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Impact of viral amino acid substitutions and host IL28B polymorphism on replication and susceptibility to interferon of hepatitis C virus

Research Project

Project/Area Number 22590737
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

IMAMURA Michio  広島大学, 病院, 病院助教 (40403513)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsC型慢性肝炎 / インターフェロン / IL38B遺伝子多型 / HCV Core変異 / ISDR / ヒト肝細胞キメラマウス / IL28B
Research Abstract

Using human hepatocyte chimeric ice, we found that hepatitis C virus (HCV) replication levels and response to interferon (IFN) are affected by mutations in the ISDR, not by amino acid substitutions in HCV Core region. We also found that the effect of IFN was significantly greater, and intrahepatic expression levels of IFN-stimulated genes were significantly higher in mice with the favorable IL28B allele.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (29 results)

All 2012 2011 2010

All Journal Article (12 results) (of which Peer Reviewed: 12 results) Presentation (17 results)

  • [Journal Article] Impact of interleukin-28B genotype on in vitro and in vivo systems of hepatitis C virus replication2012

    • Author(s)
      Chayama K, Hayes CN, Imamura M
    • Journal Title

      Hepatol Res

      Volume: 42(9) Pages: 841-53

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Genetics of IL28B and HCV-response to infection and treatment2012

    • Author(s)
      Hayes CN, Imamura M, Aikata H, Chayama K
    • Journal Title

      Nat Rev Gastroenterol Hepatol

      Volume: 9(7) Pages: 406-17

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Impact of interleukin-28B genotype on in vitro and in vivo systems of hepatitis C virus replication2012

    • Author(s)
      Chayama K
    • Journal Title

      Hepatol Res

      Volume: 42 Issue: 9 Pages: 841-53

    • DOI

      10.1111/j.1872-034x.2012.01002.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetics of IL28B and HCV-response to infection and treatment2012

    • Author(s)
      Hayes CN
    • Journal Title

      Nat Rev Gastroenterol Hepato

      Volume: 9 Issue: 7 Pages: 406-17

    • DOI

      10.1038/nrgastro.2012.101

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of viral amino acid substitutions and host IL28B polymorphism on replication and susceptibility to interferon of hepatitis C virus2011

    • Author(s)
      Hiraga N, Abe H, Imamura M, Tsuge M, Takahashi S, Hayes CN, Ochi H, Tateno C, Yoshizato K, Nakamura Y, Kamatani N, Chayama K
    • Journal Title

      Hepatology

      Volume: 54(3) Pages: 764-771

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state2011

    • Author(s)
      Abe H, Hayes CN, Ochi H, Tsuge M, Miki D, Hiraga N, Imamura M, Takahashi S, Kubo M, Nakamura Y, Kamatani N, Chayama K
    • Journal Title

      J Med Virol

      Volume: 83(9) Pages: 1597-607

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Rapidemergence of telaprevir resistanthepatitis C virus strain from wildtypeclone in vivo2011

    • Author(s)
      Hiraga N, Imamura M, Abe H, Hayes CN, Kono T, Onishi M, Tsuge M, TakahashiS, Ochi H, Iwao E, Kamiya N, Yamada I, Tateno C, Yoshizato K, Matsui H, KanaiA, Inaba T, Tanaka S, Chayama K
    • Journal Title

      Hepatology

      Volume: 54 Issue: 3 Pages: 781-788

    • DOI

      10.1002/hep.24460

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elimination of Hepatitis C Virus by Short Term NS3-4A and NS5B Inhibitor Combination Therapy in Human Hepatocyte Chimeric Mice2011

    • Author(s)
      Ohara E, Hiraga N, Imamura M, et al
    • Journal Title

      Journal of Hepatology

      Volume: 54(5) Issue: 5 Pages: 872-878

    • DOI

      10.1016/j.jhep.2010.09.034

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ME3738 enhances the effect of interferon andinhibits hepatitis C virusreplication both in vitro and in vivo2011

    • Author(s)
      Abe H, Imamura M, Hiraga N, Tsuge M, Mitsui F, Kawaoka T, Takahashi S, OchiH, Maekawa T, Hayes CN, Tateno C, Yoshizato K, Murakami S, Yamashita N, Matsuhira T, Asai K, Chayama K
    • Journal Title

      J Hepatol

      Volume: 55 Issue: 1 Pages: 11-18

    • DOI

      10.1016/j.jhep.2010.10.017

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Predictive value of the IL28B polymorphism on the effect of interferon therapy in chronic hepatitis C patients with genotypes 2a and 2b.2011

    • Author(s)
      Kawaoka T, Hayes CN, Ohishi W, Ochi H Maekawa T, Abe H, Tsuge M, Mitsui F Hiraga N, Imamura M, Takahashi S, Kubo M, Tsunoda T, Nakamura Y, Kumada H, Chayama K.
    • Journal Title

      J Hepatol

      Volume: 54 Pages: 408-414

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HCV substitutions and IL28B polymorphisms on outcome of peg-interferon plus ribavirin combination therapy.2011

    • Author(s)
      Hayes CN, Kobayashi M, Akuta N, Suzuki F, Kumada H, Abe H, Miki D, Imamura M, Ochi H, Kamatani N, Nakamura Y, Chayama K.
    • Journal Title

      Gut

      Volume: 60 Pages: 261-267

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Common variation of IL28 affects gamma-GTP levels and inflammation of the liver in chronically infected hepatitis C virus patients.2010

    • Author(s)
      Abe H, Ochi H, Maekawa T, Hayes CN, Tsage M, Miki D, Mitsui F, Hiraga N, Imamura M, Takahashi S, Ohishi W, Arihiro K, Kubo M, Nakamura Y, Chayama K.
    • Journal Title

      J Hepatol

      Volume: 53 Pages: 439-443

    • NAID

      120002577227

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] C型肝炎ウイルスの感染およびIFN治療におけるIL28B遺伝子多型の影響2012

    • Author(s)
      今村道雄,阿部弘美,平賀伸彦,越智秀典,茶山一彰
    • Organizer
      第77回インターフェロンサイトカイン学会
    • Place of Presentation
      神戸
    • Year and Date
      2012-06-01
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] IL28B,ITPA遺伝子多型およびウイルス変異からみたC型肝炎の治療方針2012

    • Author(s)
      今村道雄
    • Organizer
      第48回日本肝臓学会総会
    • Place of Presentation
      金沢
    • Related Report
      2012 Annual Research Report
  • [Presentation] Deep sequencing analysis of hepatitis C virus quasipiecies in patients treated with telaprevir in combination with peginterferon and ribavirin2012

    • Author(s)
      Michio Imamura
    • Organizer
      The 10th JSH Single Topic Conference
    • Place of Presentation
      Tokyo
    • Related Report
      2012 Annual Research Report
  • [Presentation] Impact of Viral Amino Acid Substitutions and Host IL28B polymorphism on Replication and Susceptibility to Interferon of Hepatitis C Virus2011

    • Author(s)
      Michio Imamura, Hiromi Abe, Nobuhiko Hiraga, Masataka Tsuge, Shoicih Takahashi, C. Nelson Hayes, Hidenori Ochi, Chise Tateno, Katsutoshi Yoshizato, Kazauaki Chayama
    • Organizer
      The 62th Annual Meeting of the American Association for the Study of Liver Diseases.
    • Place of Presentation
      San Francisco
    • Year and Date
      2011-11-04
    • Related Report
      2012 Final Research Report
  • [Presentation] Impact of Viral Amino Acid Substitutions and Host IL28B polymorphism on Replication and Susceptibility to Interferon of Hepatitis C Virus2011

    • Author(s)
      Michio Imamura, et al
    • Organizer
      12th AASLD
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 宿主およびウイルス因子からみた1b高ウイルス量C型慢性肝炎に対する治療方針2011

    • Author(s)
      今村道雄
    • Organizer
      第15回日本肝臓病学会大会
    • Place of Presentation
      福岡
    • Year and Date
      2011-10-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] C型慢性肝炎に対するこれまでの成績からみた今後の治療方針2011

    • Author(s)
      今村道雄
    • Organizer
      第47回日本肝臓病学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-06-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] C型慢性肝炎に対するIFNの治療成績の変遷およびIFN製剤を使用しない新規治療法の可能性2011

    • Author(s)
      今村道雄
    • Organizer
      第97回日本消化器病学会総会
    • Place of Presentation
      東京
    • Year and Date
      2011-05-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] The influences of viral mutations on HCV infectivity, replication ability and the susceptibility to interferon in human hepatocyte chimeric mice.2010

    • Author(s)
      Michio Imamura, Nobuhiko Hiraga, Masataka Tsuge, Shoichi Takahashi, Hiromi Abe, C. Nelson Hayes, Hidenori Ochi and Kazuaki Chayama
    • Organizer
      The 7th APASL Single Topic Conference
    • Place of Presentation
      Chiba
    • Year and Date
      2010-12-17
    • Related Report
      2012 Final Research Report
  • [Presentation] The influences of viral mutations on HCV infectivity, replication ability and the susceptibility to interferon in human hepatocyte chimeric mice2010

    • Author(s)
      Michio Imamura
    • Organizer
      The 7th APASL Single Topic Conference
    • Place of Presentation
      Makuhari, Japan
    • Year and Date
      2010-12-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] HCV感染マウスを用いたNS3/4A protease阻害剤およびNS5B polymerase阻害剤併用療法の有用性の検討2010

    • Author(s)
      今村道雄
    • Organizer
      第14回日本肝臓病学会大会
    • Place of Presentation
      横浜
    • Year and Date
      2010-10-14
    • Related Report
      2010 Annual Research Report
  • [Presentation] IL-28B predicts response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b2010

    • Author(s)
      Michio Imamura, Hidenori Ochi, Hiromi Abe, Tomokazu Kawaoka, Yoshimasa Hashimoto, Shoichi Takahashi, C. Nelson Hayes, Kazuaki Chayama
    • Organizer
      HCV 2010
    • Place of Presentation
      Yokohama
    • Year and Date
      2010-09-13
    • Related Report
      2012 Final Research Report
  • [Presentation] IL-28B predicts response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b2010

    • Author(s)
      Michio Imamura
    • Organizer
      HCV 2010
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2010-09-13
    • Related Report
      2010 Annual Research Report
  • [Presentation] C型慢性肝炎患者におけるIL28B 多型とウイルス側および宿主側因子との関連2010

    • Author(s)
      今村道雄,越智秀典,茶山一彰
    • Organizer
      第46回日本肝臓学会総会
    • Place of Presentation
      山形
    • Year and Date
      2010-06-27
    • Related Report
      2012 Final Research Report
  • [Presentation] C型慢性肝炎患者におけるIL28B多型とウイルス側および宿主側因子との関連2010

    • Author(s)
      今村道雄
    • Organizer
      第47回日本肝臓病学会総会
    • Place of Presentation
      山形
    • Year and Date
      2010-06-27
    • Related Report
      2010 Annual Research Report
  • [Presentation] C型慢性肝炎に対するインターフェロン治療におけるIL28B 多型とCore領域変異の影響2010

    • Author(s)
      今村道雄,越智秀典,茶山一彰.
    • Organizer
      第96回日本消化器病学会総会
    • Place of Presentation
      新潟
    • Year and Date
      2010-04-23
    • Related Report
      2012 Final Research Report
  • [Presentation] C型慢性肝炎に対するインターフェロン治療におけるIL28B多型とCore領域変異の影響2010

    • Author(s)
      今村道雄
    • Organizer
      第96回日本消化器病学会総会
    • Place of Presentation
      新潟
    • Year and Date
      2010-04-23
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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