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Analysis and Oa ntrol of HCV replication using HCV replicon system

Research Project

Project/Area Number 17390216
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionUniversity of Yamanashi

Principal Investigator

ENOMOTO Nobuyuki  University of Yamanashi, Department of Interdisciplinary, Graduate Schcol of Medicine and Engineering, Professor (20251530)

Co-Investigator(Kenkyū-buntansha) MAEKAWA Shinya  University of Yamanashi, Graduate School of Medical and Engineering, Research Associate (70397298)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥17,200,000 (Direct Cost: ¥15,700,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 2005: ¥5,700,000 (Direct Cost: ¥5,700,000)
KeywordsHCV / replicon / NS5A / lipid / innate immunity / C型肝炎ウイルス / スフィンゴ脂質 / インターフェロン / GFP
Research Abstract

The number of amino acid substitutions in the interferon sensitivity-determining region (ISDR) in the nonstructural 5A (NS5A) gene of hepatitis C virus (HCV) is closely associated with the interferon (IFN) response and viral load. Several HCV replicon-based studies have reported that ISDR sequences had an influence on viral replication in vitro. However, it is unclear as to how different ISDR sequences affect HCV replication. Various clinically observed ISDR sequences were introduced into HCV replicons and their contribution to viral replication was investigated using a colony formation assay and/or a transient replication assay. A mapping study of the ISDR was performed to identify the amino acid positions that critically affect replication. While no colonies were formed in the colony formation assay using HCV replicons with few mutations (0, 1 and 3) in the ISDR, numerous colonies (>200) appeared when using constructs with six mutations. Introduction of various distinct ISDR sequence … More s with multiple mutations resulted in replication enhancement in transient assays. A mapping study identified several specific sites in the ISDR that critically affected replication, including codon 2209 which, in patients, was closely associated with a strong response to IFN. ISDR sequences associated with a clinical IFN response and viral load modulated the replication of HCV replicons, suggesting the importance of the ISDR sequence in HCV infection.
The intracellular double-stranded (ds)RNA-mediated signal to induce type I interferon (IFN) plays a pivotal role in viral regulation. In hepatitis C virus (HCV), NS3/4A has been reported to block this system by cleaving IPS-1. However, an overall picture is still unclear, and it is unknown how different HCV strains affect this signal. Using three Huh7 cell lines (naive, replicon-harboring, and replicon-cured cells), poly I: C transfection-stimulated IRF-3 dimerization, and ISRE-promoter activation following overexpression of each signaling molecule were analyzed. Responsible HCV elements to block this signal were also investigated. To assess the role of HCV strain in the signal, the signal blocking capacities of HCV-N and HC-.J4 were compared. In contrast to naive and cured cells, IRF-3 dimerization was strongly suppressed in replicon-harboring cells, demonstrating HCV itself blocks the signal ISRE-promoter activation by RIG-I, and IPS-1 was remarkably suppressed in replicon-harboring cells, indicating RIG-I and/or IPS-1 were the main targets of HCV in this signal blockade. HCV-N-derived NS3/4A suppressed ISRE-promoter activation by RIG-I and IPS-I. HCV-N-derived NS4B also suppressed ISRE-promoter activation by IPS-I. On the other hand, HC-34-derived NS3/4A did not suppress ISRE-promoter activation by RIG-I and IPS-1. HCV replicon derived from HCV-N inhibits the dsRNA-mediated type I.
IFN induction signal through targeting RIG-I and/or IPS-1 by NS3/4A, and partly by NS4B. However, NS3/4A derived from HC-I4 could not significantly block the signal, indicating that the strain-specific blocking capacity might contribute to different replication capacity specific to each HCV replicon.
Recently, microdomains of organelle membranes rich in sphingomyelin and cholesterol (called "lipid rafts") have been considered to act as a scaffold for the hepatitis C virus(HCV) replication complex. Using the HCV cell culture system, we investigated the effect of myriocin, a sphingomyelin synthesis inhibitor, on HCV replication. We also investigated the combined effect of myriocin with interferon (IFN) and myriocin with simvastatin. Myriocin suppressed replication of both a genotype 1b subgenomic HCV replicon (Huh7/Rep-Feo) and genotype 2a infectious HCV(JFH-1 HCV) in a dose-dependent manner(for subgenomic HCV-1b, maximum of 79% at 1000nmol/L; for genomic HCV-2α, maximum of 40% at 1000 nmol/L). Combination treatment with myriocin and IFN or myriocin and simvastatin attenuated HCV RNA replication synergistically in Huh7/Rep-Feo cells. Our data demonstrate that the sphingomyelin synthesis inhibitor strongly suppresses replication of both the subgenomic HCV-1b replicon and the JFH-1 strain of genotype 2a infectious HCV, indicating that lipid metabolism could be a novel target for HCV therapy. Less

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (37 results)

All 2008 2007 2006 2005

All Journal Article (37 results) (of which Peer Reviewed: 18 results)

  • [Journal Article] Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity.2008

    • Author(s)
      Sekine-Osajima Y, Sakamoto N, Mishima K, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Kanai T, Tsuchiya K, Wakita T, Enomoto N, Watanabe M.
    • Journal Title

      Virology. 371

      Pages: 71-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Targeting lipid metabolism in the treatment of hepatitis C virus infection.2008

    • Author(s)
      Amemiya F, Maekawa S, Itakura Y, Kanayama A, Matsui A, Takano S, Yamaguchi T, Itakura J, Kitamura T, Inoue T, Sakamoto M, Yamauchi K, Okada S, Yamashita A, Sakamoto N, Itoh M, Enomoto N.
    • Journal Title

      J Infect Dis. 197

      Pages: 361-370

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Targeting lipid metabolism in the treatment of hepatitis C virus infection2008

    • Author(s)
      Amemiya, F., Maekawa, S., Itakura, Y., Kanayama, A., Matsui, A., Takano, S., Yamaguchi, T., Itakura, J., Kitamura, T., Inoue, T., Sakamoto, M., Yamauchi, K., Okada, S., Yamashita, A., Sakamoto, N., Itoh, M., Enomoto, N
    • Journal Title

      J Infect Dis 1 ; 197(3)

      Pages: 361-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Targeting lipid metabolism in the treatment of hepatitis C virus infection2008

    • Author(s)
      Amemiya F, Maekawa S, Itakura Y, Kanayama A, Matsui A, Takano S, Yamaguchi T, Itakura J, Kitamura T, Inoue T, Sakamoto M, Yamauchi K, Okada S, Yamashita A, Sakamoto N, Itoh M, Enomoto N
    • Journal Title

      J Infect Dis. 197

      Pages: 361-370

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity2008

    • Author(s)
      Sekine-Osajima Y, Sakamoto N, Mishima K, Nakagawa M, Itsui Y, Tasaka M, Nishimura-Sakurai Y, Chen CH, Kanai T, Tsuchiya K, Wakita T, Enomoto N, Watanabe M.
    • Journal Title

      Virology. 371

      Pages: 71-85

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response.2007

    • Author(s)
      Tasaka M, Sakamoto N, Itakura Y, Nakagawa M, Itsui Y, Sekine-Osajima Y, Nishimura-Sakurai Y, Chen CH, Yoneyama M, Fujita T, Wakita T, Maekawa S, Enomoto N, Watanabe M.
    • Journal Title

      J Gen Virol. 88

      Pages: 3323-3333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Inhibition of hepatitis C virus infection and expression in vitro and invivo by recombinant adenovirus expressing short hairpin RNA.2007

    • Author(s)
      Sakamoto N, Tanabe Y, Yokota T, Satoh K, Sekine-Osajima Y, Nakagawa M, Itsui Y, Tasaka M, Sakurai Y, Cheng-Hsin C, Yano M, Ohkoshi S, Aoyagi Y, Maekawa S, Enomoto N, Kohara M, Watanabe M.
    • Journal Title

      J Gastroenterol Hepatol. (Epub ahead of print)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity2007

    • Author(s)
      Sekine-Osajima, Y., Sakamoto, N., Mishima, K., Nakagawa, M., Itsui, Y., Tasaka, M.,Nishimura-Sakurai, Y., Chen CH, Kanai, T., Tsuchiya, K., Wakita, T., Enomoto, N., Watanabe, M
    • Journal Title

      Virology 5 ; 371(1)(Epub)

      Pages: 71-85

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response2007

    • Author(s)
      Tasaka, M., Sakamoto, N., Itakura, Y., Nakagawa, M., Itsui, Y., Sekine-Osajima, Y., Nishimura-Sakurai, Y., Chen CH, Yoneyama, M., Fujita, T., Wakita, T., Maekawa, S., Enomoto, N., Watanabe, M.
    • Journal Title

      J Gen Virol 88(Pt 12)

      Pages: 3323-33

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA2007

    • Author(s)
      Sakamoto, N., Tanabe, Y., Yokota, T., Satoh, K., Sekine-Osajima, Y., Nakagawa, M., ItsuiY, Tasaka, M., Sakurai, Y., Cheng-Hsin, C., Yano, M., Ohkoshi, S., Aoyagi, Y., Maekawa, S., Enomoto, N., Kohara, M., Watanabe, M
    • Journal Title

      J Gastroenterol Hepatol 7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response2007

    • Author(s)
      Tasaka M, Sakamoto N, Itakura Y, Nakagawa M, Itsui Y, Sekine-Osajima Y, Nishimura-Sakurai Y, Chen CH, Yoneyama M, Fujita T, Wakita T, Maekawa S, Enomoto N, Watanabe M
    • Journal Title

      J Gen Virol 88

      Pages: 3323-3333

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of hepatitis C virus infection and expression in vitro and in vivo byrecombinant adenovirus expressing short hairp RNA2007

    • Author(s)
      Sakamoto N, Tanabe Y, Yokota T, Satoh K, Sekine-Osajima Y, Nakagawa M, Itsui Y, Tasaka M, Sakurai Y, Cheng-Hsin C, Yano M, Ohkoshi S, Aoyagi Y, Maekawa S, Enomoto N, Kohara M, Watanabe M
    • Journal Title

      J Gastroenterol Hepatol (Epub ahead Of print)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication.2006

    • Author(s)
      Itsui Y, Sakamoto N, Kurosaki M, Kanazawa N, Tanabe Y, Koyama T, Takeda Y, Nakagawa M, Kakinuma S, Sekine Y, Maekawa S, Enomoto N, Watanabe M.
    • Journal Title

      J Viral Hepat. 13

      Pages: 690-700

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Site-specific mutation of the interferon sensitivity-determining region(ISDR)modulates hepatitis C virus replication.2006

    • Author(s)
      Kohashi T, Maekawa S, Sakamoto N, Kurosaki M, Watanabe H, Tanabe Y, Chen CH, Kanazawa N, Nakagawa M, Kakinuma S, Yamashiro T, Itsui Y, Koyama T, Enomoto N, Watanabe M.
    • Journal Title

      J Viral Hepat. 13

      Pages: 582-590

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 3.2006

    • Author(s)
      Yamashiro T, Sakamoto N, Kurosaki M, Kanazawa N, Tanabe Y, Nakagawa M, Chen CH, Itsui Y, Koyama T, Takeda Y, Maekawa S, Enomoto N, Sakugawa H, Watanabe M.
    • Journal Title

      J Gastroenterol. 41

      Pages: 750-757

    • NAID

      10018255879

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Analysis of prognostic factors in therapeutic responses to interferon in patients with chronic hepatitis C.2006

    • Author(s)
      Hosogaya S, Ozaki Y, Enomoto N, Akahane Y.
    • Journal Title

      Transl Res. 148

      Pages: 79-86

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Viral load change and sequential evolution of entire hepatitis C virus genome in Irish recipients of single source-contaminated anti-Dimmunoglobulin*.2006

    • Author(s)
      Itakura J, Nagayama K, Enomoto N, Hamano K, Sakamoto N, Fanning LJ, Kenny-Walsh E, Shanahan F, Watanabe M.
    • Journal Title

      J Viral Hepat. 12

      Pages: 594-603

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication2006

    • Author(s)
      Itsui, Y., Sakamoto, N., Kurosaki, M., Kanazawa, N., Tanabe, Y., Koyama, T., Takeda, Y., Nakagawa, M., Kakinuma, S., Sekine, Y., Maekawa, S., Enomoto, N., Watanabe, M
    • Journal Title

      J Viral Hepat 13(10)

      Pages: 690-700

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Site-specific mutation of the interferon sensitivity-determining region (ISDR modulates hepatitis C virus replication2006

    • Author(s)
      Kohashi, T., Maekawa, S., Sakamoto, N., Kurosaki, M., Watanabe, H., Tanabe, Y., Chen CH, Kanazawa, N., Nakagawa, M., Kakinuma, S., Yamashiro, T., Itsui, Y., Koyama, T., Enomoto, N., Watanabe, M
    • Journal Title

      J Viral Hepat 13(9)

      Pages: 582-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 32006

    • Author(s)
      Yamashiro, T., Sakamoto, N., KurOsaki, M., Kanazawa, N., Tanabe, Y., Nakagawa, M., Chen CH, Itsui, Y., Koyama, T., Takeda, Y., Maekawa, S., Enomoto, N., Sakugawa, H., Watanabe, M
    • Journal Title

      J Gastroenterol 41(8)

      Pages: 750-7

    • NAID

      10018255879

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Analysis of prognostic factors in therapeutic responses to interferon in patients with chronic hepatitis C2006

    • Author(s)
      Hosogaya, S., Ozaki, Y., Enomoto, N., Akahane, Y
    • Journal Title

      Transl Res 148(2)

      Pages: 79-86

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Site-specific mutation of the interferon sensitivity-determining region (ISDR) modulates hepatitis C virus replication.2006

    • Author(s)
      Kohashi T, Enomoto N, et al.
    • Journal Title

      J Viral Hepatitis 13

      Pages: 582-90

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor-3.2006

    • Author(s)
      Yamashiro T, Enomoto N, et al.
    • Journal Title

      J Gastroenterol 41

      Pages: 750-7

    • NAID

      10018255879

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication.2006

    • Author(s)
      Itsui Y, Enomoto N, et al.
    • Journal Title

      J Viral Hepatitis 13

      Pages: 690-700

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Site-specific mutation of the interferon sensitivity-determining region(ISDR) modulates hepatitis C virus replication.2006

    • Author(s)
      Kohashi T, Maekawa S, Sakamoto N, Watanabe H, Tanabe Y, Chen C-H, Nakagawa M, Kakinuma S, Enomoto N, Watanabe M.
    • Journal Title

      J Viral Hepatitis in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication.2006

    • Author(s)
      Itsui Y, Sakamoto N, Kurosaki M, Kanazaw N, Tanabe Y, Koyama T, Takeda Y, Nakagawa M, Kakinuma S, Sekine Y, Maekawa S, Enomoto N, Watanabe M
    • Journal Title

      J Viral Hepatitis in press

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Consensus proposals for a unified system of nomenclature of hepatitis Cvirus genotypes.2005

    • Author(s)
      Simmonds P, Bukh J, Combet C, Deleage G, Enomoto N, Feinstone S, Halfon P, Inchauspe G, Kuiken C, Maertens G, Mizokami M, Murphy DG, Okamoto H, Pawlotsky JM, Penin F, Sablon E, Shin-I T, Stuyver LJ, Thiel HJ, Viazov S, Weiner AJ, Widell A.
    • Journal Title

      Hepatology. 42

      Pages: 962-973

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C.2005

    • Author(s)
      Asahina Y, Izumi N, Enomoto N, Uchihara M, Kurosaki M, Onuki Y, Nishimura Y, Ueda K, Tsuchiya K, Nakanishi H, Kitamura T, Miyake S.
    • Journal Title

      J Hepatol. 43

      Pages: 623-629

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Suppression of hepatitis C virus replication by cyclosporin a is mediated by blockade of cyclophilins.2005

    • Author(s)
      Nakagawa M, Sakamoto N, Tanabe Y, Koyama T, Itsui Y, Takeda Y, Chen CH, Kakinuma S, Oooka S, Maekawa S, Enomoto N, Watanabe M.
    • Journal Title

      Gastroenterology. 129

      Pages: 1031-1041

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mutations in the NS5B region of the hepatitis C virus genome correlate with clinical outcomes of interferon-alpha plus ribavirin combination therapy.2005

    • Author(s)
      Hamano K, Sakamoto N, Enomoto N, Izumi N, Asahina Y, Kurosaki M, Ueda E, Tanabe Y, Maekawa S, Itakura J, Watanabe H, Kakinuma S, Watanabe M.
    • Journal Title

      J Gastroenterol Hepatol. 20

      Pages: 1401-1409

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Characteristic sequence changes of hepatitis C virus genotype 2b associated with sustained biochemical response to IFN therapy.2005

    • Author(s)
      Tanabe Y, Nagayama K, Enomoto N, Izumi N, Tazawa J, Kurosaki M, Sakamoto N, Sato C, Watanabe M.
    • Journal Title

      J Viral Hepat. 12

      Pages: 251-261

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Viral load change and sequential evolution of entire hepatitis C virus genoim in Irish recipients of single source-contaminated anti-D immunoglobulin*2005

    • Author(s)
      Italtura, J., Nagayama, K., Enomoto, N., Hamano, K., Sakamoto, N., Fanning, LJ., Kenny-Walsh, E., Shanahan, F., Watanabe, M
    • Journal Title

      J Viral Hepat 12(6)

      Pages: 594-603

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes2005

    • Author(s)
      Simmonds, P., Bukh, J., Combat, C., Deleage, G., Enomoto, N., Feinstone, S., Halfon, P., Inchauspe, G., Kuiken, C., Maertens, G., Mizokami, M., Murphy, DG., Okamoto, H., Pawlotsky, JM., Penin, F., Sablon, E., Shin-I,T., Stuyver, LJ., Thiel, HJ., Viazov, S., Weiner, AJ., Widen, A
    • Journal Title

      Hepatology 42(4)

      Pages: 962-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mutagenic effects of ribavirin and response to interferon/ribavirin combination therapy in chronic hepatitis C2005

    • Author(s)
      Asahina, Y., Izumi, N., Enomoto, N., Uchihara, M., Kurosaki, M., Onuki, Y., Nishimura, Y., Ueda, K., Tsuchiya, K., Nakanishi, H., Kitamura, T., Miyake, S
    • Journal Title

      J Hepatol 43(4)

      Pages: 623-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Suppression of hepatitis C virus replication by cyclosporin a is mediated by blockade of cyclophilins.2005

    • Author(s)
      Nakagawa, M., Sakamoto, N., Tanabe, Y., Koyama, T., Itsui, Y., Takeda, Y., Chen, CH., Kakinuma, S., Oooka, S., Maekawa, S., Enomoto, N., Watanabe, M
    • Journal Title

      Gastroenterology 129(3)

      Pages: 1031-41

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mutations in the NS5B region of the hepatitis C virus genome correlate with clinical outcomes of interferon-alpha plus ribavirin combination therapy2005

    • Author(s)
      Hamano, K., Sakamoto, N., Enomoto, N., Izumi, N., Asahina, Y., Kurosaki, M., Ueda, E., Tanabe, Y., Maekawa, S., Itakura, J., Watanabe, H., Kakinuma, S., Watanabe, M
    • Journal Title

      J Gastroenterol Hepatol 20(9)

      Pages: 1401-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Characteristic sequence changes of hepatitis C virus genotype 2b associated with sustained biochemical response to IFN therapy2005

    • Author(s)
      Tanabe, Y., Nagayama, K., Enomoto, N., Izumi, N., Tazawa, J., Kurosaki, M., Sakamoto, N., Sato, C., Watanabe, M
    • Journal Title

      J Viral Hepat 12(3)

      Pages: 251-61

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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