Influenza virus : the mechanism of genome packaging

• Project/Area Number: 14021013
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: University of Tokyo
• Principal Investigator: KAWAOKA Yoshihiro University of Tokyo, Institute of Medical Science, Professor, 医科学研究所, 教授 (70135838)
• Project Period (FY): 2002 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥66,000,000 (Direct Cost: ¥66,000,000); Fiscal Year 2005: ¥15,000,000 (Direct Cost: ¥15,000,000); Fiscal Year 2004: ¥15,000,000 (Direct Cost: ¥15,000,000); Fiscal Year 2003: ¥18,000,000 (Direct Cost: ¥18,000,000); Fiscal Year 2002: ¥18,000,000 (Direct Cost: ¥18,000,000)
• Keywords: virus / influenza virus / genome / packaging / reverse genetics / ゲノムRNA / ゲノムパッケージング / パッケージングシグナル / NS蛋白質 / パッケージング・シグナル / NA蛋白質 / HA蛋白質

Research Abstract

The genome of influenza A viruses comprises eight negative-strand RNA segments. Although all eight segments must be present in cells for efficient viral replication, the mechanism(s) by which these viral RNA (vRNA) segments are incorporate into virions is not fully understood. In this study, we found that sequences at both ends of the coding and noncoding regions of all eight segments of A/WSN/33 play important roles in the incorporation of these vRNAs into influenza virions. Indeed, electron microscopy of influenza A virus has revealed that budding virions contain eight ribonucleoprotein (RNP) molecules, indicating that the RNPs likely assemble to form a multisegmented macromolecule. These findings indicated that the genome packaging steps could be excellent targets for the development of antiviral compounds.

Research Products

• [Journal Article] Hierarcy amang vRNA segments in their role in vRNA incorporation into influenza A virions. (2006)
  • Author(s): Muramoto, Y., et al.
  • Journal Title: J.Virol. 80 Pages: 2318-2325
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Architecture of ribonucleoprotein complexes in influenza A virus partickes. (2006)
  • Author(s): Noda, T., et al.
  • Journal Title: Nature 439 Pages: 490-492
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Y Hierarchy among vRNA segments in their role in vRNA incorporation into influenza A virions. (2006)
  • Author(s): Muramoto, Y, Takada, A., Fujii, K., Noda, T., Iwatsuki- Horimoto, K., Watanabe, S., Horimoto, T., Kida, H., Kawaoka
  • Journal Title: J. Virol. 80 Pages: 2318-2325
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Y Architecture of ribonucleoprotein complexes in influenza A virus particles. (2006)
  • Author(s): Noda, T., Sagara, H., Yen, A., Takada, A., Kida, A., Cheng, RH., Kawaoka
  • Journal Title: Nature 439 Pages: 490-492
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Architecture of ribonucleoprotein complexes in influenza A virus particles (2006)
  • Author(s): Noda et al.
  • Journal Title: Nature 439 Pages: 490-490
• [Journal Article] Hierarchy among viral RNA (vRNA) segments in their role in vRNA incorporation into influenza A virions. (2006)
  • Author(s): Muramoto et al.
  • Journal Title: J.Virol. 80 Pages: 2318-2318
• [Journal Article] Importance of both the coding and the segment-specific noncoding regious of the influenza A virus NS segment for its efficient incorporation ito virious. (2005)
  • Author(s): Fujii, Y., et al.
  • Journal Title: J.Virol. 79 Pages: 3766-3774
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Y Importance of both the coding and the segment-specific noncoding resions of the influenza A virus NS segment for its efficient incorporation into virions. (2005)
  • Author(s): Fujii, K., Fujii, Y, Noda, T., Muramoto, Y, Watanabe, T., Takada, A., Goto, H., Horimoto, T., Kawaoka
  • Journal Title: J. Virol. 79 Pages: 3766-3774
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Avian flu : isolation of drug-resistant H5N1 virus. (2005)
  • Author(s): Le et al.
  • Journal Title: Nature 437 Pages: 754-754
• [Journal Article] An improved reverse genetics system for influenza A virus generation and its implications for vaccine production. (2005)
  • Author(s): Neumann et al.
  • Journal Title: Proc.Natl.Acad.Sci. 102 Pages: 16825-16825
• [Journal Article] Importance of both the coding and the segment-specific noncoding regions of the influenza A virus NS segment for its efficient incorporation into virions. (2005)
  • Author(s): Fujii et al.
  • Journal Title: J.Virol. 79 Pages: 3776-3776
• [Journal Article] Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus. (2004)
  • Author(s): Kobasa D, Takada A, Shinya K, Kawaoka Y et al.
  • Journal Title: Nature 431 Pages: 703-707
• [Journal Article] Resistant influenza A viruses in children treated with oseltamivir : descriptive study. (2004)
  • Author(s): Kiso M, Mitamura K, Sakai-Tagawa Y, Kawaoka Y et al.
  • Journal Title: Lancet 364 Pages: 759-765
• [Journal Article] The index influenza A virus subtype H5N1 isolated from a human in 1997 differs in its receptor binding properties from a virulent avian influenza virus. (2004)
  • Author(s): Iwatsuki-Horimoto K, Kanazawa R, Sugii S, Kawaoka Y et al.
  • Journal Title: J Gen Virol 85 Pages: 1001-1005
• [Journal Article] PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. (2004)
  • Author(s): Shinya K, Hamm S, Hatta M, Ito H, Ito T, Kawaoka Y.
  • Journal Title: Virology 320 Pages: 258-266
• [Journal Article] Characterization of a neuraminidase-deficient influenza A virus as a potential gene delivery vector and a live vaccine. (2004)
  • Author(s): Shinya K, Fujii Y, Ito H, Ito T, Kawaoka Y.
  • Journal Title: J Virol 78 Pages: 3083-3088
• [Journal Article] Generation of influenza A virus NS2 (NEP) mutants with an altered nuclear export signal sequence. (2004)
  • Author(s): Iwatsuki-Horimoto K, Horimoto T, Fujii Y, Kawaoka Y.
  • Journal Title: J Virol 78 Pages: 10149-10155
• [Journal Article] Selective incorporation of influenza virus RNA segments into virions. (2003)
  • Author(s): Fujii, Y., et al.
  • Journal Title: Proc.Natl.Acad.Sci.USA 100 Pages: 2002-2007
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Exploitation of nucleic acid packaging signals to generate a novel influenza virus-based vector stably expressing two foreign genes. (2003)
  • Author(s): Watanabe, T., et al.
  • Journal Title: J.Virol. 77 Pages: 10575-10583
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Selective incorporation of influenza virus RNA segments into virions. (2003)
  • Author(s): Fujii, Y, Goto, H., Watanabe, T., Yoshida, T., Kawaoka, Y
  • Journal Title: Proc. Natl. Acad. Sci. USA 100 Pages: 2002-2007
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Exploitation of nucleic acid packaging signals to generate a novel influenza virus-based vector stably expressing two foreign genes. (2003)
  • Author(s): Watanabe, T., Watanabe, S., Noda, T., Fujii, Y, Kawaoka Y
  • Journal Title: J. Virol. 77 Pages: 10575-10583
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The cytoplasmic taiI of the influenza A virus M2 protein plays a role in viral assembly
  • Author(s): Iwatsuki-Horimoto et al.
  • Journal Title: J.Virol. (印刷中)
• [Book] Curr Top Microbiol Immunol (2004)
  • Author(s): Neumann G, Kawaoka, Y.
  • Total Pages: 18
  • Publisher: Springer, London, UK
• [Publications] Horimoto T, Takada A, Iwatsuki-Horimoto K, Hatta M, Goto H, Kawaoka Y.: "Generation of Influenza A viruses with chimeric(type A/B)hemagglutinins."Journal of Virology. 77. 8031-8038 (2003)
• [Publications] Watanabe T, Watanabe S, Noda T, Fujii Y, Kawaoka Y.: "Exploitation of nucleic acid packaging signals to generate a novel influenza virus-based vector stably expressing two foreign genes."Journal of Virology. 77. 10575-10583 (2003)
• [Publications] Fujii Y, Goto H, Watanabe T, Yoshida T, Kawaoka Y: "Selective incorporation of influenza virus RNA sements into virion"Proc Natl Acad Sci USA. 100. 2002-2007 (2003)