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Medical use of protease inhibitors for virus infection

Research Project

Project/Area Number 09044314
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokushima

Principal Investigator

KIDO Hiroshi  Institute for Enzyme Research, University of Tokushima, Professor, 分子酵素学研究センター, 教授 (50144978)

Co-Investigator(Kenkyū-buntansha) BODE Wolfram  Max-planch-Institute fuy Biochemie, Professor, 生化学部, 教授
FRITZ Hans  Dept.of clinic.Biochem.Univ.of Munich, Professor, 臨床化学生化学部, 教授
YANO Mihiro  the Institute for Enzyme Research, Lecturer, 分子酵素学研究センター, 助手 (40304555)
TOWATARI Takao  the Institute for Enzyme Research, University of Tokushima, assistant Professor, 分子酵素学研究センター, 助教授 (60108876)
TASHIRO Mashato  Natl.Iust.of Iufectous Diseare Dept.of viral Disease, ウイルス第一部, 部長 (90111343)
井上 雅広  徳島大学, 分子酵素学研究センター, 助手 (00232562)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Keywordsinfluenza virus / processing / tryptase Clara / plasmin / miniplasmin / antileukoprotease / elastase / urokinase / プロテアーゼ / プロテアーゼインヒビター / 生体防御物質 / エラフィン / 抗ウイルス作用
Research Abstract

Tryptase Clara, a uypsin-likc protease localized exclusively in and secreted from Clara cells of the bronchial epithielium proteolytically activates the infectivity of influenia A virus. In this rcsearch project, we found that miniplasmin as well as tryptase Clara also activates infectivity of influenza virus in vitro. Miniptasmin is formed From plasminoge n after processing by urokinase and elastase. To identify the endogenous inhibitor(s) of tryptase Clara in airway as a defensive compounds, we examined human bronchial lavage fluid and found two inhibitors of this enzyme. One was a pulmonary surfactant and the other was antilcukoprotease inhibitor (ALP). Miniplasmin was inhibited by hurnan-inter-alpha-trypsin inhibitor and urinary trypsin inhibitor but not by ALP.In this reseach, the two host proteases, tryptase Clara and miniplasrmn. and their endogerious inhibitors illustrate the role of cellular factors in the regulationof influenza virus infection.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Yoshihito Beppu: "Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses" J.Biochem.121. 309-316 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Molecular basis of proteolytic activation of Sendai virus infection and the defensive compounds for infection" Biol. Chem.378. 255-263 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 木戸博: "ウイルス感染を抑制する細胞性プロテアーゼとプロテアーゼインヒビター(インフルエンザとエイズウイルスを中心として)" 蛋白質核酸酵素. 42(14). 2399-2407 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 木戸博: "インフルエンザをめぐるトピックス" Pharma Medica. 16(11). 91-99 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 木戸博: "インフルエンザウイルスとセンダイウイルス感染を抑制する細胞性プロテアーゼとプロテアーゼインヒビター" 化学療法の領域. 15(2). 42-51 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai viruses" Biopolymers. in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Protease inhibitors and a pulmonary surfactant in airway fluid are potential defensive compounds against infection by influenza A and Sendai viruses" Proteolysis and Protein Turnover (V.K.Hopsu Havu ed.) IOS Press, 10 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Human mucus protease inhibitor and its mutants prevent infection by influenza A and Sendai viruses" Medical Aspects of Proteases and Protease Inhibitors (N.Katunuma, H.Kido, H.Furitz and J.Travis, eds.) IOS Press, 10 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Cellular proteinases and viral infection. Influenza virus, Sendai virus and HIV-1" Proteases of Infectious Agents (B.M.Dunn ed.) Academic Press, 13 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshihito Beppu et al.: "Human Mucus Protease Inhibitor in Airway Fluids is a Potential Defensive Compound against Infection with Influenza A and Sendai Viruses" J.Biochem.121(2). 309-316 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido et al.: "Molecular Basis of Proteolytic Activation of Sendai Virus Infection and the Defensive Compounds for Infection" Biol.Chem.378. 255-263 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido: "Role of Cellular Proteases and Protease Inhibitor in Viral Infection(Japanese)" Protein, Nucleic Acid and Enzyme. 42(14). 2399-2407 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido et al.: "Protease Inhibitors and a Pulmonary Surfactant in Airway Fluid are Potential Defensive Compounds Against Infection by Influenza A and Sendai Viruses" Proteolysis and Protein Turnover(V.K.Hopsu Havu ed.)IOS Press. 545-554 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido et al.: "Human Mucus Protease Inhibitor and its Mutants Prevent Infection by Influenza A and Sendai Viruses" Medical Aspects of Proteases and Protease Inhibitors(N.Katunuma, H.Kido, H.Fritz and J.Travis, eds) IOS Press. 118-127 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido et al.: "Topics of Influenza Virus Infection(Japanese)" Pharma Medica. 16. 118-127 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido et al.: "Cellular Protease and Protease Inhibitors that Regulate Infection by Influenza Virus and Sendai Virus(Japanese)" Antibiiotics and Chemotherapy. 15. 42-51 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido et al.: "Human Mucus Protease Inhibitor and its Mutants are Novel Defensive Compounds against Infection with Influenza A and Sendai Viruese" Biopolymers. (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Kido et al.: "Cellular Proteinases and Viral Infection.Influenza Virus, Sendai Virus and HIV-1." Proteases of Infectious Agents(B.M.Dunn, ed.). 205-217 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshihito Beppu: "Human mucus protease inhibitor in airway fluids is a potential defensive compound against infection with influenza A and Sendai viruses" J.icohem.121. 309-316 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroshi Kido: "Molecular basis of proteolytic activation of Sendai virus infection and the defensive compounds for infection" Biol.Chem.378. 255-263 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 木戸 博: "ウイルス感染を抑制する細胞性プロテアーゼとプロテアーゼインヒビター(インフルエンザとエイズウイルスを中心として)" 蛋白質核酸酵素. 42(14). 2399-2407 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 木戸 博: "インフルエンザをめぐるトピックス" Pharma Medica. 16(11). 91-99 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 木戸 博: "インフルエンザウイルスとセンダイウイルス感染を抑制する細胞性プロテアーゼとプロテアーゼインヒビター" 化学療法の領域. 15(2). 42-51 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroshi Kido: "Human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai vituses" Biopolymers. (in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroshi Kido: "Protease inhibitors and a pulmonary surfactant in airway fluid are potential defensive compounds against infection by influenza A and Sendai viruses" Proteolysis and Protein Turnover(V.K.Hopsu Havu ed.)IOS press, 10 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hiroshi Kido: "Human mucus protease inhibitor and its mutants prevent infection by influenza A and Sendai viruses" Medical Aspects of Proteases and Protease Inhibitors(N.Katunuma,H.Kido,H.Furitz and J.Travis,eds.)IOS Press, 10 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kido, H.: "Protease Inhibitors and a Pulmonary Surfactant in Airway Fluid are Potential Defensive Compounds Against Infection by Influenza A and Sendai Viruses," Proteolysis and Protein Turnover. 535-554 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kido, H.: "Molecular Basis of Proteolytic Activation of Sendai Virus Infection and the Defensive Compounds for Infection," Biol.Chem.,. 378. 255-263 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Beppu, Y.: "Human Mucus Protease Inhibitor in Airway Fluids is a Potential Defensive Compound against Infection with Influenza A and Sendai Viruses," J.Biochem.121(2). 309-316 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tashiro, M.: "Inhibitory Effect of Pulmonary Surfactant on Sendai Virus Infection in Rat Lungs," Arch.Virol.141. 1571-1577 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kido, H.: "Cellular Proteases Involved in The Pathogenicity of Enveloped Animal Virus,Human Immunodeficiency Virus,Influenza Virus A and Sendai Virus," Advan.Enzyme Regul.36. 325-347 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kido, H.: "Proteaes of Infectious Agents" Academic Press (Ben M.Dunn ed.)(in press), (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kido, H.: "Medical Aspects of Proteases and Protease Inhibitors" IOS Press (N.Katunuma,H.Kido et al.eds.), 205 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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