The mechanism by which pandemic influenza A viruses emerge

大流行甲型流感病毒的出现机制

• 批准号: 20790352
• 负责人: YAMADA Shinya
• 金额: $ 2.75万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790352/
• 关键词: 新型インフルエンザ; レセプター認識

The host range restriction of influenza viruses is partly attributable to receptor specificity : most avian influenza A viruses preferentially bind to the sialic acid-α2, 3-galactose (SAα2, 3Gal) linkage on sialyloligosaccharides, whereas human viruses bind to SAα2, 6Gal. In this study, we found the positive charge of hemeggulutinin(HA) of human H3N2 viruses has been increasing year by year since they emerged in humans in 1968, resulting in the electrostatic interaction with SAα2, 6Gal, whereas there is no surface charge changes of HA proteins of avian H3N2 viruses. We also found some H5N1 viruses isolated from humans possessing mutations : substitution to basic amino acids, recognized SAα2, 6Gal in the charge dependent manner. These results suggested that charge dependent recognition of human-type receptors is one of the mechanism by which influenza viruses adapt to humans. Moreover, computational simulation of the surface charge of HA proteins appears to be available for the understanding of interaction between HA proteins and receptors. Among mutations unique to human isolates, amino acid substitution at position 182 especially increased the replicative ability of H5N1 viruses in normal human bronchus epithelial cells. However, none of H5N1 viruses tested in this study showed efficient transmission in ferret model.

流感病毒宿主范围的限制部分归因于受体的特异性：大多数禽流感病毒优先与唾液酸寡糖上的唾液酸-α2，3-半乳糖(SAα2，3Gal)结合，而人类病毒则与SAα2，6Gal结合。在本研究中，我们发现人H3N2病毒自1968年出现以来，其半乳糖素(hemegulutinin，HA)的正电荷逐年增加，与SAα2，6Gal发生静电相互作用，而禽流感H3N2病毒的HA蛋白没有表面电荷变化。我们还发现了一些从人类分离的H5N1病毒具有突变：对碱性氨基酸的替换，以电荷依赖的方式识别SAα2，6Gal。这些结果表明，对人型受体的电荷依赖识别是流感病毒适应人类的机制之一。此外，对HA蛋白表面电荷的计算模拟似乎有助于理解HA蛋白与受体之间的相互作用。在人类分离株特有的突变中，第182位氨基酸替换尤其增加了H5N1病毒在正常人支气管上皮细胞中的复制能力。然而，在这项研究中测试的H5N1病毒都没有在雪貂模型中有效传播。

项目成果

A comparison of the pathogenicity of avian and swine H5N1 influenza viruses in Indonesia

• DOI: 10.1007/s00705-009-0353-5
• 发表时间: 2009-04-01
• 期刊: ARCHIVES OF VIROLOGY
• 影响因子: 2.7
• 作者: Takano, Ryo;Nidom, Chairul A.;Kawaoka, Yoshihiro
• 通讯作者: Kawaoka, Yoshihiro

In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses.

• DOI: 10.1038/nature08260
• 发表时间: 2009-08-20
• 期刊: Nature
• 影响因子: 64.8

Medical Bio

医疗生物

• 发表时间: 2007
• 作者: Akihisa Takeuchi;Yasuko Terada;Yoshio Suzuki;Kentaro Uesugi;Sadao Aoki;君塚 信夫;浦野 泰照
• 通讯作者: 浦野 泰照

Phylogenetic characterization of H5N1 avian influenza viruses isolated in Indonesia from 2003-2007

• DOI: 10.1016/j.virol.2009.04.024
• 发表时间: 2009-07-20
• 期刊: VIROLOGY
• 影响因子: 3.7
• 作者: Takano, Ryo;Nidom, Chairul A.;Kawaoka, Yoshihiro
• 通讯作者: Kawaoka, Yoshihiro

Mutational Analysis of Conserved Amino Acids in the Influenza A Virus Nucleoprotein

• DOI: 10.1128/jvi.02642-08
• 发表时间: 2009-05-01
• 期刊: JOURNAL OF VIROLOGY
• 影响因子: 5.4
• 作者: Li, Zejun;Watanabe, Tokiko;Kawaoka, Yoshihiro
• 通讯作者: Kawaoka, Yoshihiro