The mechanism by which pandemic influenza A viruses emerge

2009 Fiscal Year Final Research Report

• Project/Area Number: 20790352
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Virology
• Research Institution: The University of Tokyo
• Principal Investigator: YAMADA Shinya The University of Tokyo, 医科学研究所, 特任研究員 (90466839)
• Project Period (FY): 2008 – 2009
• Keywords: 新型インフルエンザ / レセプター認識

Research Abstract

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.

Research Products

• [Journal Article] In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. (2009)
  • Author(s): Itoh Y, Shinya K, Kiso M, Watanabe T, Sakoda Y, Hatta M, Muramoto Y, Tamura D, Sakai-Tagawa Y, Noda T, Sakabe S, Imai M, Hatta Y, Watanabe S, Li C, Yamada S, et. al
  • Journal Title: Nature. 460(7258) Pages: 1021-5
  • Peer Reviewed
• [Journal Article] Phylogenetic characterization of H5N1 avian influenza viruses isolated in Indonesia from 2003-2007. (2009)
  • Author(s): Takano R, Nidom CA, Kiso M, Muramoto Y, Yamada S, Sakai-Tagawa Y, Macken C, Kawaoka Y.
  • Journal Title: Virology. 390(1) Pages: 13-21
  • Peer Reviewed
• [Journal Article] A comparison of the pathogenicity of avian and swine H5N1 influenza viruses in Indonesia. (2009)
  • Author(s): Takano R, Nidom CA, Kiso M, Muramoto Y, Yamada S, Shinya K, Sakai-Tagawa Y, Kawaoka Y.
  • Journal Title: Arch Virol. 154(4) Pages: 677-81
  • Peer Reviewed
• [Journal Article] Mutational analysis of conserved amino acids in the influenza A virus nucleoprotein. (2009)
  • Author(s): Li Z, Watanabe T, Hatta M, Watanabe S, Nanbo A, Ozawa M, Kakugawa S, Shimojima M, Yamada S, Neumann G, Kawaoka Y
  • Journal Title: J Virol. 83(9) Pages: 4153-62
  • Peer Reviewed
• [Journal Article] Cross-clade protective immunity of H5N1 influenza vaccines in a mouse model. (2008)
  • Author(s): Murakami S, Iwasa A, Iwatsuki-Horimoto K, Ito M, Kiso M, Kida H, Takada A, Nidom CA, Mai le Q, Yamada S, Imai H, Sakai-Tagawa Y, Kawaoka Y, Horimoto T.
  • Journal Title: Vaccine. 26(50) Pages: 6398-404
  • Peer Reviewed
• [Journal Article] Establishment of canine RNA polymerase I-driven reverse genetics for influenza A virus: its application for H5N1 vaccine production. (2008)
  • Author(s): Murakami S, Horimoto T, Mai le Q, Nidom CA, Chen H, Muramoto Y, Yamada S, Iwasa A, Iwatsuki-Horimoto K, Shimojima M, Iwata A, Kawaoka Y.
  • Journal Title: J Virol. 82(21) Pages: 10502-9
  • Peer Reviewed
• [Journal Article] Establishment of canine RNA polymerase I-driven reverse genetics for influenza A virus: its application for H5N1 vaccine production. (2008)
  • Author(s): Murakami S, Horimoto T, Yamada S, Kakugawa S, Goto H, Kawaoka Y
  • Journal Title: J Virol. 82(3) Pages: 1605-9
  • Peer Reviewed
• [Presentation]
  • Organizer: 第56回日本ウイルス学会、学術集会
  • Place of Presentation: (口頭発表)