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On the development of the system to screen new anti-HCV drugs

Research Project

Project/Area Number 13557024
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Virology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

SHIMOTOHNO Kunitada  Inst. Virus. Res., Kyoto Univ., Professor, ウイルス研究所, 教授 (10000259)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,900,000 (Direct Cost: ¥13,900,000)
Fiscal Year 2002: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2001: ¥9,300,000 (Direct Cost: ¥9,300,000)
Keywordshepatitis C virus / chronic hepatitis / HCV genome / replication / replicon / ゲノム / RT-PCR / リバビリン / 複製複合体
Research Abstract

Hepatitis C virus is a causative agent for the development of chronic hepatitis. Since the incidence of the development of hepatocellular carcinoma among the patients with chronic hepatitis is higher than those with uninfected individuals, HCV infection plays important roles on the development of the disease. Prevention of HCV infection as well as eradication of HCV from HCV carriers is the prominent ways to prevent the onset of the disease. However the lack of the system to culture HCV in an appropriate cell lines hampers the development of HCV vaccine and anti-HCV agents. We isolated the HCV genome from cells in which HCV proliferates poorly and used it to establish a cell line in which HCV genome self-replicates efficiently. Using these cells, we have analyzed the effect of interferon on HCV genome proliferation. We obtained the cell lines that acquired the character to show the resistance to interferon for HCV proliferation. Because that the molecular mechanisms of the interferon action to HCV proliferation is not demonstrated clearly yet, this system may help to clarify the precise mechanism of interferon for HCV proliferation. Moreover, we found that HCV replicating complex is localized on possibly membrane of endoplasmic reticulum and is protected by lipid structure. This information may also be applied to develop a new agent with anti-HCV function.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Noguchi T, et al.: "Effects of mutation in hepatitis C virus nonstructural protein 5A on interferon resistance mediated by inhibition of PKR kinase activity in mammalian cells"Microbiol Immunol. 45. 829-840 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Marusawa H, et al.: "Regulation of Fas-mediated apoptosis by NF-kappaB activity in human hepatocyte derived cell lines"Microbiol Immunol. 45. 483-489 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watashi K, et al.: "Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein through its amino terminal region"Virology. 286. 391-402 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okoshi S, et al.: "Molecular dissection of hepatitis C virus expression"Intervirology. 44. 21-28 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda K, et al.: "Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1,in response to mitogenic stimuli"Hepatology. 33. 159-165 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishine H., et al.: "Subgenomic replicon derived from a cell line infected with the hepatitis C virus"Biochem. Biophys. Res. Commun.. 293. 993-999 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimotohono K.: "Hepatitis C virus and its roles in cell proliferation"J. Gastroenterol. 37. 50-54 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Noguchi T, Satoh S, Noshi T, Hatada E, Fukuda R, Kawai A, Ikeda S, Hijikata M, Shimotohno K: "Effects of mutation in hepatitis C virus nonstructural protein 5A on interferon resistance mediated by inhibition of PKR kinase activity in mammalian cells"Microbiol Immunol. 45. 829-840 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Marusawa H, Hijikata M, Watashi K, Chiba T, Shimotohno K: "Regulation of Fas-mediated apoptosis by NF-kappa B activity in human hepatocyte derived cell lines"Microbiol Immunol. 45. 483-489 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watashi K, Hijikata M, Marusawa H, Doi T, Shimotohno K: "Cytoplasmic localization is important for transcription factor nuclear factor-kappa B activation by hepatitis C virus core protein through its amino terminal region"Virology. 286. 391-402 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okoshi S, Takeda Y, Takimoto M, Shimotohno K, Asakura H, Jay G: "Molecular dissection of hepatitis C virus expression"Intervirology. 44. 21-28 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukuda K, Tsuchihara K, Hijikata M, Nishiguchi S, Kuroki T, Shimotohno K: "Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli"Hepatology. 33. 159-165 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishine H., Sugiyama K., Hijikata M., Kato N., Takahashi H., Noshi T., Nio Y., Hosaka M., Miyanari Y., Shimotohno K: "Subgenomic replicon derived from a cell line infected with the hepatitis C virus"Biochem. Biophys. Res. Commun.. 293. 993-999 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimotohno K., Watashi K., Tsuchihara K., Marusawa H., Fukuda K., Hijikata M.: "Hepatitis C virus and its roles in cell proliferation"J. Gastroenterol.. 37. 50-54 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishine H, et al.: "Subgenomic replicon derived from a cell line infected with the hepatitis C virus. Biochem Biophys Res Commun"Biochem Biophys Res Commun. 293. 993-999 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueda Y, et al.: "Wnt/b-catenin signaling suppresses apoptosis in low serum medium and induces morphological change in rodent fibroblasts"Int.J.Cancer. 99. 681-688 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Masul O, et al.: "RelA suppresses the Wnt/beta-catenin pathway without exerting trans-acting transcriptional ability"Int.J.Mol.Med.. 9. 489-493 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimotohno K, et al.: "Hepatitis C virus and its roles in cell proliferation"J Gastroenterol.. 37. 50-57 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hwang J, et al.: "The RNA aptamer-binding site of hepatitis C virus NS3 protease"Biochem Biophys Res Commun. 279. 557-562 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hussein G, et al.: "Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease"Phytother Res. 14. 510-516 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Marusawa H, et al.: "Regulation of Fas-mediated apoptosis by NF-kappaB activity in human hepatocyte derived cell lines"Microbiol Immunol. 45. 483-489 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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