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.

宿主病毒的宿主范围限制部分归因于受体特异性：大多数鸟类影响病毒优先与唾液酸酸-α2，3-半乳糖（SAα2，3GAL）链接在硫甘氨酸酸酯上的链接，而人类病毒与Saα2，6gal结合。在这项研究中，我们发现，自1968年在人类中出现以来，人类H3N2病毒的Hemegglutin（HA）（HA）的正电荷逐年增加，导致与Saα2，6Gal的静电相互作用，而没有AVIAN H3N2病毒的HA蛋白的表面电荷变化。我们还发现了一些从具有突变的人类中分离出来的H5N1病毒：取代碱性氨基酸，以电荷依赖性方式识别为SAα2，6GAL。这些结果表明，依赖电荷对人型受体的识别是影响Za病毒适应人类的机制之一。此外，HA蛋白表面电荷的计算模拟似乎可用于理解HA蛋白与接收器之间的相互作用。在人类分离株独有的突变中，位置182的氨基酸取代特别提高了正常人支气管上皮细胞中H5N1病毒的复制能力。然而，这项研究中未测试的H5N1病毒均显示雪貂模型中有效传播。

项目成果

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

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