His Val Lys Gly Ala Leu Val Asp Gly Thr

405 410 415

Glu Phe Thr Phe Glu Gly Ser Cys Met Phe Pro Asp Gly Cys Asp Ala

420 425 430

Val Asp Cys Thr Phe Cys Arg Glu Phe Leu Lys Asn Pro Gln Cys Tyr

435 440 445

Pro Ala Lys Lys Trp Leu Phe Ile Ile Ile Val Ile Leu Leu Gly Tyr

450 455 460

Ala Gly Leu Met Leu Leu Thr Asn Val Leu Lys Ala Ile Gly Val Trp

465 470 475 480

Gly Ser Trp Val Ile Ala Pro Val Lys Leu Met Phe Ala Ile Ile Lys

485 490 495

Lys Leu Met Arg Ser Val Ser Cys Leu Met Gly Lys Leu Met Asp Arg

500 505 510

Gly Arg Gln Val Ile His Glu Glu Ile Gly Glu Asn Arg Glu Gly Asn

515 520 525

Gln Asp Asp Val Arg Ile Glu Met Ala Arg Pro Arg Arg Val Arg His

530 535 540

Trp Met Tyr Ser Pro Val Ile Leu Thr Ile Leu Ala Ile Gly Leu Ala

545 550 555 560

Glu Gly Cys Asp Glu Met Val His Ala Asp Ser Lys Leu Val Ser Cys

565 570 575

Lys Gln Gly Ser Gly Asn Met Lys Glu Cys Val Thr Thr Gly Arg Ala

580 585 590

Leu Leu Pro Ala Val Asn Pro Gly Gln Glu Ala Cys Leu His Phe Thr

595 600 605

Ala Pro Gly Ser Pro Asp Ser Lys Cys Leu Lys Ile Lys Val Lys Arg

610 615 620

Ile Asn Leu Lys Cys Lys Lys Ser Ser Ser Tyr Phe Val Pro Asp Ala

625 630 635 640

Arg Ser Arg Cys Thr Ser Val Arg Arg Cys Arg Trp Ala Gly Asp Cys

645 650 655

Gln Ser Gly Cys Pro Ser His Phe Thr Ser Asn Ser Phe Ser Asp Asp

660 665 670

Trp Ala Gly Lys Met Asp Arg Ala Gly Leu Gly Phe Ser Gly Cys Ser

675 680 685

Asp Gly Cys Gly Gly Ala Ala Cys Gly Cys Phe Asn Ala Ala Pro Ser

690 695 700

Cys Ile Phe Trp Arg Lys Trp Val Glu Asn Pro His Gly Ile Ile Trp

705 710 715 720

Lys Val Ser Pro Cys Ala Ala Trp Val Pro Ser Ala Val Ile Glu Leu

725 730 735

Thr Met Pro Ser Gly Glu Val Arg Thr Phe His Pro Met Ser Gly Ile

740 745 750

Pro Thr Gln Val Phe Lys Gly Val Ser Val Thr Tyr Leu Gly Ser Asp

755 760 765

Met Glu Val Ser Gly Leu Thr Asp Leu Cys Glu Ile Glu Glu Leu Lys

770 775 780

Ser Lys Lys Leu Ala Leu Ala Pro Cys Asn Gln Ala Gly Met Gly Val

785 790 795 800

Val Gly Lys Val Gly Glu Ile Gln Cys Ser Ser Glu Glu Ser Ala Arg

805 810 815

Thr Ile Lys Lys Asp Gly Cys Ile Trp Asn Ala Asp Leu Val Gly Ile

820 825 830

Glu Leu Arg Val Asp Asp Ala Val Cys Tyr Ser Lys Ile Thr Ser Val

835 840 845

Glu Ala Val Ala Asn Tyr Ser Ala Ile Pro Thr Thr Ile Gly Gly Leu

850 855 860

Arg Phe Glu Arg Ser His Asp Ser Gln Gly Lys Ile Ser Gly Ser Pro

865 870 875 880

Leu Asp Ile Thr Ala Ile Arg Gly Ser Phe Ser Val Asn Tyr Arg Gly

885 890 895

Leu Arg Leu Ser Leu Ser Glu Val Thr Ala Thr Cys Thr Gly Glu Val

900 905 910

Thr Asn Val Ser Gly Cys Tyr Ser Cys Met Thr Gly Ala Lys Val Ser

915 920 925

Ile Lys Leu His Ser Ser Lys Asn Ser Thr Ala His Val Arg Cys Lys

930 935 940

Gly Asp Glu Thr Ala Phe Ser Val Leu Val Gly Val His Ser Tyr Thr

945 950 955 960

Val Ser Leu Ser Phe Asp His Ala Val Val Asp Glu Gln Cys Gln Leu

965 970 975

Asn Cys Gly Gly His Glu Ser Gln Val Thr Leu Lys Gly Asn Leu Ile

980 985 990

Phe Leu Asp Val Pro Lys Phe Val Asp Gly Ser Tyr Met Gln Thr Tyr

995 1000 1005

His Ser Ser Val Pro Thr Gly Ala Asn Ile Pro Ser Pro Thr Asp Trp

1010 1015 1020

Leu Asn Ala Leu Phe Gly Asn Gly Leu Ser Arg Trp Ile Leu Gly Val

1025 1030 1035 1040

Ile Gly Val Leu Leu Gly Gly Leu Ala Leu Phe Phe Leu Ile Met Ser

1045 1050 1055

Leu Phe Lys Leu Gly Thr Lys Gln Val Phe Arg Ser Arg Thr Lys Leu

1060 1065 1070

Ala ***

<210> 15

<211> 1074

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 NP

<400> 15

Met Met Lys Val Ile Trp Phe Ser Ser Leu Ile Cys Leu Val Ile Gln

1 5 10 15

Cys Ser Gly Asp Thr Gly Pro Ile Ile Cys Ala Gly Pro Ile His Ser

20 25 30

Asn Lys Ser Ala Asn Ile Pro His Leu Leu Gly Tyr Ser Glu Lys Ile

35 40 45

Cys Gln Ile Asp Arg Leu Ile His Val Ser Ser Trp Leu Arg Asn His

50 55 60

Ser Gln Phe Gln Gly Tyr Val Gly Gln Arg Gly Gly Arg Ser Gln Val

65 70 75 80

Ser Tyr Tyr Pro Ala Glu Asn Ser Tyr Ser Arg Trp Ser Gly Leu Leu

85 90 95

Ser Pro Cys Asp Ala Asp Trp Leu Gly Met Leu Val Val Lys Lys Ala

100 105 110

Lys Gly Ser Asp Met Ile Val Pro Gly Pro Ser Tyr Lys Gly Lys Val

115 120 125

Phe Phe Glu Arg Pro Thr Phe Asp Gly Tyr Val Gly Trp Gly Cys Gly

130 135 140

Ser Gly Lys Ser Arg Thr Glu Ser Gly Glu Leu Cys Ser Ser Asp Ser

145 150 155 160

Gly Thr Ser Ser Gly Leu Leu Pro Ser Asp Arg Val Leu Trp Ile Gly

165 170 175

Asp Val Ala Cys Gln Pro Met Thr Pro Ile Pro Glu Glu Thr Phe Leu

180 185 190

Glu Leu Lys Ser Phe Ser Gln Ser Glu Phe Pro Asp Ile Cys Lys Ile

195 200 205

Asp Gly Ile Val Phe Asn Gln Cys Glu Ser Glu Ser Leu Pro Gln Pro

210 215 220

Leu Asp Val Ala Trp Met Asp Val Gly His Ser His Lys Ile Ile Met

225 230 235 240

Arg Glu His Lys Thr Lys Trp Val Gln Glu Ser Ser Ser Lys Asp Phe

245 250 255

Val Cys Tyr Lys Glu Gly Thr Gly Pro Cys Ser Glu Ser Glu Glu Lys

260 265 270

Thr Cys Lys Thr Ser Gly Ser Cys Arg Gly Asp Met Gln Phe Cys Lys

275 280 285

Val Ala Gly Cys Glu His Gly Glu Glu Ala Ser Asp Ala Lys Cys Arg

290 295 300

Cys Ser Leu Val His Lys Pro Gly Glu Val Val Val Ser Tyr Gly Gly

305 310 315 320

Met Arg Val Arg Pro Lys Cys Tyr Gly Phe Ser Arg Met Met Ala Thr

325 330 335

Leu Glu Val Asn Pro Pro Glu Gln Arg Ile Gly Gln Cys Thr Gly Cys

340 345 350

His Leu Glu Cys Ile Asn Gly Gly Val Arg Leu Ile Thr Leu Thr Ser

355 360 365

Glu Leu Lys Ser Ala Thr Val Cys Ala Ser His Phe Cys Ser Ser Ala

370 375 380

Thr Ser Gly Lys Lys Ser Thr Glu Ile Gln Phe His Ser Gly Ser Leu

385 390 395 400

Val Gly Lys Thr Thr Ile His Val Lys Gly Ala Leu Val Asp Gly Thr

405 410 415

Glu Phe Thr Phe Glu Gly Ser Cys Met Phe Pro Asp Gly Cys Asp Ala

420 425 430

Val Asp Cys Thr Phe Cys Arg Glu Phe Leu Lys Asn Pro Gln Cys Tyr

435 440 445

Pro Ala Lys Lys Trp Leu Phe Ile Ile Ile Val Ile Leu Leu Gly Tyr

450 455 460

Ala Gly Leu Met Leu Leu Thr Asn Val Leu Lys Ala Ile Gly Val Trp

465 470 475 480

Gly Ser Trp Val Ile Ala Pro Val Lys Leu Met Phe Ala Ile Ile Lys

485 490 495

Lys Leu Met Arg Ser Val Ser Cys Leu Met Gly Lys Leu Met Asp Arg

500 505 510

Gly Arg Gln Val Ile His Glu Glu Ile Gly Glu Asn Arg Glu Gly Asn

515 520 525

Gln Asp Asp Val Arg Ile Glu Met Ala Arg Pro Arg Arg Val Arg His

530 535 540

Trp Met Tyr Ser Pro Val Ile Leu Thr Ile Leu Ala Ile Gly Leu Ala

545 550 555 560

Glu Gly Cys Asp Glu Met Val His Ala Asp Ser Lys Leu Val Ser Cys

565 570 575

Lys Gln Gly Ser Gly Asn Met Lys Glu Cys Val Thr Thr Gly Arg Ala

580 585 590

Leu Leu Pro Ala Val Asn Pro Gly Gln Glu Ala Cys Leu His Phe Thr

595 600 605

Ala Pro Gly Ser Pro Asp Ser Lys Cys Leu Lys Ile Lys Val Lys Arg

610 615 620

Ile Asn Leu Lys Cys Lys Lys Ser Ser Ser Tyr Phe Val Pro Asp Ala

625 630 635 640

Arg Ser Arg Cys Thr Ser Val Arg Arg Cys Arg Trp Ala Gly Asp Cys

645 650 655

Gln Ser Gly Cys Pro Ser His Phe Thr Ser Asn Ser Phe Ser Asp Asp

660 665 670

Trp Ala Gly Lys Met Asp Arg Ala Gly Leu Gly Phe Ser Gly Cys Ser

675 680 685

Asp Gly Cys Gly Gly Ala Ala Cys Gly Cys Phe Asn Ala Ala Pro Ser

690 695 700

Cys Ile Phe Trp Arg Lys Trp Val Glu Asn Pro His Gly Ile Ile Trp

705 710 715 720

Lys Val Ser Pro Cys Ala Ala Trp Val Pro Ser Ala Val Ile Glu Leu

725 730 735

Thr Met Pro Ser Gly Glu Val Arg Thr Phe His Pro Met Ser Gly Ile

740 745 750

Pro Thr Gln Val Phe Lys Gly Val Ser Val Thr Tyr Leu Gly Ser Asp

755 760 765

Met Glu Val Ser Gly Leu Thr Asp Leu Cys Glu Ile Glu Glu Leu Lys

770 775 780

Ser Lys Lys Leu Ala Leu Ala Pro Cys Asn Gln Ala Gly Met Gly Val

785 790 795 800

Val Gly Lys Val Gly Glu Ile Gln Cys Ser Ser Glu Glu Ser Ala Arg

805 810 815

Thr Ile Lys Lys Asp Gly Cys Ile Trp Asn Ala Asp Leu Val Gly Ile

820 825 830

Glu Leu Arg Val Asp Asp Ala Val Cys Tyr Ser Lys Ile Thr Ser Val

835 840 845

Glu Ala Val Ala Asn Tyr Ser Ala Ile Pro Thr Thr Ile Gly Gly Leu

850 855 860

Arg Phe Glu Arg Ser His Asp Ser Gln Gly Lys Ile Ser Gly Ser Pro

865 870 875 880

Leu Asp Ile Thr Ala Ile Arg Gly Ser Phe Ser Val Asn Tyr Arg Gly

885 890 895

Leu Arg Leu Ser Leu Ser Glu Val Thr Ala Thr Cys Thr Gly Glu Val

900 905 910

Thr Asn Val Ser Gly Cys Tyr Ser Cys Met Thr Gly Ala Lys Val Ser

915 920 925

Ile Lys Leu His Ser Ser Lys Asn Ser Thr Ala His Val Arg Cys Lys

930 935 940

Gly Asp Glu Thr Ala Phe Ser Val Leu Val Gly Val His Ser Tyr Thr

945 950 955 960

Val Ser Leu Ser Phe Asp His Ala Val Val Asp Glu Gln Cys Gln Leu

965 970 975

Asn Cys Gly Gly His Glu Ser Gln Val Thr Leu Lys Gly Asn Leu Ile

980 985 990

Phe Leu Asp Val Pro Lys Phe Val Asp Gly Ser Tyr Met Gln Thr Tyr

995 1000 1005

His Ser Ser Val Pro Thr Gly Ala Asn Ile Pro Ser Pro Thr Asp Trp

1010 1015 1020

Leu Asn Ala Leu Phe Gly Asn Gly Leu Ser Arg Trp Ile Leu Gly Val

1025 1030 1035 1040

Ile Gly Val Leu Leu Gly Gly Leu Ala Leu Phe Phe Leu Ile Met Ser

1045 1050 1055

Leu Phe Lys Leu Gly Thr Lys Gln Val Phe Arg Ser Arg Thr Lys Leu

1060 1065 1070

Ala ***

<210> 16

<211> 294

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-1 NS

<400> 16

Met Ser Leu Ser Lys Cys Ser Asn Val Asp Leu Lys Ser Val Ala Met

1 5 10 15

Asn Ala Asn Thr Val Arg Leu Glu Pro Ser Leu Gly Glu Tyr Pro Thr

20 25 30

Leu Arg Arg Asp Leu Val Glu Cys Ser Cys Ser Val Leu Thr Leu Ser

35 40 45

Met Val Lys Arg Met Gly Lys Met Thr Asn Thr Val Trp Leu Phe Gly

50 55 60

Asn Pro Lys Asn Pro Leu His Gln Leu Glu Pro Gly Leu Glu Gln Leu

65 70 75 80

Leu Asp Met Tyr Tyr Lys Asp Met Arg Cys Tyr Ser Gln Arg Glu Leu

85 90 95

Ser Ala Leu Arg Trp Pro Ser Gly Lys Pro Ser Val Trp Phe Leu Gln

100 105 110

Ala Ala His Met Phe Phe Ser Ile Lys Asn Ser Trp Ala Met Glu Thr

115 120 125

Gly Arg Glu Asn Trp Arg Gly Leu Phe His Arg Ile Thr Lys Gly Lys

130 135 140

Lys Tyr Leu Phe Glu Gly Asp Met Ile Leu Asp Ser Leu Glu Ala Ile

145 150 155 160

Glu Lys Arg Arg Leu Arg Leu Gly Leu Pro Glu Ile Leu Ile Thr Gly

165 170 175

Leu Ser Pro Ile Leu Asp Val Ala Leu Leu Gln Ile Glu Ser Leu Ala

180 185 190

Arg Leu Arg Gly Met Ser Leu Asn His His Leu Phe Thr Ser Ser Ser

195 200 205

Leu Arg Lys Pro Leu Leu Asp Cys Trp Asp Phe Phe Ile Pro Ile Arg

210 215 220

Lys Lys Arg Thr Asp Gly Ser Tyr Ser Ile Leu Asp Glu Asp Asp Glu

225 230 235 240

Leu Gly Val Leu Gln Gly Tyr Pro Tyr Leu Met Ala His Tyr Leu Asn

245 250 255

Arg Cys Pro Phe His Asn Leu Ile Arg Phe Asp Glu Glu Leu Arg Thr

260 265 270

Ala Ala Leu Asn Thr Ile Trp Gly Arg Asp Trp Pro Ala Ile Gly Asp

275 280 285

Leu Pro Lys Glu Val ***

290

<210> 17

<211> 2085

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 L

<400> 17

Met Asn Leu Glu Val Leu Cys Gly Arg Ile Asn Val Glu Asn Gly Leu

1 5 10 15

Ser Leu Gly Glu Pro Gly Leu Tyr Asp Gln Ile Tyr Asp Arg Pro Gly

20 25 30

Leu Pro Asp Leu Asp Val Thr Val Asp Ala Thr Gly Val Thr Val Asp

35 40 45

Ile Gly Ala Val Pro Asp Ser Ala Ser Gln Leu Gly Ser Ser Ile Asn

50 55 60

Ala Gly Leu Ile Thr Ile Gln Leu Ser Glu Ala Tyr Lys Ile Asn His

65 70 75 80

Asp Phe Thr Phe Ser Gly Leu Ser Lys Thr Thr Asp Arg Arg Leu Ser

85 90 95

Glu Val Phe Pro Ile Thr His Asp Gly Ser Asp Gly Met Thr Pro Asp

100 105 110

Val Ile His Thr Arg Leu Asp Gly Thr Ile Val Val Val Glu Phe Ser

115 120 125

Thr Thr Arg Ser His Asn Ile Gly Gly Leu Glu Thr Ala Tyr Arg Thr

130 135 140

Lys Ile Glu Lys Tyr Arg Asp Pro Ile Ser Arg Arg Val Asp Ile Met

145 150 155 160

Glu Asn Pro Arg Val Phe Phe Gly Val Ile Val Val Ser Ser Gly Gly

165 170 175

Val Leu Ser Asn Met Pro Leu Thr Gln Asp Glu Ala Glu Glu Leu Met

180 185 190

Tyr Arg Phe Cys Ile Ala Asn Glu Ile Tyr Thr Lys Ala Arg Ser Met

195 200 205

Asp Ala Asp Ile Glu Leu Gln Lys Ser Glu Glu Glu Leu Glu Ala Ile

210 215 220

Ser Arg Ala Leu Ser Phe Phe Ser Leu Phe Glu Pro Asn Ile Glu Lys

225 230 235 240

Val Glu Gly Thr Phe Pro Asn Ser Glu Ile Glu Met Leu Glu Gln Phe

245 250 255

Leu Ser Thr Pro Ala Asp Val Asp Phe Ile Thr Lys Thr Leu Lys Ala

260 265 270

Lys Glu Val Glu Ala Tyr Ala Asp Leu Cys Asp Ser His Tyr Leu Lys

275 280 285

Pro Glu Lys Thr Ile Gln Glu Arg Leu Glu Ile Asn Arg Cys Glu Ala

290 295 300

Ile Asp Lys Thr Gln Asp Leu Leu Ala Ser Leu His Ala Arg Ser Asn

305 310 315 320

Lys Gln Thr Ser Leu Asn Arg Gly Thr Val Lys Leu Pro Pro Trp Leu

325 330 335

Pro Lys Pro Ser Ser Glu Ser Ile Asp Ile Lys Thr Asp Ser Gly Phe

340 345 350

Gly Ser Leu Met Asp His Gly Ala Tyr Gly Glu Leu Trp Ala Lys Cys

355 360 365

Leu Leu Asp Val Ser Leu Gly Asn Val Glu Gly Val Ile Ser Asp Pro

370 375 380

Ala Lys Glu Leu Asp Ile Ala Ile Ser Asp Asp Pro Glu Lys Asp Thr

385 390 395 400

Pro Lys Glu Ala Lys Ile Thr Tyr Arg Arg Phe Lys Pro Ala Leu Ser

405 410 415

Ser Ser Ala Arg Gln Glu Phe Ser Leu Gln Gly Val Glu Gly Lys Lys

420 425 430

Trp Lys Arg Met Ala Ala Asn Gln Lys Lys Glu Lys Glu Ser His Glu

435 440 445

Ala Leu Ser Pro Phe Leu Asp Val Glu Asp Ile Gly Asp Phe Leu Thr

450 455 460

Phe Asn Asn Leu Leu Ala Asp Ser Arg Tyr Gly Asp Glu Ser Val Gln

465 470 475 480

Arg Ala Val Ser Ile Leu Leu Glu Lys Ala Ser Ala Met Gln Asn Thr

485 490 495

Glu Leu Thr His Ala Leu Asn Asp Ser Phe Lys Arg Asn Leu Ser Ser

500 505 510

Asn Val Val Gln Trp Ser Leu Trp Val Ser Cys Leu Ala Gln Glu Leu

515 520 525

Ala Ser Ala Leu Lys Gln His Cys Arg Ala Gly Glu Phe Ile Ile Lys

530 535 540

Lys Leu Lys Phe Trp Pro Ile Tyr Val Ile Ile Lys Pro Thr Lys Ser

545 550 555 560

Ser Ser His Ile Phe Tyr Ser Leu Gly Ile Arg Lys Ala Asp Val Thr

565 570 575

Arg Arg Leu Thr Gly Arg Val Phe Ser Asp Thr Ile Asp Ala Gly Glu

580 585 590

Trp Glu Leu Thr Glu Phe Lys Ser Leu Lys Thr Cys Lys Leu Thr Asn

595 600 605

Leu Val Asn Leu Pro Cys Thr Met Leu Asn Ser Ile Ala Phe Trp Arg

610 615 620

Glu Lys Leu Gly Val Ala Pro Trp Leu Val Arg Lys Pro Cys Ser Glu

625 630 635 640

Leu Arg Glu Gln Val Gly Leu Thr Phe Leu Ile Ser Leu Glu Asp Lys

645 650 655

Ser Lys Thr Glu Glu Ile Ile Thr Leu Thr Arg Tyr Thr Gln Met Glu

660 665 670

Gly Phe Val Ser Pro Pro Met Leu Pro Lys Pro Gln Lys Met Leu Gly

675 680 685

Lys Leu Asp Gly Pro Leu Arg Thr Lys Leu Gln Val Tyr Leu Leu Arg

690 695 700

Lys His Leu Asp Cys Met Val Arg Ile Ala Ser Gln Pro Phe Ser Leu

705 710 715 720

Ile Pro Arg Glu Gly Arg Val Glu Trp Gly Gly Thr Phe His Ala Ile

725 730 735

Ser Gly Arg Ser Thr Asn Leu Glu Asn Met Val Asn Ser Trp Tyr Ile

740 745 750

Gly Tyr Tyr Lys Asn Lys Glu Glu Ser Thr Glu Leu Asn Ala Leu Gly

755 760 765

Glu Met Tyr Lys Lys Ile Val Glu Met Glu Glu Asp Lys Pro Ser Ser

770 775 780

Pro Glu Phe Leu Gly Trp Gly Asp Thr Asp Ser Pro Lys Lys His Glu

785 790 795 800

Phe Ser Arg Ser Phe Leu Arg Ala Ala Cys Ser Ser Leu Glu Arg Glu

805 810 815

Ile Ala Gln Arg His Gly Arg Gln Trp Lys Gln Asn Leu Glu Glu Arg

820 825 830

Val Leu Arg Glu Ile Gly Thr Lys Asn Ile Leu Asp Leu Ala Ser Met

835 840 845

Lys Ala Thr Ser Asn Phe Ser Lys Asp Trp Glu Leu Tyr Ser Glu Val

850 855 860

Gln Thr Lys Glu Tyr His Arg Ser Lys Leu Leu Glu Lys Met Ala Thr

865 870 875 880

Leu Ile Glu Lys Gly Val Met Trp Tyr Ile Asp Ala Val Gly Gln Ala

885 890 895

Trp Lys Ala Val Leu Asp Asp Gly Cys Met Arg Ile Cys Leu Phe Lys

900 905 910

Lys Asn Gln His Gly Gly Leu Arg Glu Ile Tyr Val Met Asp Ala Asn

915 920 925

Ala Arg Leu Val Gln Phe Gly Val Glu Thr Met Ala Arg Cys Val Cys

930 935 940

Glu Leu Ser Pro His Glu Thr Val Ala Asn Pro Arg Leu Lys Asn Ser

945 950 955 960

Ile Ile Glu Asn His Gly Leu Lys Ser Ala Arg Ser Leu Gly Pro Gly

965 970 975

Ser Ile Asn Ile Asn Ser Ser Asn Asp Ala Lys Lys Trp Asn Gln Gly

980 985 990

His Tyr Thr Thr Lys Leu Ala Leu Val Leu Cys Trp Phe Met Pro Ala

995 1000 1005

Lys Phe His Arg Phe Ile Trp Ala Ala Ile Ser Met Phe Arg Arg Lys

1010 1015 1020

Lys Met Met Val Asp Leu Arg Phe Leu Ala His Leu Ser Ser Lys Ser

1025 1030 1035 1040

Glu Ser Arg Ser Ser Asp Pro Phe Arg Glu Ala Met Thr Asp Ala Phe

1045 1050 1055

His Gly Asn Arg Glu Val Ser Trp Met Asp Lys Gly Arg Thr Tyr Ile

1060 1065 1070

Lys Thr Glu Thr Gly Met Met Gln Gly Ile Leu His Phe Thr Ser Ser

1075 1080 1085

Leu Leu His Ser Cys Val Gln Ser Phe Tyr Lys Ser Tyr Phe Val Ser

1090 1095 1100

Lys Leu Lys Glu Gly Tyr Met Gly Glu Ser Ile Asn Gly Val Val Asp

1105 1110 1115 1120

Val Ile Glu Gly Ser Asp Asp Ser Ala Ile Met Ile Ser Ile Arg Pro

1125 1130 1135

Lys Ser Asp Met Asp Glu Val Arg Ser Arg Phe Phe Val Ala Asn Leu

1140 1145 1150

Leu His Ser Val Lys Phe Leu Asn Pro Leu Phe Gly Ile Tyr Ser Ser

1155 1160 1165

Glu Lys Ser Thr Val Asn Thr Val Tyr Cys Val Glu Tyr Asn Ser Glu

1170 1175 1180

Phe His Phe His Arg His Leu Val Arg Pro Thr Leu Arg Trp Ile Ala

1185 1190 1195 1200

Ala Ser His Gln Ile Ser Glu Thr Glu Ala Leu Ala Ser Arg Gln Glu

1205 1210 1215

Asp Tyr Ser Asn Leu Leu Thr Gln Cys Leu Glu Gly Gly Ala Ser Phe

1220 1225 1230

Ser Leu Thr Tyr Leu Ile Gln Cys Ala Gln Leu Leu His His Tyr Met

1235 1240 1245

Leu Leu Gly Leu Cys Leu His Pro Leu Phe Gly Thr Phe Met Gly Met

1250 1255 1260

Leu Ile Ser Asp Pro Asp Pro Ala Leu Gly Phe Phe Leu Met Asp Asn

1265 1270 1275 1280

Pro Ala Phe Ala Gly Gly Ala Gly Phe Arg Phe Asn Leu Trp Arg Ala

1285 1290 1295

Cys Lys Thr Thr Asp Leu Gly Arg Lys Tyr Ala Tyr Tyr Phe Asn Glu

1300 1305 1310

Ile Gln Gly Lys Thr Lys Gly Asp Glu Asp Tyr Arg Ala Leu Asp Ala

1315 1320 1325

Thr Ser Gly Gly Thr Leu Ser His Ser Val Met Val Tyr Trp Gly Asp

1330 1335 1340

Arg Lys Lys Tyr Gln Ala Leu Leu Asn Arg Met Gly Leu Pro Glu Asp

1345 1350 1355 1360

Trp Val Glu Gln Ile Asp Glu Asn Pro Gly Val Leu Tyr Arg Arg Ala

1365 1370 1375

Ala Asn Lys Lys Glu Leu Leu Leu Lys Leu Ala Glu Lys Val His Ser

1380 1385 1390

Pro Gly Val Thr Ser Ser Leu Ser Lys Gly His Val Val Pro Arg Val

1395 1400 1405

Val Ala Ala Gly Val Tyr Leu Leu Ser Arg His Cys Phe Arg Phe Ser

1410 1415 1420

Ser Ser Ile His Gly Arg Gly Ser Ala Gln Lys Ala Ser Leu Ile Lys

1425 1430 1435 1440

Leu Leu Met Met Ser Ser Ile Ser Ala Met Lys His Gly Gly Ser Leu

1445 1450 1455

Asn Pro Asn Gln Glu Arg Met Leu Phe Pro Gln Ala Gln Glu Tyr Asp

1460 1465 1470

Arg Val Cys Thr Leu Leu Glu Glu Val Glu His Leu Thr Gly Lys Phe

1475 1480 1485

Val Val Arg Glu Arg Asn Ile Val Arg Ser Arg Ile Asp Leu Phe Gln

1490 1495 1500

Glu Pro Val Asp Leu Arg Cys Lys Ala Glu Asp Leu Val Ser Glu Val

1505 1510 1515 1520

Trp Phe Gly Leu Lys Arg Thr Lys Leu Gly Pro Arg Leu Leu Lys Glu

1525 1530 1535

Glu Trp Asp Lys Leu Arg Ala Ser Phe Ala Trp Leu Ser Thr Asp Pro

1540 1545 1550

Ser Glu Thr Leu Arg Asp Gly Pro Phe Leu Ser His Val Gln Phe Arg

1555 1560 1565

Asn Phe Ile Ala His Val Asp Ala Lys Ser Arg Ser Val Arg Leu Leu

1570 1575 1580

Gly Ala Pro Val Lys Lys Ser Gly Gly Val Thr Thr Ile Ser Gln Val

1585 1590 1595 1600

Val Arg Met Asn Phe Phe Pro Gly Phe Ser Leu Glu Ala Glu Lys Ser

1605 1610 1615

Leu Asp Asn Gln Glu Arg Leu Glu Ser Ile Ser Ile Leu Lys His Val

1620 1625 1630

Leu Phe Met Val Leu Asn Gly Pro Tyr Thr Glu Glu Tyr Lys Leu Glu

1635 1640 1645

Met Ile Ile Glu Ala Phe Ser Thr Leu Val Ile Pro Gln Pro Ser Glu

1650 1655 1660

Val Ile Arg Lys Ser Arg Thr Met Thr Leu Cys Leu Leu Ser Asn Tyr

1665 1670 1675 1680

Leu Ser Ser Arg Gly Gly Ser Ile Leu Asp Gln Ile Glu Arg Ala Gln

1685 1690 1695

Ser Gly Thr Leu Gly Gly Phe Ser Lys Pro Gln Lys Thr Phe Ile Arg

1700 1705 1710

Pro Gly Gly Gly Ile Gly Tyr Lys Gly Lys Gly Val Trp Thr Gly Val

1715 1720 1725

Met Glu Asp Thr His Val Gln Ile Leu Ile Asp Gly Asp Gly Thr Ser

1730 1735 1740

Asn Trp Leu Glu Glu Ile Arg Leu Ser Ser Asp Ala Arg Leu Tyr Asp

1745 1750 1755 1760

Val Ile Glu Ser Ile Arg Arg Leu Cys Asp Asp Leu Gly Ile Asn Asn

1765 1770 1775

Arg Val Ala Ser Ala Tyr Arg Gly His Cys Met Val Arg Leu Ser Gly

1780 1785 1790

Phe Lys Ile Lys Pro Ala Ser Arg Thr Asp Gly Cys Pro Val Arg Ile

1795 1800 1805

Met Glu Arg Gly Phe Arg Ile Arg Glu Leu Gln Asn Pro Asp Glu Val

1810 1815 1820

Lys Met Arg Val Arg Gly Asp Ile Leu Asn Leu Ser Val Thr Ile Gln

1825 1830 1835 1840

Glu Gly Arg Val Met Asn Ile Leu Ser Tyr Arg Pro Arg Asp Thr Asp

1845 1850 1855

Ile Ser Glu Ser Ala Ala Ala Tyr Leu Trp Ser Asn Arg Asp Leu Phe

1860 1865 1870

Ser Phe Gly Lys Lys Glu Pro Ser Cys Ser Trp Ile Cys Leu Lys Thr

1875 1880 1885

Leu Asp Asn Trp Ala Trp Ser His Ala Ser Val Leu Leu Ala Asn Asp

1890 1895 1900

Arg Lys Thr Gln Gly Ile Asp Asn Arg Ala Met Gly Asn Ile Phe Arg

1905 1910 1915 1920

Asp Cys Leu Glu Gly Ser Leu Arg Lys Gln Gly Leu Met Arg Ser Lys

1925 1930 1935

Leu Thr Glu Met Val Glu Lys Asn Val Val Pro Leu Thr Thr Gln Glu

1940 1945 1950

Leu Val Asp Ile Leu Glu Glu Asp Ile Asp Phe Ser Asp Val Ile Ala

1955 1960 1965

Val Glu Leu Ser Glu Gly Ser Leu Asp Ile Glu Ser Ile Phe Asp Gly

1970 1975 1980

Ala Pro Ile Leu Trp Ser Ala Glu Val Glu Glu Phe Gly Glu Gly Val

1985 1990 1995 2000

Val Ala Val Ser Tyr Ser Ser Lys Tyr Tyr His Leu Thr Leu Met Asp

2005 2010 2015

Gln Ala Ala Ile Thr Met Cys Ala Ile Met Gly Lys Glu Gly Cys Arg

2020 2025 2030

Gly Leu Leu Thr Glu Lys Arg Cys Met Ala Ala Ile Arg Glu Gln Val

2035 2040 2045

Arg Pro Phe Leu Ile Phe Leu Gln Ile Pro Glu Asp Ser Ile Ser Trp

2050 2055 2060

Val Ser Asp Gln Phe Cys Asp Ser Arg Gly Leu Asp Glu Glu Ser Thr

2065 2070 2075 2080

Ile Met Trp Gly ***

2085

<210> 18

<211> 1074

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 M

<400> 18

Met Met Lys Val Ile Trp Phe Ser Ser Leu Ile Cys Leu Val Ile Gln

1 5 10 15

Cys Ser Gly Asp Thr Gly Pro Ile Ile Cys Ala Gly Pro Ile His Ser

20 25 30

Asn Lys Ser Ala Asp Ile Pro His Leu Leu Gly Tyr Ser Glu Lys Ile

35 40 45

Cys Gln Ile Asp Arg Leu Ile His Val Ser Ser Trp Leu Arg Asn His

50 55 60

Ser Gln Phe Gln Gly Tyr Val Gly Gln Arg Gly Gly Arg Ser Gln Val

65 70 75 80

Ser Tyr Phe Pro Ala Glu Asn Ser Tyr Ser Arg Trp Ser Gly Leu Leu

85 90 95

Ser Pro Cys Asp Ala Asp Trp Leu Gly Met Leu Val Val Lys Lys Ala

100 105 110

Lys Gly Ser Asp Met Ile Val Pro Gly Pro Ser Tyr Lys Gly Lys Val

115 120 125

Phe Phe Glu Arg Pro Thr Phe Asp Gly Tyr Val Gly Trp Gly Cys Gly

130 135 140

Ser Gly Lys Ser Arg Thr Glu Ser Gly Glu Leu Cys Ser Ser Asp Ser

145 150 155 160

Gly Thr Ser Ser Gly Leu Leu Pro Ser Asn Arg Val Leu Trp Ile Gly

165 170 175

Asp Val Ala Cys Gln Pro Met Thr Pro Ile Pro Glu Glu Thr Phe Leu

180 185 190

Glu Leu Lys Ser Phe Ser Gln Ser Glu Phe Pro Asp Ile Cys Lys Ile

195 200 205

Asp Gly Ile Val Phe Asn Gln Cys Glu Ser Glu Ser Leu Pro Gln Pro

210 215 220

Phe Asp Val Ala Trp Met Asp Val Gly His Ser His Lys Ile Ile Met

225 230 235 240

Arg Glu His Lys Thr Lys Trp Val Gln Glu Ser Ser Ser Lys Asp Phe

245 250 255

Val Cys Tyr Lys Glu Gly Thr Gly Pro Cys Ser Glu Ser Glu Glu Lys

260 265 270

Thr Cys Lys Thr Ser Gly Ser Cys Arg Gly Asp Met Gln Phe Cys Lys

275 280 285

Val Ala Gly Cys Glu His Gly Glu Glu Thr Ser Glu Ala Lys Cys Arg

290 295 300

Cys Ser Leu Val His Lys Pro Gly Glu Val Val Val Ser Tyr Gly Gly

305 310 315 320

Met Arg Val Arg Pro Lys Cys Tyr Gly Phe Ser Arg Met Met Ala Thr

325 330 335

Leu Glu Val Asn Pro Pro Glu Gln Arg Ile Gly Gln Cys Thr Gly Cys

340 345 350

His Leu Glu Cys Ile Asn Gly Gly Val Arg Ile Ile Thr Leu Thr Ser

355 360 365

Glu Leu Lys Ser Ala Thr Val Cys Ala Ser His Phe Cys Ser Ser Ala

370 375 380

Thr Ser Gly Lys Lys Ser Thr Glu Ile Gln Phe His Ser Gly Ser Leu

385 390 395 400

Val Gly Lys Thr Ala Ile His Val Lys Gly Ala Leu Val Asp Gly Thr

405 410 415

Glu Phe Thr Phe Glu Gly Ser Cys Met Phe Pro Asp Gly Cys Asp Ala

420 425 430

Val Asp Cys Thr Phe Cys Arg Glu Phe Leu Lys Asn Pro Gln Cys Tyr

435 440 445

Pro Ala Lys Lys Trp Leu Phe Ile Ile Ile Val Ile Leu Leu Gly Tyr

450 455 460

Ala Gly Leu Met Leu Leu Thr Asn Val Leu Lys Ala Ile Gly Val Trp

465 470 475 480

Gly Ser Trp Val Ile Ala Pro Val Lys Leu Met Phe Ala Ile Ile Lys

485 490 495

Lys Leu Met Arg Ser Val Ser Cys Leu Met Gly Lys Leu Met Asp Arg

500 505 510

Gly Arg Gln Val Ile His Glu Glu Ile Gly Glu Asn Arg Glu Gly Asn

515 520 525

Gln Asp Asp Val Arg Ile Glu Met Ala Arg Pro Arg Arg Val Arg His

530 535 540

Trp Met Tyr Ser Pro Val Ile Leu Thr Ile Leu Ala Ile Gly Leu Ala

545 550 555 560

Glu Gly Cys Asp Glu Met Val His Ala Asp Ser Lys Leu Val Ser Cys

565 570 575

Lys Gln Gly Ser Gly Asn Met Lys Glu Cys Val Thr Thr Gly Arg Ala

580 585 590

Leu Leu Pro Ala Val Asn Pro Gly Gln Glu Ala Cys Leu His Phe Thr

595 600 605

Ala Pro Gly Ser Pro Asp Ser Lys Cys Leu Lys Ile Lys Val Lys Arg

610 615 620

Ile Asn Leu Lys Cys Lys Lys Ser Ser Ser Tyr Phe Val Pro Asp Ala

625 630 635 640

Arg Ser Arg Cys Thr Ser Val Arg Arg Cys Arg Trp Ala Gly Asp Cys

645 650 655

Gln Ser Gly Cys Pro Ser His Phe Thr Ser Asn Ser Phe Ser Asp Asp

660 665 670

Trp Ala Gly Lys Met Asp Arg Ala Gly Leu Gly Phe Ser Gly Cys Ser

675 680 685

Asp Gly Cys Gly Gly Ala Ala Cys Gly Cys Phe Asn Ala Ala Pro Ser

690 695 700

Cys Ile Phe Trp Arg Lys Trp Val Glu Asn Pro His Gly Ile Ile Trp

705 710 715 720

Lys Val Ser Pro Cys Ala Ala Trp Val Pro Ser Ala Val Ile Glu Leu

725 730 735

Thr Met Pro Ser Gly Glu Val Arg Thr Phe His Pro Met Ser Gly Ile

740 745 750

Pro Thr Gln Val Phe Lys Gly Val Ser Val Thr Tyr Leu Gly Ser Asp

755 760 765

Met Glu Val Ser Gly Leu Thr Asp Leu Cys Glu Ile Glu Glu Leu Lys

770 775 780

Ser Lys Lys Leu Ala Leu Ala Pro Cys Asn Gln Ala Gly Met Gly Val

785 790 795 800

Val Gly Lys Val Gly Glu Ile Gln Cys Ser Ser Glu Glu Ser Ala Arg

805 810 815

Thr Ile Lys Lys Asp Gly Cys Ile Trp Asn Ala Asp Leu Val Gly Ile

820 825 830

Glu Leu Arg Val Asp Asp Ala Val Cys Tyr Ser Lys Ile Thr Ser Val

835 840 845

Glu Ala Val Ala Asn Tyr Ser Ala Ile Pro Thr Thr Ile Gly Gly Leu

850 855 860

Arg Phe Glu Arg Ser His Asp Ser Gln Gly Lys Ile Ser Gly Ser Pro

865 870 875 880

Leu Asp Ile Thr Ala Ile Arg Gly Ser Phe Ser Val Asn Tyr Arg Gly

885 890 895

Leu Arg Leu Ser Leu Ser Glu Ile Thr Ala Thr Cys Thr Gly Glu Val

900 905 910

Thr Asn Val Ser Gly Cys Tyr Ser Cys Met Thr Gly Ala Lys Val Ser

915 920 925

Ile Lys Leu His Ser Ser Lys Asn Ser Thr Ala His Val Arg Cys Lys

930 935 940

Gly Asp Glu Thr Ala Phe Ser Val Leu Glu Gly Val His Ser Tyr Thr

945 950 955 960

Val Ser Leu Ser Phe Asp His Ala Val Val Asp Glu Gln Cys Gln Leu

965 970 975

Asn Cys Gly Gly His Glu Ser Gln Val Thr Leu Lys Gly Asn Leu Ile

980 985 990

Phe Leu Asp Val Pro Lys Phe Val Asp Gly Ser Tyr Met Gln Thr Tyr

995 1000 1005

His Ser Ser Val Pro Thr Gly Ala Asn Ile Pro Ser Pro Thr Asp Trp

1010 1015 1020

Leu Asn Ala Leu Phe Gly Asn Gly Leu Ser Arg Trp Ile Leu Gly Val

1025 1030 1035 1040

Ile Gly Val Leu Leu Gly Gly Leu Ala Leu Phe Phe Leu Ile Met Ser

1045 1050 1055

Leu Phe Lys Leu Gly Thr Lys Gln Val Phe Arg Ser Arg Thr Lys Leu

1060 1065 1070

Ala ***

<210> 19

<211> 246

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 NP

<400> 19

Met Ser Glu Trp Ser Arg Ile Ala Val Glu Phe Gly Glu Gln Gln Leu

1 5 10 15

Asn Leu Thr Glu Leu Glu Asp Phe Ala Arg Glu Leu Ala Tyr Glu Gly

20 25 30

Leu Asp Pro Ala Leu Ile Ile Lys Lys Leu Lys Glu Thr Gly Gly Asp

35 40 45

Asp Trp Val Arg Asp Thr Lys Phe Ile Ile Val Phe Ala Leu Thr Arg

50 55 60

Gly Asn Lys Ile Val Lys Ala Ser Gly Lys Met Ser Asn Ser Gly Ser

65 70 75 80

Lys Arg Leu Met Ala Leu Gln Glu Lys Tyr Gly Leu Val Glu Arg Ala

85 90 95

Glu Thr Arg Leu Ser Ile Thr Pro Val Arg Val Ala Gln Ser Leu Pro

100 105 110

Thr Trp Thr Cys Ala Ala Ala Ala Ala Leu Lys Glu Tyr Leu Pro Val

115 120 125

Gly Pro Ala Val Met Asn Leu Lys Val Glu Asn Tyr Pro Pro Glu Met

130 135 140

Met Cys Met Ala Phe Gly Ser Leu Ile Pro Thr Ala Gly Val Ser Glu

145 150 155 160

Ala Thr Thr Lys Thr Leu Met Glu Ala Tyr Ser Leu Trp Gln Asp Ala

165 170 175

Phe Thr Lys Thr Ile Asn Val Lys Met Arg Gly Ala Ser Lys Thr Glu

180 185 190

Val Tyr Asn Ser Phe Arg Asp Pro Leu His Ala Ala Val Asn Ser Val

195 200 205

Phe Phe Pro Asn Asp Val Arg Val Lys Trp Leu Lys Ala Lys Gly Ile

210 215 220

Leu Gly Pro Asp Gly Val Pro Ser Arg Ala Ala Glu Val Ala Ala Ala

225 230 235 240

Ala Tyr Arg Asn Leu ***

245

<210> 20

<211> 294

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-2 NS

<400> 20

Met Ser Leu Ser Lys Cys Ser Asn Val Asp Leu Lys Ser Val Ala Met

1 5 10 15

Asn Ala Asn Thr Val Arg Leu Glu Pro Ser Leu Gly Glu Tyr Pro Thr

20 25 30

Leu Arg Arg Asp Leu Val Glu Cys Ser Cys Ser Val Leu Thr Leu Ser

35 40 45

Met Val Lys Arg Met Gly Lys Met Thr Asn Thr Val Trp Leu Phe Gly

50 55 60

Asn Pro Lys Asn Pro Leu His Gln Leu Glu Pro Gly Leu Glu Gln Leu

65 70 75 80

Leu Asp Met Tyr Tyr Lys Asp Met Arg Cys Tyr Ser Gln Arg Glu Leu

85 90 95

Ser Ala Leu Arg Trp Pro Ser Gly Lys Pro Ser Val Trp Phe Leu Gln

100 105 110

Ala Ala His Met Phe Phe Ser Ile Lys Asn Ser Trp Ala Met Glu Thr

115 120 125

Gly Arg Glu Asn Trp Arg Gly Leu Phe His Arg Ile Thr Lys Gly Gln

130 135 140

Lys Tyr Leu Phe Glu Gly Asp Met Ile Leu Asp Ser Leu Glu Ala Ile

145 150 155 160

Glu Lys Arg Arg Leu Arg Leu Gly Leu Pro Glu Ile Leu Ile Thr Gly

165 170 175

Leu Ser Pro Ile Leu Asp Val Ala Leu Leu Gln Ile Glu Ser Leu Ala

180 185 190

Arg Leu Arg Gly Met Ser Leu Asn His His Leu Phe Thr Ser Ser Ser

195 200 205

Leu Arg Lys Pro Leu Leu Asp Cys Trp Asp Phe Phe Ile Pro Ile Arg

210 215 220

Lys Lys Lys Thr Asp Gly Ser Tyr Ser Val Leu Asp Glu Asp Asp Glu

225 230 235 240

Pro Gly Ile Leu Gln Gly Tyr Pro Tyr Leu Met Ala His Tyr Leu Asn

245 250 255

Arg Cys Pro Phe His Asn Leu Ile Arg Phe Asp Glu Glu Leu Arg Thr

260 265 270

Ala Ala Leu Asn Thr Ile Trp Gly Arg Asp Trp Pro Ala Ile Gly Asp

275 280 285

Leu Pro Lys Glu Val ***

290

<210> 21

<211> 2085

<212> PRT

<213> 未知

<220>

<223> 发热伴血小板减少综合征病毒B-3 L

<400> 21

Met Asn Leu Glu Val Leu Cys Gly Arg Ile Asn Val Glu Asn Gly Leu

1 5 10 15

Ser Leu Gly Glu Pro Gly Leu Tyr Asp Gln Ile Tyr Asp Arg Pro Gly

20 25 30

Leu Pro Asp Leu Asp Val Thr Val Asp Ala Ile Gly Val Thr Val Asp

35 40 45

Ile Gly Ala Val Pro Asp Ser Ala Ser Gln Leu Gly Ser Ser Ile Asn

50 55 60

Ala Gly Leu Ile Thr Ile Gln Leu Ser Glu Ala Tyr Lys Ile Asn His

65 70 75 80

Asp Phe Thr Phe Ser Gly Leu Ser Lys Thr Thr Asp Arg Arg Leu Ser

85 90 95

Glu Val Phe Pro Ile Thr His Asp Gly Ser Asp Gly Met Thr Pro Asp

100 105 110

Val Ile His Thr Arg Leu Asp Gly Thr Ile Val Val Val Glu Phe Ser

115 120 125

Thr Thr Arg Ser His Asn Ile Gly Gly Leu Glu Ala Ala Tyr Arg Thr

130 135 140

Lys Ile Glu Lys Tyr Arg Asp Pro Ile Ser Arg Arg Val Asp Ile Met

145 150 155 160

Glu Asn Pro Arg Val Phe Phe Gly Val Ile Val Val Ser Ser Gly Gly

165 170 175

Val Leu Ser Asn Met Pro Leu Thr Gln Asp Glu Ala Glu Glu Leu Met

180 185 190

Tyr Arg Phe Cys Ile Ala Asn Glu Ile Tyr Thr Lys Ala Arg Ser Met

195 200 205

Asp Ala Asp Ile Glu Leu Gln Lys Ser Glu Glu Glu Leu Glu Ala Ile

210 215 220

Ser Arg Ala Leu Ser Phe Phe Ser Leu Phe Glu Pro Asn Ile Glu Arg

225 230 235 240

Val Glu Gly Thr Phe Pro Asn Ser Glu Ile Glu Met Leu Glu Gln Phe

245 250 255

Leu Ser Thr Pro Ala Asp Val Asp Phe Ile Thr Lys Thr Leu Lys Ala

260 265 270

Lys Glu Val Glu Ala Tyr Ala Asp Leu Cys Asp Ser His Tyr Leu Lys

275 280 285

Pro Glu Lys Thr Ile Gln Glu Arg Leu Glu Ile Asn Arg Cys Glu Ala

290 295 300

Ile Asp Lys Thr Gln Asp Leu Leu Ala Ser Leu His Ala Arg Ser Asn

305 310 315 320

Lys Gln Thr Ser Leu Asn Arg Gly Thr Val Lys Leu Pro Pro Trp Leu

325 330 335

Pro Lys Pro Ser Ser Glu Ser Ile Asp Ile Lys Thr Asp Ser Gly Phe

340 345 350

Gly Ser Leu Met Asp His Gly Thr Tyr Gly Glu Leu Trp Ala Lys Cys

355 360 365

Leu Leu Asp Val Ser Leu Gly Asn Val Glu Gly Val Val Ser Asp Pro

370 375 380

Ala Lys Glu Leu Asp Ile Ala Ile Ser Asp Asp Pro Glu Lys Asp Thr

385 390 395 400

Pro Lys Glu Ala Lys Ile Thr Tyr Arg Arg Phe Lys Pro Ala Leu Ser

405 410 415

Ser Ser Ala Arg Gln Glu Phe Ser Leu Gln Gly Val Glu Gly Lys Lys

420 425 430

Trp Lys Arg Met Ala Ala Asn Gln Lys Lys Glu Lys Glu Ser His Glu

435 440 445

Thr Leu Ser Pro Phe Leu Asp Val Glu Asp Ile Gly Asp Phe Leu Thr

450 455 460

Phe Asn Asn Leu Leu Ala Asp Ser Arg Tyr Gly Asp Glu Ser Val Gln

465 470 475 480

Arg Ala Val Ser Ile Leu Leu Glu Lys Ala Ser Ala Met Gln Asp Thr

485 490 495

Glu Leu Thr His Ala Leu Asn Asp Ser Phe Lys Arg Asn Leu Ser Ser

500 505 510

Asn Val Val Gln Trp Ser Leu Trp Val Ser Cys Leu Ala Gln Glu Leu

515 520 525

Ala Ser Ala Leu Lys Gln His Cys Arg Ala Gly Glu Phe Ile Ile Lys

530 535 540

Lys Leu Lys Phe Trp Pro Ile Tyr Val Ile Ile Lys Pro Thr Lys Ser

545 550 555 560

Ser Ser His Ile Phe Tyr Ser Leu Gly Ile Arg Lys Ala Asp Val Thr

565 570 575

Arg Arg Leu Thr Gly Arg Val Phe Ser Asp Thr Ile Asp Ala Gly Glu

580 585 590

Trp Glu Leu Thr Glu Phe Lys Ser Leu Lys Thr Cys Lys Leu Thr Asn

595 600 605

Leu Val Asn Leu Pro Cys Thr Met Leu Asn Ser Ile Ala Phe Trp Arg

610 615 620

Glu Lys Leu Gly Val Ala Pro Trp Leu Val Arg Lys Pro Cys Ser Glu

625 630 635 640

Leu Arg Glu Gln Val Gly Leu Thr Phe Leu Ile Ser Leu Glu Asp Lys

645 650 655

Ser Lys Thr Glu Glu Ile Ile Thr Leu Thr Arg Tyr Thr Gln Met Glu

660 665 670

Gly Phe Val Ser Pro Pro Met Leu Pro Lys Pro Gln Lys Met Leu Gly

675 680 685

Lys Leu Asp Gly Pro Leu Arg Thr Lys Leu Gln Val Tyr Leu Leu Arg

690 695 700

Lys His Leu Asp Cys Met Val Arg Ile Ala Ser Gln Pro Phe Ser Leu

705 710 715 720

Ile Pro Arg Glu Gly Arg Val Glu Trp Gly Gly Thr Phe His Ala Ile

725 730 735

Ser Gly Arg Ser Thr Asn Leu Glu Asn Met Val Asn Ser Trp Tyr Ile

740 745 750

Gly Tyr Tyr Lys Asn Lys Glu Glu Ser Thr Glu Leu Asn Ala Leu Gly

755 760 765

Glu Met Tyr Lys Lys Ile Val Glu Met Glu Glu Asp Lys Pro Ser Ser

770 775 780

Pro Lys Phe Leu Gly Trp Gly Asp Thr Asp Ser Pro Lys Lys His Glu

785 790 795 800

Phe Ser Arg Ser Phe Leu Arg Ala Ala Cys Ser Ser Leu Glu Arg Glu

805 810 815

Ile Ala Gln Arg His Gly Arg Gln Trp Lys Gln Asn Leu Glu Glu Arg

820 825 830

Val Leu Arg Glu Ile Gly Thr Lys Asn Ile Leu Asp Leu Ala Ser Met

835 840 845

Lys Ala Thr Ser Asn Phe Ser Lys Asp Trp Glu Leu Tyr Ser Glu Val

850 855 860

Gln Thr Lys Glu Tyr His Arg Ser Lys Leu Leu Glu Lys Met Ala Thr

865 870 875 880

Leu Ile Glu Lys Gly Val Met Trp Tyr Ile Asp Ala Val Gly Gln Ala

885 890 895

Trp Lys Ala Val Leu Asp Asp Gly Cys Met Arg Ile Cys Leu Phe Lys

900 905 910

Lys Asn Gln His Gly Gly Leu Arg Glu Ile Tyr Val Met Asp Ala Asn

915 920 925

Ala Arg Leu Val Gln Phe Gly Val Glu Thr Met Ala Arg Cys Val Cys

930 935 940

Glu Leu Ser Pro His Glu Thr Val Ala Asn Pro Arg Leu Lys Asn Ser

945 950 955 960

Ile Ile Glu Asn His Gly Leu Lys Ser Ala Arg Ser Leu Gly Pro Gly

965 970 975

Ser Ile Asn Ile Asn Ser Ser Asn Asp Ala Lys Lys Trp Asn Gln Gly

980 985 990

His Tyr Thr Thr Lys Leu Ala Leu Val Leu Cys Trp Phe Met Pro Ala

995 1000 1005

Lys Phe His Arg Phe Ile Trp Ala Ala Ile Ser Met Phe Arg Arg Lys

1010 1015 1020

Lys Met Met Val Asp Leu Arg Phe Leu Ala His Leu Ser Ser Lys Ser

1025 1030 1035 1040

Glu Ser Arg Ser Ser Asp Pro Phe Arg Glu Ala Met Thr Asp Ala Phe

1045 1050 1055

His Gly Asn Arg Glu Val Ser Trp Met Asp Lys Gly Arg Thr Tyr Ile

1060 1065 1070

Lys Thr Glu Thr Gly Met Met Gln Gly Ile Leu His Phe Thr Ser Ser

1075 1080 1085

Leu Leu His Ser Cys Val Gln Ser Phe Tyr Lys Ser Tyr Phe Val Ser

1090 1095 1100

Lys Leu Lys Glu Gly Tyr Met Gly Glu Ser Ile Ser Gly Val Val Asp

1105 1110 1115 1120

Val Ile Glu Gly Ser Asp Asp Ser Ala Ile Met Ile Ser Ile Arg Pro

1125 1130 1135

Lys Ser Asp Met Asp Glu Val Arg Ser Arg Phe Phe Val Ala Asn Leu

1140 1145 1150

Leu His Ser Val Lys Phe Leu Asn Pro Leu Phe Gly Ile Tyr Ser Ser

1155 1160 1165

Glu Lys Ser Thr Val Asn Thr Val Tyr Cys Val Glu Tyr Asn Ser Glu

1170 1175 1180

Phe His Phe His Arg His Leu Val Arg Pro Thr Leu Arg Trp Ile Ala

1185 1190 1195 1200

Ala Ser His Gln Ile Ser Glu Thr Glu Ala Leu Ala Ser Arg Gln Glu

1205 1210 1215

Asp Tyr Ser Asn Leu Leu Thr Gln Cys Leu Glu Gly Gly Ala Ser Phe

1220 1225 1230

Ser Leu Thr Tyr Leu Ile Gln Cys Ala Gln Leu Leu His His Tyr Met

1235 1240 1245

Leu Leu Gly Leu Cys Leu His Pro Leu Phe Gly Thr Phe Met Gly Met

1250 1255 1260

Leu Ile Ser Asp Pro Asp Pro Ala Leu Gly Phe Phe Leu Met Asp Asn

1265 1270 1275 1280

Pro Ala Phe Ala Gly Gly Ala Gly Phe Arg Phe Asn Leu Trp Arg Ala

1285 1290 1295

Cys Lys Thr Thr Asp Leu Gly Arg Lys Tyr Ala Tyr Tyr Phe Asn Glu

1300 1305 1310

Ile Gln Gly Lys Thr Lys Gly Asp Glu Asp Tyr Arg Ala Leu Asp Ala

1315 1320 1325

Thr Ser Gly Gly Thr Leu Ser His Ser Val Met Val Tyr Trp Gly Asp

1330 1335 1340

Arg Lys Lys Tyr Gln Ala Leu Leu Asn Arg Met Gly Leu Pro Glu Asp

1345 1350 1355 1360

Trp Val Glu Gln Ile Asp Glu Asn Pro Gly Val Leu Tyr Arg Arg Ala

1365 1370 1375

Ala Asn Lys Lys Glu Leu Leu Leu Lys Leu Ala Glu Lys Val His Ser

1380 1385 1390

Pro Gly Val Thr Ser Ser Leu Ser Lys Gly His Val Val Pro Arg Val

1395 1400 1405

Val Ala Ala Gly Val Tyr Leu Leu Ser Arg His Cys Phe Arg Phe Ser

1410 1415 1420

Ser Ser Ile His Gly Arg Gly Ser Ala Gln Lys Ala Ser Leu Ile Lys

1425 1430 1435 1440

Leu Leu Met Met Ser Ser Ile Ser Ala Met Lys His Gly Gly Ser Leu

1445 1450 1455

Asn Pro Asn Gln Glu Arg Met Leu Phe Pro Gln Ala Gln Glu Tyr Asp

1460 1465 1470

Arg Val Cys Thr Leu Leu Glu Glu Val Glu His Leu Thr Gly Lys Phe

1475 1480 1485

Val Val Arg Glu Arg Asn Ile Val Arg Ser Arg Ile Asp Leu Phe Gln

1490 1495 1500

Glu Pro Val Asp Leu Arg Cys Lys Ala Glu Asp Leu Val Ser Glu Val

1505 1510 1515 1520

Trp Phe Gly Leu Lys Arg Thr Lys Leu Gly Pro Arg Leu Leu Lys Glu

1525 1530 1535

Glu Trp Asp Lys Leu Arg Ala Ser Phe Ala Trp Leu Ser Thr Asp Pro

1540 1545 1550

Ser Glu Thr Leu Arg Asp Gly Pro Phe Leu Ser His Val Gln Phe Arg

1555 1560 1565

Asn Phe Ile Ala His Val Asp Ala Lys Ser Arg Ser Val Arg Leu Leu

1570 1575 1580

Gly Ala Pro Val Lys Lys Ser Gly Gly Val Thr Thr Ile Ser Gln Val

1585 1590 1595 1600

Val Arg Met Asn Phe Phe Pro Gly Phe Ser Leu Glu Ala Glu Lys Ser

1605 1610 1615

Leu Asp Asn Gln Glu Arg Leu Glu Ser Ile Ser Ile Leu Lys His Val

1620 1625 1630

Leu Phe Met Val Leu Asn Gly Pro Tyr Thr Glu Glu Tyr Lys Leu Asp

1635 1640 1645

Met Ile Ile Glu Ala Phe Ser Thr Leu Val Ile Pro Gln Pro Ser Glu

1650 1655 1660

Val Ile Arg Lys Ser Arg Thr Met Thr Leu Cys Leu Leu Ser Asn Tyr

1665 1670 1675 1680

Leu Ser Ser Arg Gly Gly Ser Ile Leu Asp Gln Ile Glu Arg Ala Gln

1685 1690 1695

Ser Gly Thr Leu Gly Gly Phe Ser Lys Pro Gln Lys Thr Phe Ile Arg

1700 1705 1710

Pro Gly Gly Gly Ile Gly Tyr Lys Gly Lys Gly Val Trp Thr Gly Val

1715 1720 1725

Met Glu Asp Thr His Val Gln Ile Leu Ile Asp Gly Asp Gly Thr Ser

1730 1735 1740

Asn Trp Leu Glu Glu Ile Arg Leu Ser Ser Asp Ala Arg Leu Tyr Asp

1745 1750 1755 1760

Val Ile Glu Ser Ile Arg Arg Leu Cys Asp Asp Leu Gly Ile Asn Asn

1765 1770 1775

Arg Val Ala Ser Ala Tyr Arg Gly His Cys Met Val Arg Leu Ser Gly

1780 1785 1790

Phe Lys Ile Lys Pro Ala Ser Arg Thr Asp Gly Cys Pro Val Arg Ile

1795 1800 1805

Met Glu Arg Gly Phe Arg Ile Arg Glu Leu Gln Asn Pro Asp Glu Val

1810 1815 1820

Lys Met Arg Val Arg Gly Asp Ile Leu Asn Leu Ser Val Thr Ile Gln

1825 1830 1835 1840

Glu Gly Arg Val Met Asn Ile Leu Ser Tyr Arg Pro Arg Asp Thr Asp

1845 1850 1855

Ile Ser Glu Ser Ala Ala Ala Tyr Leu Trp Ser Asn Arg Asp Leu Phe

1860 1865 1870

Ser Phe Gly Lys Lys Glu Pro Ser Cys Ser Trp Ile Cys Leu Lys Thr

1875 1880 1885

Leu Asp Asn Trp Ala Trp Ser His Ala Ser Val Leu Leu Ala Asn Asp

1890 1895 1900

Arg Lys Thr Gln Gly Ile Asp Asn Arg Ala Met Gly Asn Ile Phe Arg

1905 1910 1915 1920

Asp Cys Leu Glu Gly Ser Leu Arg Lys Gln Gly Leu Met Arg Ser Lys

1925 1930 1935

Leu Thr Glu Met Val Glu Lys Asn Val Val Pro Leu Thr Thr Gln Glu

1940 1945 1950

Leu Val Asp Ile Leu Glu Glu Asp Ile Asp Phe Ser Asp Val Ile Ala

1955 1960 1965

Val Glu Leu Ser Glu Gly Ser Leu Asp Ile Glu Ser Ile Phe Asp Gly

1970 1975 1980

Ala Pro Ile Leu Trp Ser Ala Glu Val Glu Glu Phe Gly Glu Gly Val

1985 1990 1995 2000

Val Ala Val Ser Tyr Ser Ser Lys Tyr Tyr His Leu Thr Leu Met Asp

2005 2010 2015

Gln Ala Ala Ile Thr Met Cys Ala Ile Met Gly Lys Glu Gly Cys Arg

2020 2025 2030

Gly Leu Leu Thr Glu Lys Arg Cys Met Ala Ala Ile Arg Glu Gln Val

2035 2040 2045

Arg Pro Phe Leu Ile Phe Leu Gln Ile Pro Glu Asp Ser Ile Ser Trp

2050 2055 2060

Val Ser Asp Gln Phe Cys Asp Ser Arg Gly Leu Asp Glu Glu Ser Thr

2065 2070 2075 2080

Ile Met Trp Gly ***

2085

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<400> 22

Met Met Lys Val Ile Trp Phe Ser Ser Leu Ile Cys Leu Val Ile Gln

1 5 10 15

Cys Ser Gly Asp Thr Gly Pro Ile Ile Cys Ala Gly Pro Ile His Ser

20 25 30

Asn Lys Ser Ala Asn Ile Pro His Leu Leu Gly Tyr Ser Glu Lys Ile

35 40 45

Cys Gln Ile Asp Arg Leu Ile His Val Ser Ser Trp Leu Arg Asn His

50 55 60

Ser Gln Phe Gln Gly Tyr Val Gly Gln Arg Gly Gly Arg Ser Gln Val

65 70 75 80

Ser Tyr Tyr Pro Ala Glu Asn Ser Tyr Ser Arg Trp Ser Gly Leu Leu

85 90 95

Ser Pro Cys Asp Ala Asp Trp Leu Gly Met Leu Val Val Lys Lys Ala

100 105 110

Lys Gly Ser Asp Met Ile Val Pro Gly Pro Ser Tyr Lys Gly Lys Val

115 120 125

Phe Phe Glu Arg Pro Thr Phe Asp Gly Tyr Val Gly Trp Gly Cys Gly

130 135 140

Ser Gly Lys Ser Arg Thr Glu Ser Gly Glu Leu Cys Ser Ser Asp Ser

145 150 155 160

Gly Thr Ser Ser Gly Leu Leu Pro Ser Asn Arg Val Leu Trp Ile Gly

165 170 175

Asp Val Ala Cys Gln Pro Met Thr Pro Ile Pro Glu Glu Thr Phe Leu

180 185 190

Glu Leu Lys Ser Phe Ser Gln Ser Glu Phe Pro Asp Ile Cys Lys Val

195 200 205

Asp Gly Ile Val Phe Asn Gln Cys Glu Ser Glu Ser Leu Pro Gln Pro

210 215 220

Phe Asp Val Ala Trp Met Asp Val Gly His Ser His Lys Ile Ile Met

225 230 235 240

Arg Glu His Lys Thr Lys Trp Val Gln Glu Ser Ser Ser Lys Asp Phe

245 250 255

Val Cys Tyr Lys Glu Gly Thr Gly Pro Cys Ser Glu Ser Glu Glu Lys

260 265 270

Thr Cys Lys Thr Ser Gly Ser Cys Arg Gly Asp Met Gln Phe Cys Lys

275 280 285

Val Ala Gly Cys Glu His Gly Glu Glu Ala Ser Glu Ala Lys Cys Arg

290 295 300

Cys Ser Leu Val His Lys Pro Gly Glu Val Val Val Ser Tyr Gly Gly

305 310 315 320

Met Arg Val Arg Pro Lys Cys Tyr Gly Phe Ser Arg Met Met Ala Thr

325 330 335

Leu Glu Val Asn Pro Pro Glu Gln Arg Ile Gly Gln Cys Thr Gly Cys

340 345 350

His Leu Glu Cys Ile Asn Gly Gly Val Arg Leu Ile Thr Leu Thr Ser

355 360 365

Glu Leu Lys Ser Ala Thr Val Cys Ala Ser His Phe Cys Ser Ser Ala

370 375 380

Thr Ser Gly Lys Lys Ser Thr Glu Ile Gln Phe His Ser Gly Ser Leu

385 390 395 400

Val Gly Lys Ala Ala Ile His Val Lys Gly Thr Leu Val Asp Gly Thr

405 410 415

Glu Phe Thr Phe Glu Gly Ser Cys Met Phe Pro Asp Gly Cys Asp Ala

420 425 430

Val Asp Cys Thr Phe Cys Arg Glu Phe Leu Lys Asn Pro Gln Cys Tyr

435 440 445

Pro Ala Lys Lys Trp Leu Phe Ile Ile Ile Ala Ile Leu Leu Gly Tyr

450 455 460

Ala Gly Leu Met Leu Leu Thr Asn Val Leu Lys Ala Ile Gly Val Trp

465 470 475 480

Gly Ser Trp Val Ile Ala Pro Val Lys Leu Met Phe Ala Ile Ile Lys

485 490 495

Lys Leu Met Arg Ser Val Ser Cys Leu Met Gly Lys Leu Met Asp Arg

500 505 510

Gly Arg Gln Val Ile His Glu Glu Ile Gly Glu Asn Arg Glu Gly Asn

515 520 525

Gln Glu Asp Val Arg Ile Glu Ile Ala Arg Pro Arg Arg Val Arg His

530 535 540

Trp Met Tyr Ser Pro Val Ile Leu Ala Ile Leu Ala Ile Gly Leu Ala

545 550 555 560

Glu Gly Cys Asp Glu Met Val His Ala Asp Ser Lys Leu Val Ser Cys

565 570 575

Arg Gln Gly Ser Gly Asn Met Lys Glu Cys Val Thr Thr Gly Arg Ala

580 585 590

Leu Leu Pro Ala Val Asn Pro Gly Gln Glu Ala Cys Leu His Phe Thr

595 600 605

Ala Pro Gly Ser Pro Asp Ser Lys Cys Leu Lys Ile Lys Val Lys Arg

610 615 620

Ile Asn Leu Lys Cys Lys Lys Ser Ser Ser Tyr Phe Val Pro Asp Ala

625 630 635 640

Arg Ser Arg Cys Thr Ser Val Arg Arg Cys Arg Trp Ala Gly Asp Cys

645 650 655

Gln Ser Gly Cys Pro Ser His Phe Thr Ser Asn Ser Phe Ser Asp Asp

660 665 670

Trp Ala Gly Lys Met Asp Arg Ala Gly Leu Gly Phe Ser Gly Cys Ser

675 680 685

Asp Gly Cys Gly Gly Ala Ala Cys Gly Cys Phe Asn Ala Ala Pro Ser

690 695 700

Cys Ile Phe Trp Arg Lys Trp Val Glu Asn Pro His Gly Ile Ile Trp

705 710 715 720

Lys Val Ser Pro Cys Ala Ala Trp Val Pro Ser Thr Val Ile Glu Leu

725 730 735

Thr Met Pro Ser Gly Glu Val Arg Thr Phe His Pro Met Ser Gly Ile

740 745 750

Pro Thr Gln Val Phe Lys Gly Val Ser Val Thr Tyr Leu Gly Ser Asp

755 760 765

Met Glu Val Ser Gly Leu Thr Asp Leu Cys Glu Ile Glu Glu Leu Lys

770 775 780

Ser Lys Lys Leu Ala Leu Ala Pro Cys Asn Gln Ala Gly Met Gly Val

785 790 795 800

Val Gly Lys Val Gly Glu Ile Gln Cys Ser Ser Glu Glu Ser Ala Arg

805 810 815

Ser Ile Lys Lys Asp Gly Cys Ile Trp Asn Ala Asp Leu Val Gly Ile

820 825 830

Glu Leu Arg Val Asp Asp Ala Val Cys Tyr Ser Lys Ile Thr Ser Val

835 840 845

Glu Ala Val Ala Asn Tyr Ser Ala Ile Pro Thr Thr Ile Gly Gly Leu

850 855 860

Arg Phe Glu Arg Ser His Asp Ser Gln Gly Lys Ile Ser Gly Ser Pro

865 870 875 880

Leu Asp Ile Thr Ala Ile Arg Gly Ser Phe Ser Val Asn Tyr Arg Gly

885 890 895

Leu Arg Leu Ser Leu Ser Glu Ile Thr Ala Thr Cys Thr Gly Glu Val

900 905 910

Thr Asn Val Ser Gly Cys Tyr Ser Cys Met Thr Gly Ala Lys Val Ser

915 920 925

Ile Lys Leu His Ser Ser Lys Asn Ser Thr Ala His Val Arg Cys Lys

930 935 940

Gly Asp Glu Thr Ala Phe Ser Val Leu Glu Gly Val His Ser Tyr Thr

945 950 955 960

Val Ser Leu Ser Phe Asp His Ala Val Val Asp Glu Gln Cys Gln Leu

965 970 975

Asn Cys Gly Gly His Glu Ser Gln Val Thr Leu Lys Gly Asn Leu Ile

980 985 990

Phe Leu Asp Val Pro Lys Phe Val Asp Gly Ser Tyr Met Gln Thr Tyr

995 1000 1005

His Ser Ser Val Pro Thr Gly Ala Asn Ile Pro Ser Pro Thr Asp Trp

1010 1015 1020

Leu Asn Ala Leu Phe Gly Asn Gly Leu Ser Arg Trp Ile Leu Gly Val

1025 1030 1035 1040

Ile Gly Val Leu Leu Gly Gly Leu Ala Leu Phe Phe Leu Ile Met Ser

1045 1050 1055

Leu Phe Lys Leu Gly Thr Lys Gln Ile Phe Arg Ser Arg Thr Lys Leu

1060 1065 1070

Ala ***

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Met Ser Glu Trp Ser Arg Ile Ala Val Glu Phe Gly Glu Gln Gln Leu

1 5 10 15

Asn Leu Thr Glu Leu Glu Asp Phe Ala Arg Glu Leu Ala Tyr Glu Gly

20 25 30

Leu Asp Pro Ala Leu Ile Ile Lys Lys Leu Lys Glu Thr Gly Gly Asp

35 40 45

Asp Trp Val Arg Asp Thr Lys Phe Ile Ile Val Phe Ala Leu Thr Arg

50 55 60

Gly Asn Lys Ile Val Lys Ala Ser Gly Lys Met Ser Asn Ser Gly Ser

65 70 75 80

Lys Arg Leu Met Ala Leu Gln Glu Lys Tyr Gly Leu Val Glu Arg Ala

85 90 95

Glu Thr Arg Leu Ser Ile Thr Pro Val Arg Val Ala Gln Ser Leu Pro

100 105 110

Thr Trp Thr Cys Ala Ala Ala Ala Ala Leu Lys Glu Tyr Leu Pro Val

115 120 125

Gly Pro Ala Val Met Asn Leu Lys Val Glu Asn Tyr Pro Pro Glu Met

130 135 140

Met Cys Met Ala Phe Gly Ser Leu Ile Pro Thr Ala Gly Val Ser Glu

145 150 155 160

Ala Thr Thr Lys Thr Leu Met Glu Ala Tyr Ser Leu Trp Gln Asp Ala

165 170 175

Phe Thr Lys Thr Ile Asn Val Lys Met Arg Gly Ala Ser Lys Thr Glu

180 185 190

Val Tyr Asn Ser Phe Arg Asp Pro Leu His Ala Ala Val Asn Ser Val

195 200 205

Phe Phe Pro Asn Asp Val Arg Val Lys Trp Leu Lys Ala Lys Gly Ile

210 215 220

Leu Gly Pro Asp Gly Val Pro Ser Arg Ala Ala Glu Val Ala Ala Ala

225 230 235 240

Ala Tyr Arg Asn Leu ***

245

<210> 24

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Met Ser Leu Ser Lys Cys Ser Asn Val Asp Leu Lys Ser Val Ala Met

1 5 10 15

Asn Ala Asn Thr Val Arg Leu Glu Pro Ser Leu Gly Glu Tyr Pro Thr

20 25 30

Leu Arg Lys Asp Leu Val Glu Cys Ser Cys Ser Val Leu Thr Leu Ser

35 40 45

Met Val Lys Arg Met Gly Lys Met Thr Asn Thr Val Trp Leu Phe Gly

50 55 60

Asn Pro Lys Asn Pro Leu His Gln Leu Glu Pro Gly Leu Glu Gln Leu

65 70 75 80

Leu Asp Met Tyr Tyr Lys Asp Met Arg Cys Tyr Ser Gln Arg Glu Leu

85 90 95

Ser Ala Leu Arg Trp Pro Ser Gly Lys Pro Ser Val Trp Phe Leu Gln

100 105 110

Ala Ala His Met Phe Phe Ser Ile Lys Asn Ser Trp Ala Met Glu Thr

115 120 125

Gly Arg Glu Asn Trp Arg Gly Leu Phe His Arg Ile Thr Lys Gly Lys

130 135 140

Lys Tyr Leu Phe Glu Gly Asp Met Ile Leu Asp Ser Leu Glu Ala Ile

145 150 155 160

Glu Lys Arg Arg Leu Arg Leu Gly Leu Pro Glu Ile Leu Ile Thr Gly

165 170 175

Leu Ser Pro Ile Leu Asp Val Ala Leu Leu Gln Ile Glu Ser Leu Ala

180 185 190

Arg Leu Arg Gly Met Ser Leu Asn His His Leu Phe Thr Ser Ser Ser

195 200 205

Leu Arg Lys Pro Leu Leu Asp Cys Trp Asp Phe Phe Ile Pro Ile Arg

210 215 220

Lys Lys Lys Thr Asp Gly Ser Tyr Ser Val Leu Asp Glu Asp Asp Glu

225 230 235 240

Pro Gly Val Leu Gln Gly Tyr Pro Tyr Leu Met Ala His Tyr Leu Asn

245 250 255

Arg Cys Pro Phe His Asn Leu Ile Arg Phe Asp Glu Glu Leu Arg Thr

260 265 270

Ala Ala Leu Asn Thr Ile Trp Gly Arg Asp Trp Pro Ala Ile Gly Asp

275 280 285

Leu Pro Lys Glu Val ***

290