Mechanism of emergence of new influenza viruses and their control

新型流感病毒的出现机制及其防治

• 批准号: 18002014
• 负责人: KAWAOKA Yoshihiro
• 金额: $ 370.24万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Specially Promoted Research
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18002014/
• 关键词: インフルエンザ; 抗ウイルス薬; 薬剤耐性ウイルス; レセプター; ウイルス粒子形成; オセルタミビル; タミフル

We studied the mechanisms by which H5N1 avian influenza viruses are transmitted to humans. We identified several amino acids that support efficient avian virus replication in mammals, and determined the distribution of avian-type receptors in the human airway. In 2009, during the term of this project, an influenza pandemic occurred. We therefore analyzed the mechanisms of the emergence of drug-resistant pandemic (H1N1) 2009 and H5N1 viruses. The data we obtained were and continue to be critical to the proper usage of influenza drugs in the clinical setting. We also analyzed the packaging mechanism of the influenza viral genome, and elucidated the three-dimensional structure of ribonucleoprotein complexes within progeny virions. The information obtained from these studies is critical for not only the prevention of future pandemics but also the development of new strategies to combat seasonal and pandemic influenza.

我们研究了H5N1禽流感病毒传播给人类的机制。我们确定了几种支持禽流感病毒在哺乳动物中高效复制的氨基酸，并确定了禽流感型受体在人类气道中的分布。2009年，在本项目期间，发生了流感大流行。因此，我们分析了耐药大流行（H1N1） 2009和H5N1病毒出现的机制。我们获得的数据对临床环境中正确使用流感药物至关重要。我们还分析了流感病毒基因组的包装机制，并阐明了子代病毒粒子内核糖核蛋白复合物的三维结构。从这些研究中获得的信息不仅对预防未来的大流行，而且对制定抗击季节性流感和大流行性流感的新战略至关重要。

项目成果

Viral Replication Rate Regulates Clinical Outcome and CD8 T Cell Responses during Highly Pathogenic H5N1 Influenza Virus Infection in Mice

• DOI: 10.1371/journal.ppat.1001139
• 发表时间: 2010-10-01
• 期刊: PLOS PATHOGENS
• 影响因子: 6.7
• 作者: Hatta, Yasuko;Hershberger, Karen;Suresh, M.
• 通讯作者: Suresh, M.

Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice

• DOI: 10.1016/j.virol.2008.11.044
• 发表时间: 2009-02-05
• 期刊: VIROLOGY
• 影响因子: 3.7
• 作者: Fan, Shufang;Deng, Guohua;Chen, Hualan
• 通讯作者: Chen, Hualan

Efficient vagina-to-lower respiratory tract immune trafficking in a murine model of influenza A virus infection

• DOI: 10.1016/j.virol.2006.12.001
• 发表时间: 2007-05-10
• 期刊: VIROLOGY
• 影响因子: 3.7
• 作者: Garulli, Bruno;Meola, Monica;Castrucci, Maria Rita
• 通讯作者: Castrucci, Maria Rita

Hierarchy among vRNA segments in their role in vRNA incorporation into influenza A virions.

vRNA 片段在 vRNA 掺入甲型流感病毒颗粒中的作用的层次结构。

• 发表时间: 2006
• 期刊: Journal of Virology 80
• 作者: Muramoto Y.;et al.
• 通讯作者: et al.

Enigmas of influenza

流感之谜

• 发表时间: 2007
• 作者: K. Araki;T. Yoshikawa;M. Akatsu;I. Ishii;Y. Nemoto;T. Goto;H. S. Suzuki;41. Tanida and S. Takagi;河岡義裕
• 通讯作者: 河岡義裕