Origin and Mutations of Hong Kong New H5 Influenza Viruses

香港新型H5流感病毒的起源和变异

• 批准号: 11694210
• 负责人: ITO Toshihiro
• 金额: $ 8.31万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11694210/
• 关键词: influenza virus; fowl plague; host range; pathogenicity; chicken; H5; pandemic; recerse genetics; 新型ウイルス; ヘマグルチニン; 開裂; レセプター

An H5N1 avian influenza A virus was transmitted to humans in Hong Kong in 1997. Although the virus causes systemic infection and is highly lethal in chickens because of the susceptibility of the hemagglutinin to furin and PC6 proteases, their virulence in mice revealed two distinct groups of viruses : group 1, for which the dose lethal for 50 % of mice (MLD_<50>) was between 0.3 and 11 PFU, and group 2, for which the MLD_<50> was more than 10^3 PFU. The failure of some H5N1 viruses to produce systemic infection in our model indicates that multiple, factors contribute to the severity of H5N1 infection in mammals. In addition, our experimental passages of a waterfowl isolate through chickens demonstrated that avirulent viruses maintained in wild waterfowl in nature have the potential to become highly pathogenic while circulating in chickens. The series of virulence mutants isolated in the present study not only lend insight into mechanisms of virulence acquisition but may also provide a useful tool, in combination with reverse genetics, with which to generate influenza viruses from plasmids.

H5N1 甲型禽流感病毒于 1997 年在香港传播给人类。虽然该病毒会引起全身感染，并且由于血凝素对弗林蛋白酶和 PC6 蛋白酶的敏感性而对鸡具有高度致死性，但它们对小鼠的毒力揭示了两种不同的病毒组：第 1 组，对 50% 小鼠的致死剂量 (MLD_<50>) 介于 0.3 和 11 PFU，以及第 2 组，其中 MLD_<50> 大于 10^3 PFU。在我们的模型中，一些 H5N1 病毒未能产生全身感染，这表明多种因素导致哺乳动物 H5N1 感染的严重程度。此外，我们对水禽分离物通过鸡进行的实验表明，自然界中野生水禽中维持的无毒病毒在鸡中传播时有可能成为高致病性。本研究中分离出的一系列毒力突变体不仅有助于深入了解毒力获得机制，而且还可能提供与反向遗传学相结合的有用工具，用于从质粒产生流感病毒。

项目成果

Ito, T.: "Host range barriar of influenza A viruses"Vet.Microbiol.. 74(1). 71-75 (2000)

Ito, T.：“甲型流感病毒的宿主范围屏障”Vet.Microbiol.. 74(1)。

Imai, M.: "Antigenic and genetic analyses of H5 influenza viruses isolated from ducks in Asia"Jpn.J.Vet.Res.. 46(4). 171-177 (2000)

Imai, M.：“从亚洲鸭子中分离出的 H5 流感病毒的抗原和遗传分析”Jpn.J.Vet.Res. 46(4)。

Peng, G.: "Biologic heterogeneity, including systemic replication, of H5N1 influenza A viruses isolated from humans in Hong Kong"J.Virol.. 73(4). 3184-3189 (1999)

Peng, G.：“从香港人类中分离出的 H5N1 甲型流感病毒的生物异质性，包括系统复制”J.Virol.. 73(4)。

Ito, T.: "Differences in receptor specificity between Newcastle disease viruses originating from chickens and waterfowl"J. Vet. Med. Sci.. 61 (8). 951-953 (1999)

Ito, T.：“源自鸡和水禽的新城疫病毒之间受体特异性的差异”J.

Takahashi, M.: "Influenza virus-induced encephalopathy : clinicopathologic study of an autopsied case"Pediatr. Int.. 42 (2). 204-214 (2000)

Takahashi, M.：“流感病毒引起的脑病：尸检病例的临床病理学研究”Pediatr。