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Analysis for the IL28B SNPs and IFN sensitivity using HCV cell culture models

Research Project

Project/Area Number 23590544
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Virology
Research InstitutionKagoshima University (2014)
Okayama University (2011-2013)

Principal Investigator

MASANORI Ikeda  鹿児島大学, 医歯(薬)学総合研究科, 教授 (30315767)

Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsHCV / IL28B SNPs / HuH-7 / Li23 / IFN-α / IFN-λ / IL28B / インターフェロン / IL28B SNP / rs8099917 / rs12979860 / rs8113007 / C型肝炎ウイルス
Outline of Final Research Achievements

The current standard therapy for chronic hepatitis C is based on pegylated-interferon (PEG-IFN)/ribavirin (RBV). In 2011, HCV protease inhibitor entered the clinical stage. The new treatment with protease inhibitor is also based on a combination of PEG-IFN/RBV. In 2009, SNPs upstream from the IL28B gene has been reported as strong predictive host factors of the effect of PEG-IFN/RBV. However, the precise mechanism underlying this influence is unclear. Therefore, we examined the IL28B genotypes for human hepatocyte cell lines in order to develop a cell culture model. HCV permissive Li23 and HuH-7 cells are exhibited IFN-sensitive and -resistant IL28B SNPs, respectively. The sensitivities to IFN-α are not significantly different in HCV harboring Li23 and HuH-7 cells. However, IFN-λ exhibited 100 times higher inhibitory effect on HCV RNA replication in Li23 cells than in HuH-7 cells. These HCV cell culture systems are useful tools for the study of IL28B SNPs and HCV.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (31 results)

All 2014 2013 2012 2011 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 2 results) Presentation (13 results) Remarks (3 results)

  • [Journal Article] Genetic Characterization of Hepatitis C Virus in Long-Term RNA Replication Using Li23 Cell Culture Systems.2014

    • Author(s)
      Kato N, Sejima H, Ueda Y, Mori K, Satoh S, Dansako H, Ikeda M.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 3 Pages: e91156-e91156

    • DOI

      10.1371/journal.pone.0091156

    • NAID

      120005697276

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anti-HCV activity of the Chinese medicinal fungus Cordyceps militaris.2014

    • Author(s)
      Ueda Y, Mori K, Satoh S, Dansako H, Ikeda M, Kato N.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 447 Issue: 2 Pages: 341-5

    • DOI

      10.1016/j.bbrc.2014.03.150

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rab18 is required for viral assembly of hepatitis C virus through trafficking of the core protein to lipid droplets.2014

    • Author(s)
      Dansako H, Hiramoto H, Ikeda M, Wakita T, Kato N.
    • Journal Title

      Virology

      Volume: 462-463 Pages: 166-74

    • DOI

      10.1016/j.virol.2014.05.017

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Adenosine kinase is a key determinant for the anti-HCV activity of ribavirin2013

    • Author(s)
      Mori K, Hiraoka O, Ikeda M, Ariumi Y, Hiramoto A, Wataya Y, Kato N
    • Journal Title

      Hepatology

      Volume: 58 Issue: 4 Pages: 1236-44

    • DOI

      10.1002/hep.26421

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] PML tumor suppressor protein is required for HCV production2013

    • Author(s)
      Kuroki M, Ariumi y, Hi j i ka ta M, Ikeda M, Dansnko H, Wakita T, Shimotohno K, Kato N
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 430 Issue: 2 Pages: 592-597

    • DOI

      10.1016/j.bbrc.2012.11.108

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] New preclinical antimalarial drugs potently inhibit hepatitis C virus genotype 1b RNA replication2013

    • Author(s)
      Ueda Y, et al.
    • Journal Title

      PLoS ONE

      Volume: 8 Issue: 8 Pages: e72519-e72519

    • DOI

      10.1371/journal.pone.0072519

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a drug assay system with hepatitis C virus genome derived from a patientwith acute hepatitis C2012

    • Author(s)
      Mori Kyoko
    • Journal Title

      Virus Genes

      Volume: (in press) Issue: 3 Pages: 374-381

    • DOI

      10.1007/s11262-012-0712-2

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of hepatitis C virus production reporter assay systems using two different hepatoma cell lines.2012

    • Author(s)
      Takeda M, Ikeda M, Ariumi Y, Wakita T, Kato N
    • Journal Title

      J. Gen. Virol

      Volume: 93 Issue: 7 Pages: 1422-1431

    • DOI

      10.1099/vir.0.040725-0

    • NAID

      120006331941

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of both protease and helicase activities of hepatitis C virus NS3 by an ethyl acetate extract of marine sponge Amphimedon sp.2012

    • Author(s)
      Fujimoto Y
    • Journal Title

      PLoS One.

      Volume: 7 Issue: 11 Pages: 744-761

    • DOI

      10.1371/journal.pone.0048685

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Raloxifene inhibits hepatitis C virus infection and replication.2012

    • Author(s)
      Takeda M, Ikeda M, Mori K, Yano M, Ariumi Y, Dansako H, Wakita T, Kato N
    • Journal Title

      FEBS Open Bio

      Volume: 2 Issue: 1 Pages: 279-283

    • DOI

      10.1016/j.fob.2012.08.003

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of host genes showing differential expression profiles with cell-based long-term replication of hepatitis C virus RNA.2012

    • Author(s)
      Sejima H, Mori K, Ariumi Y, Ikeda M, Kato N
    • Journal Title

      Virus Res

      Volume: 167 Issue: 1 Pages: 74-85

    • DOI

      10.1016/j.virusres.2012.04.008

    • NAID

      120006331940

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of hepatitis C virus production reporter assay systems using two different hepatoma cell lines.2012

    • Author(s)
      Takeda M, Ikeda M, Ariumi Y, Wakita T, Kato N.
    • Journal Title

      J. Gen. Virol.

      Volume: in press

    • NAID

      120006331941

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Anti-ulcer agent teprenone inhibits hepatitis C virus replication: Potential treatment for hepatitis C.2011

    • Author(s)
      Ikeda M, Kawai Y, Mori K, Yano M, Abe K, Nishimura G, Dansako H, Ariumi Y, Wakita T, Yamamoto K, Kato N.
    • Journal Title

      Liver Int.

      Volume: 31 Pages: 871-880

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanism of action of ribavirin in a novel hepatitis C virus replication cell system.2011

    • Author(s)
      Mori K, Ikeda M, Ariumi Y, Dansako H, Wakita T, Kato N.
    • Journal Title

      Virus Res.

      Volume: 151 Pages: 61-70

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus hijacks P-body and stress granule components around lipid droplets.2011

    • Author(s)
      Ariumi Y, Kuroki M, Kushima Y, Osugi K, Hijikata M, Maki M, Ikeda M, Kato N.
    • Journal Title

      J. Virol.

      Volume: 85 Pages: 6882-6892

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Characterization of anti-HCV activity of N-251, a preclinical antimalarial drug, and its combination effect with DAA.2014

    • Author(s)
      Ueda Y, Kim HS, Dansako H, Satoh S, Ikeda M, Doi H, Wataya Y, Kato N.
    • Organizer
      21st international symposium on hepatitis C virus and related viruses
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2014-09-07 – 2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Analysis on Transcriptional Regulatory Mechanisms of Genes whose Expressions were Reduced during Long-term Intracellular HCV-RNA Replication.2014

    • Author(s)
      Sejima H, Satoh S, Dansako H, Ikeda M, Kato N.
    • Organizer
      21st international symposium on hepatitis C virus and related viruses
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2014-09-07 – 2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Human Hepatoma HuH-7 Cell Line-derived RSc cells Show Higher Viral Productivity in Response to Infection with HCV-JFH-1 than Huh7.5 Cells.2014

    • Author(s)
      Dansako H, Hiramoto H, Ikeda M, Wakita T, Kato N.
    • Organizer
      21st international symposium on hepatitis C virus and related viruses
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2014-09-07 – 2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨粗鬆症治療剤であるラロキシフェンの抗HCV活性機構について2013

    • Author(s)
      武田 緑、池田 正徳、森 京子、矢野 雅彦、有海 康雄、團迫 浩方、脇田 隆字、加藤 宣之
    • Organizer
      第49回日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Raloxifene inhibits hepatitis C virus infection and replication2013

    • Author(s)
      Takeda M, Ikeda M, Mori K, Yano M, Ariumi Y, Dansako H, Wakita T, Kato N
    • Organizer
      20th international symposium on hepatitis C virus and related viruses
    • Place of Presentation
      Melbourne (Australia)
    • Related Report
      2013 Research-status Report
  • [Presentation] Anti-HCV activity of Cordyceps militaris used as a chinese herbal medicine2013

    • Author(s)
      Ueda Y, Mori K, Satoh S, Dansako H, Ikeda M, Kato N
    • Organizer
      20th international symposium on hepatitis C virus and related viruses
    • Place of Presentation
      Melbourne (Australia)
    • Related Report
      2013 Research-status Report
  • [Presentation] 2種類の肝細胞株(HuH-7とLi23)を用いたJFH-1株HCV感染レポーターアッセイシステムの開発と   感染効率を規定する宿主因子の検討2012

    • Author(s)
      武田 緑、池田 正徳、有海 康雄、脇田 隆字、加藤 宣之
    • Organizer
      第60回日本ウイルス学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] Li23細胞を用いた新しいJFH-1株HCV感染レポーターアッセイ系の開発と感受性を規定する因子の検討2012

    • Author(s)
      武田 緑、池田 正徳、有海 康雄、脇田 隆字、加藤 宣之
    • Organizer
      第16回日本肝臓学会大会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Development of HCV reporter-assay systems using two hepatoma cell lines and analysis of   the factors determining sensitivity to HCV infection.2012

    • Author(s)
      Takeda M, Ikeda M, Airumi Y, Wakita T, Kato N
    • Organizer
      19th international symposium on hepatitis C virus and related viruses
    • Place of Presentation
      Venice, Italy
    • Related Report
      2012 Research-status Report
  • [Presentation] Geranylgeranyl transferase II is essential for HCV RNA replication.2011

    • Author(s)
      Ikeda M, Takeda M, Ariumi Y, Wakita T, Kato N.
    • Organizer
      18th international symposium on hepatitis C virus and related viruses
    • Place of Presentation
      Seattle, USA
    • Related Report
      2011 Research-status Report
  • [Presentation] Development of HCV JFH-1 reporter assay systems using different human hepatoma cell lines.2011

    • Author(s)
      Takeda M, Ikeda M, Ariumi Y, Waikita T, Kato N.
    • Organizer
      Meetings of the Three Divisions of the International Union of Microbiological Societies 2011
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2011 Research-status Report
  • [Presentation] メバロン酸経路を標的とした新しい抗HCV剤開発の基礎2011

    • Author(s)
      池田 正徳、武田 緑、加藤 宣之
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Presentation] 2種類のヒト肝細胞株を用いたHCV感染レポーターアッセイ系の開発2011

    • Author(s)
      武田 緑、池田 正徳、有海 康雄、脇田 隆字、加藤 宣之
    • Organizer
      第47回日本肝臓学会総会
    • Place of Presentation
      東京
    • Related Report
      2011 Research-status Report
  • [Remarks] 分子ウイルス感染研究分野

    • URL

      https://sites.google.com/site/bunshiuirusukansenkenkyubunya/home

    • Related Report
      2014 Annual Research Report
  • [Remarks] 腫瘍ウイルス学分野

    • URL

      http://www.okayama-u.ac.jp/user/med/dmb/index.html

    • Related Report
      2013 Research-status Report
  • [Remarks] 腫瘍ウイルス学分野

    • URL

      http://www.okayama-u.ac.jp/user/med/dmb/index.html

    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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