Therapy for the chronic viral infection by activating the immune system

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790961
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Infectious disease medicine
• Research Institution: 財団法人東京都医学総合研究所 (2011); Tokyo Metropolitan Organization for Medical Research (2010)
• Principal Investigator: HIRATA Yuichi 財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (50439452)
• Project Period (FY): 2010 – 2011
• Keywords: 治療ワクチン / B型肝炎ウイルス

Research Abstract

We demonstrated that galactosylceramide, the activator of NKT cells, has an antiviral effect in HBV-Tg mice established as the experimental model for the chronic HBV infection. We also showed that polyIC with hepatotropic properties activates innate immune response, resulting in antiviral effect in HBV-infected chimeric mice with human livers. These results suggest the possibility that activation of innate immune response leads to the novel therapeutic approaches against the chronic HBV infection.
Further, we found that chronic HBV infection suppresses humoral factors from livers which are essential for maintaining immune cells by gene expression analysis using the next generation sequencer. This suppression of humoral factors caused the apoptosis of immune cells in livers. This result suggests the new mechanism of the chronicity of HBV infection, which leads to invent the new therapy.

Research Products

• [Journal Article] An orally available, small-molecule interferon inhibits viral replication (2012)
  • Author(s): Konishi H., Okamoto K., Ohmori Y., Yoshino H., Ohmori H., Ashihara M., Hirata Y., Ohta A., Sakamoto H., Hada N., Katsume A, Kohara M., Morikawa K., Tsukuda T., Shimma N., Foster GR., Alazawi W., Aoki Y., Arisawa M., Sudoh M
  • Journal Title: Sci Rep. Volume: 2 Pages: 259
  • Peer Reviewed
• [Journal Article] ヒト肝細胞での自然免疫応答におけるinterferon-λの重要性 (2011)
  • Author(s): 平田雄一、小原道法
  • Journal Title: 肝胆膵 Volume: 63 Pages: 1087-1094
• [Journal Article] Monoclonal antibody 2-152a suppresses hepatitis C virus infection through betaine/GABA transporter-1 (2011)
  • Author(s): Satoh M, Saito M, Takano T, Kasama Y, Nishimura T, Nishito Y, Hirata Y, Arai M, Sudoh M, Kai C, Kohara M, Tsukiyama-Kohara K
  • Journal Title: J Infect Dis. Volume: 204(8) Pages: 1172-80
  • Peer Reviewed
• [Journal Article] Augmentation of DHCR24 expression by hepatitis C virus infection facilitates viral replication in hepatocytes (2011)
  • Author(s): Takano T., Tsukiyama-Kohara K., Hayashi M., Hirata Y., Satoh M., Tateno C., Hayashi Y., Hishima T., Funata N., Sudo M., Kohara M.
  • Journal Title: J. Hepatology Volume: 55 Pages: 512-521
  • Peer Reviewed
• [Journal Article] Sphingomyelin activates hepatitis C virus RNA polymerease in a genotype specific manner (2010)
  • Author(s): Weng L., Hirata Y., Arai M., Kohara M., Wakita T., Watashi K., Shimotohno K., He Y., Zhong J., Toyoda T.
  • Journal Title: J Virol. Volume: 84(22) Pages: 11761-70
  • Peer Reviewed
• [Journal Article] スフィンゴ脂質合成阻害薬のC型肝炎ウイルスに対する薬理作用 (2010)
  • Author(s): 平田雄一、小原道法
  • Journal Title: 肝胆膵 Volume: 61 Pages: 216-222
• [Presentation] Suppression of sphingomyelin augmented by hepatitis C virus has robust anti-viral effects in human livers (2011)
  • Author(s): Hirata Y., Ikeda K., Sudoh M., Tokunaga Y., Tobita Y., Taguchi R., Kohara M
  • Organizer: The 62th Annual Meeting of the American Association for the Study of the Liver Disease
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20111104-08
• [Presentation] ヒト肝細胞での自然免疫応答におけるIFN-λの重要性とその誘導メカニズム (2011)
  • Author(s): 平田雄一、井上和明、小原道法
  • Organizer: 第19回消化器病学会関連週間(JDDW2011)
  • Place of Presentation: 福岡
  • Year and Date: 20111020-23
• [Presentation] Suppression of sphingomyelin augmented by hepatitis C virus has robust anti-viral effects in human livers (2011)
  • Author(s): Hirata Y., Ikeda K., Sudoh M., Tokunaga Y., Tobita Y., Taguchi R., Kohara M.
  • Organizer: International Union of Microbiological Societies 2011 Congress
  • Place of Presentation: Sapporo, Japan
  • Year and Date: 20110911-16
• [Presentation] A Interferon lambda plays a critical role on antiviral response by hepatotropic inducer of innate immunity in human hepatocyte (2010)
  • Author(s): Hirata Y., Nakagawa S., Tokunaga Y., Tanaka Y., Mizokami M., Inoue K., Kohara M
  • Organizer: The 61th Annual Meeting of the American Association for the Study of the Liver Disease
  • Place of Presentation: Boston, USA
  • Year and Date: 20101029-1102
• [Presentation] スフィンゴ脂質合成阻害剤の抗HCV薬理作用 (2010)
  • Author(s): 平田雄一、須藤正幸、小原道法
  • Organizer: 第18回消化器病学会関連週間(JDDW2010)
  • Place of Presentation: 横浜
  • Year and Date: 20101013-16
• [Presentation] IFNλを強力に誘導する核酸/リポソーム製剤の同定とその抗HCV効果 (2010)
  • Author(s): 平田雄一、井上和明、小原道法
  • Organizer: 第18回消化器病学会関連週間(JDDW2010)
  • Place of Presentation: 横浜
  • Year and Date: 20101013-16
• [Presentation] A newly synthesized serine palmitoyltransferase inhibitor, NA808, has a robust antiviral effect to hepatitis C virus via hindering host-virus interactions (2010)
  • Author(s): Hirata Y., Sudoh M., Tokunaga Y., Tobita Y., and Kohara M.
  • Organizer: The 17th International Meeting on Hepatitis C virus and related viruses
  • Place of Presentation: Yokohama
  • Year and Date: 20100910-14
• [Presentation] Hepatitis C virus altered the sphingolipids metabolism for better environment on its replication (2010)
  • Author(s): Hirata Y., Ikeda K., Sudoh M., Tokunaga Y., Taguchi R., Kohara M.
  • Organizer: KEYSTONE SYMPOSIA Bioactive Lipids
  • Place of Presentation: Kyoto
  • Year and Date: 20100606-11
• [Remarks]
  • URL: http://wwwigakuken.or.jp