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

• Project/Area Number: 22590737
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hiroshima 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: ¥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)
• Keywords: C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.

Research Products

• [Journal Article] Impact of interleukin-28B genotype on in vitro and in vivo systems of hepatitis C virus replication (2012)
  • Author(s): Chayama K, Hayes CN, Imamura M
  • Journal Title: Hepatol Res Volume: 42(9) Pages: 841-53
  • Peer Reviewed
• [Journal Article] Genetics of IL28B and HCV-response to infection and treatment (2012)
  • Author(s): Hayes CN, Imamura M, Aikata H, Chayama K
  • Journal Title: Nat Rev Gastroenterol Hepatol Volume: 9(7) Pages: 406-17
  • Peer Reviewed
• [Journal Article] Impact of interleukin-28B genotype on in vitro and in vivo systems of hepatitis C virus replication (2012)
  • Author(s): Chayama K
  • Journal Title: Hepatol Res Volume: 42 Issue: 9 Pages: 841-53
  • DOI: 10.1111/j.1872-034x.2012.01002.x
  • Peer Reviewed
• [Journal Article] Genetics of IL28B and HCV-response to infection and treatment (2012)
  • Author(s): Hayes CN
  • Journal Title: Nat Rev Gastroenterol Hepato Volume: 9 Issue: 7 Pages: 406-17
  • DOI: 10.1038/nrgastro.2012.101
  • Peer Reviewed
• [Journal Article] Impact of viral amino acid substitutions and host IL28B polymorphism on replication and susceptibility to interferon of hepatitis C virus (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Inverse association of IL28B genotype and liver mRNA expression of genes promoting or suppressing antiviral state (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Rapidemergence of telaprevir resistanthepatitis C virus strain from wildtypeclone in vivo (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Elimination of Hepatitis C Virus by Short Term NS3-4A and NS5B Inhibitor Combination Therapy in Human Hepatocyte Chimeric Mice (2011)
  • 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
  • Peer Reviewed
• [Journal Article] ME3738 enhances the effect of interferon andinhibits hepatitis C virusreplication both in vitro and in vivo (2011)
  • 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
  • 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
  • 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
  • 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
  • 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
• [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
• [Presentation] Deep sequencing analysis of hepatitis C virus quasipiecies in patients treated with telaprevir in combination with peginterferon and ribavirin (2012)
  • Author(s): Michio Imamura
  • Organizer: The 10th JSH Single Topic Conference
  • Place of Presentation: Tokyo
• [Presentation] Impact of Viral Amino Acid Substitutions and Host IL28B polymorphism on Replication and Susceptibility to Interferon of Hepatitis C Virus (2011)
  • 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
• [Presentation] Impact of Viral Amino Acid Substitutions and Host IL28B polymorphism on Replication and Susceptibility to Interferon of Hepatitis C Virus (2011)
  • Author(s): Michio Imamura, et al
  • Organizer: 12th AASLD
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2011-11-04
• [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
• [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
• [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
• [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
• [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
  • Organizer: The 7th APASL Single Topic Conference
  • Place of Presentation: Makuhari, Japan
  • Year and Date: 2010-12-17
• [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
• [Presentation] IL-28B predicts response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b (2010)
  • 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
• [Presentation] IL-28B predicts response to peginterferon-alfa-2b plus ribavirin therapy in Japanese patients infected with hepatitis C virus genotype 1b (2010)
  • Author(s): Michio Imamura
  • Organizer: HCV 2010
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2010-09-13
• [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
• [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
• [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
• [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