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Isolation of the cellular protease that determines infectious tropism of influenza virus in human and inhibition of the infection by the protease inhibitor from human bronchial lavage

Research Project

Project/Area Number 05557014
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionInstitute for Enzyme Research, The University of Tokushima

Principal Investigator

KIDO Hiroshi  Dept.of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Professor, 酵素科学研究センター, 教授 (50144978)

Co-Investigator(Kenkyū-buntansha) NINOMIYA Kenji  Product Development Laboratories, Tokyo Tanabe Co., Ltd., Research Head, 研究開発本部, 主任研究員
KAMOSHITA Keiichi  Research Laboratories Pharmaceuticals Group, Nippon Kayaku Co., Researcher, 総合研究所, 研究員
SUKENAGA Yoshikazu  Research Laboratories Pharmaceuticals Group, Nippon Kayaku Co., Research Head, 総合研究所, 主任研究員
TOWATARI Takae  Dept.of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokus, 酵素科学研究センター, 助教授 (60108876)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥18,900,000 (Direct Cost: ¥18,900,000)
Fiscal Year 1995: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1994: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1993: ¥9,000,000 (Direct Cost: ¥9,000,000)
Keywordsinfluenza virus / Tryptase Clara / pulmonary surfactant / anti-leucoprotease inhibitor / protease / protease inhibitor / defensive compounds / bronchial lavage / 肺サーファクタント / ヘムアクルチニン / 膜融合
Research Abstract

Tryptase Clara, a trypsin-like protease localized exclusively in and secreted from Clara cells of the bronchial epithelium proteolytically activates the infectivity of influenza A virus [H.Kido, Y.Yokogoshi, K.Sakai, M.Tashiro, Y.Kishino, A.Fukutomi and N.Katunuma (1992), J.Biol.Chem.267 : 13573-13579]. In this research project, we found two compounds in human bronchial ravage, which inhibited the proteolytic activation of influenza A virus by tryptase Clara in vitro and in vivo. One is pulmonary surfactant which specifically inhibited tryptase Clara with a Ki value of 1.3 * 10^<-7> M but not other trypsin-type proteases, such as trypsin, factor Xa, plasmin and mast cell trytase. The other compound in the lavage was a 12kDa protein which was identified to be a human mucus protease inhibitor (MPI) by the amino acid sequence analysis. MPI inhibited the activity of tryptase Clara, with a Ki value of 9.7 * 10^<-8> M and multicycles of mouse-adopted influenza A virus replication in rat lungs in vivo. MPI consists of two homologous domains and the C-terminal domain inhibited the virus activation but the N-terminal domain had little effect. Taken together, we found two endogenous local defensive compounds which inhibit proteolytic activation of influenza A virus by tryptase Clara. These compouds may be useful for the prevention and treatment of infection with influenza virus.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (62 results)

All Other

All Publications (62 results)

  • [Publications] H.Kido: "Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells : A possible activator of the viral fusion glycoprotein" J.Biol.Chem.267. 13573-13579 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Tashiro: "Tryptase Clara,an activating protease for Sendai virus in rat lungs,is involved in pneumopathogenicity" J.Virology. 66. 7211-7216 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sakai: "Electron immunohistochemical localization in rat bronciolar cells of tryptase Clara which determines the pneumotropium and pathogenicity of Sendai virus and influenza virus" J.Histochem.Cytochem.41. 89-93 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Pulmonary surfactant is a potential endogenous inhibitor of proteolytic activation of Sendai virus and influenza A virus" FEBS Lett.322. 115-119 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Tashiro: "Antibody against the carboxyl terminus of the F2 subunit of Sendai virus fusion glycoprotein inhibits proteolytic activation" Virology. 194. 882-885 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 木戸 博: "トリプターゼの生理機能" 組織培養. 19. 401-405 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 木戸 博: "ウイルス感染とプロテアーゼ-エイズウイルス,インフルエンザウイルスの感染と増殖に関与するプロテアーゼ-" 現代化学. 22. 214-221 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 木戸 博: "プロテアーゼインヒビター" 呼吸. 12. 1028-1035 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Sendai virus infection changes the subcellular localization of tryptase Clara in rat bronchiolar epithelial cells" Eur.Res.J.7. 686-692 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Iwata: "Assignment of disulfide bridges in the fusion glycoprotein of Sendai virus" J.Virology. 68. 3200-3206 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 木戸 博: "ウイルス感染と細胞内プロテアーゼ-インフルエンザウイルス、エイズウイルスを中心として-" 生化学. 66. 1130-1134 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 木戸 博: "インフルエンザの感染機序:気管支粘膜上皮細胞のプロテアーゼと制御因子" Medicine. 31. 1047-1049 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "トリプターゼクララとインフルエンザウイルス感染" The lung. 3. 74-78 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Cellular proteases involved in the pathogenicity of enveloped animal viruses,human immunodeficiency virus,influenza virus and Sendai virus" Advances in Enzyme Regulation. 34 (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Molecular basis of protease-mediated infection with Sendai virus and its endogenous defensive compounds" Biol.Chem.Hoppe-Seyler. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Proteolysis and Protein Turnover (J.S.Bond & A.J.Barrett,eds)" Portland Press,London, 18 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Intracellular Protein Catabolism (K.Suzuki & J.S.Bond,eds)" Plenum Publishing Corporation,New York (in press), (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Isolation and characterization of a novel trypsin-like protease found in rat bronchiolar epithelial Clara cells : possible activator of the viral fusion glycoprotein" J.Biol.Chem.267. 13573-13579 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Tashiro: "Tryptase Clara, an activating protease for Sendai virus in rat lungs, is involved in pneumo-pathogenicity" J.Virology. 66. 7211-7216 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] K.Sakai: "Electron immunohistochemical localization in rat bronchiolar epithelial cells of tryptase Clara which determines the pneumotropism and pathogenicity of Sendai virus and influenza virus" J.Histochem.Cytochem.41. 89-93 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Pulmonary surfactant is a potential endogenous inhibitor of proteolytic activation of Sendai virus and influenza A virus" FEBS Lett.322. 115-119 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] M.Tashiro: "Antibody against the carboxyl terminus of the F2 subunit of Sendai virus fusion glycoprotein inhibits proteolytic activation" Virology. 194. 882-885 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Biological functions of tryptase" Soshikibaiyo. 19. 882-885 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Role of proteases in viral infection : HIV and influenza virus" Gendai kagaku. 22. 214-221 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Protease inhibitor" Kokyu. 12. 1028-1035 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Cellular processing proteases for the envelope glycoprotein precursors of human immunodeficiency virus-1 and influenza and parainfluenza viruses, Proteolysis and Protein Turnover (J.S.Bond & A.J.Barrett, eds.)" Portland Press, London. 19. 209-217 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Sendai virus infection changes the subcellular localization of tryptase Clara in rat bronchiolar epithelial cells" Eur.Res.J.7. 686-692 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] S.Iwata: "Assignment of disulfide bridges in the fusion glycoprotein of Sendai virus" J.Virology. 68. 3200-3206 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Role of cellular proteases in viral infection : Influenza virus and HIV" Seikagaku. 66. 1130-1134 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Mechanisms of influenza virus infection : Proteases and their inhibitors secreted from bronchial epithelial cells" Molecular Medicine. 31. 1047-1049 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Role of tryptase Clara in influenza virus infection" The lung. 3. 74-78 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Cellular proteases involved in the pathogenicity of enveloped animal viruses, human immunodeficiency virus, influenza virus and Sendai virus" Advances in Enzyme Regulation. 34 (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Molecular basis of protease-mediated infection with Sendai virus and its endogenous defensive compounds" Biol.Chem.Hoppe-Seyler. (in press). (1966)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Cellular proteases involving pathogenicity of enveloped animal virus, human immunodeficiency virus and influenza virus, Intracellular Protein Catabolism (K.Suzuki & J.S.Bond, eds.)" Plenum Publishing Corporation New York. (in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] H.Kido: "Molecular basis of protease-mediated infection with Sencai virus and the endogenous defensive compounds" Biol.Chem.Hoppe-Seyler. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Kido: "Cellular proteases involved in the pathogenicity of enveloped animal virus,human immunodeficiency virus,influenza virus and Sendai virus" Advances in Enzyme Regulation. 36(in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 木戸 博: "トリプターゼクララとインフルエンザウイルス感染" The Lung. 3. 74-78 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] S.Iwata: "Assignment of disulfide bridges in the fusion glycoprotein of Sendai virus" J.Virology. 68. 3200-3206 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 木戸 博: "インフルエンザの感染機序:気管支粘膜上皮細胞のプロテアーゼと制御因子" Molecular Medicine. 31. 1047-1049 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Sakai: "Sendai virus infection changes the subcellular localization of tryptase Clara in rat bronchilar epithelial cells" Eur.Respir.J.7. 686-692 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Kido: "Mast Cell Proteases in Immunology and Biology" Cintrol of tryptase and chymase activity by protease inhibitors, 18 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] H.Kido: "Intracellular Protein Catabolism" Cellular proteases involving pathogenicity of enveloped animal virus,human immunodeficiency virus and influenza virus (in press), (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] K.Sakai: "Electron immunohistochemical localization in rat bronchiolar epithelial cells of tryptase Clara which determines the pneumo-tropism and pathogonicity of Sendai virus and influenza virus" J.Histochem.Cytochem.41. 89-93 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Kido: "Pulmonary surfactant is a potential endogenous inhibitor of proteolytic activation of Sendai virus and influenza A virus" FEBS Lett.322. 115-119 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.Tashiro: "Antibody against the carboxyl terminus of the F2 subunit of Sendai virus fusion glycoprotein inhibits proteolytic activatior" Virology. 194. 882-885 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Sukenaga: "Purification and molecular cloning of chymase from human tonsils" FEBS Lett.323. 119-122 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] K.Sakai: "Sendai visus infection changes the subcellular localization of tryptase Clara,an activating protease for pneumotropic viruses,in rat bronchiolar epithelial cells" Eur.Respir.J.7. 686-692 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] S.Iwata: "Assignment of disulfide bridges in the fusion glycoprotein of Sendai virus" J.Virology. 68. 3200-3206 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Kido: "Proteolysis and Protein Turnover" Portland Press,London, 9 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] H.Kido: "Intracellular Protein Catabolism" Plenum Publising Corporation,New York(in press), (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hiroshi Kido: "Pulmonary Surfactant is A Potential Endogenous Inhibitor of Proteolytic Activation of Sendai Virus and Influenza A Virus" FEBS Lett.322. 115-119 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kentaro Sakai: "Electron Immunohistochemical Localization in Rat Bronchiolar Epithelial Cells of Tryptase Clara which Determines The Pneumotropism and Pathogenicity of Sendai Virus and Influenza Virus" J.Histochem.Cytochem.41. 89-93 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masato Tashiro: "Antibody against The Carboxyl Terminus of THe F2 Subunit of Sendai Virus Fusion Glycoprotein Inhibit Proteolytic Activation" Virology. 194. 882-885 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Kentaro Sakai: "Sendai Virus Infection Changes the Subcellular Localization of Tryptase Clara,an Activating Protease for Pneumotropic Viruses,in Rat Bronchiolar Epithelial Cells" The European Respiratory Journal. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shoichi Iwata: "Assignment of Disulfide Bridges in the Fusion Glycoprotein of Sendai Virus" J.Virology. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Masato Tashiro: "Tryptase Clara,An Activating Protease for Sendai Virus in Rat Lungs,is Involved in Pneumopathogenicity" J.Virology. 66. 7211-7216 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] 木戸 博: "プロテアーゼインヒビター" 呼吸. 12. 1028-1035 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 木戸 博: "トリプターゼの生理機能" 組織培養. 19. 401-405 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 木戸 博: "ウイルス感染とプロテアーゼ-エイズウイルス,インフルエンザウイルスの感染と増殖に関するプロテアーゼ-" 現代化学. 22. 214-221 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 木戸 博: "ウイルス感染と細胞内プロテアーゼ-インフルエンザウイルス,エイズウイルスを中心として-" 生化学. (in press). (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hiroshi Kido: "Bological Functions of Proteases and Inhibitors" N.Katunuma,K.Suzuki,J.Travis and H.Holzer, 111-124 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hiroshi Kido: "Proteolysis and Protein Turnover" J.S.Bond and A.J.Barrett, 209-217 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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