| Project/Area Number |
10557033
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Virology
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| Research Institution | Institute for Enzyme Research, The University of Tokusahima |
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Principal Investigator |
KIDO Hiroshi Institute for Enzyme Research., The University of Tokushima, Professor, 分子酵素学研究センター, 教授 (50144978)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Masato National Institute of Infections Dieuse, Section Head, ウイルス製剤部, 部長 (90111343)
INOUE Masahoro Institute for Enzyme Research., The University of Tokushima, Assistant Professor, 分子酵素学研究センター, 助手 (00232562)
TOWATARI Takae Institute for Enzyme Research., The University of Tokushima, Associate Profesor, 分子酵素学研究センター, 助教授 (60108876)
YAMASHITA Makoto Sankyo Pharmaceutical Co., Researcher, 第二生物研究所, 研究員
BEPPU Yoshito Tokyotanabe Pharmaceutical Co., Researcher, プロジェクト推進室, 研究員
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2000: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1998: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | Influenza virus / Tryptase Clare / Trypsin / Sendai virus / Plasmin / Secretory protease / Airway / Alveolar / プロセシングプロテアーゼ / 分泌型プロデアーゼ |
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| Research Abstract |
Post-translational proteolytic cleavage of precursors of the envelope fusion glycoproteins of RNA viruses is indispensable for virus entry into host cells. It is widely known that the pathogenicity of mammalian and nonpathogenic avian influenza viruses, and Sendai virus is primarily determined by host cellular processing proteases in the respiratory tract, which proteolytically induce fusion of viral envelope glycoproteins, HA of influenza viruses, and F0 of Sendai virus with the plasma membrane of target cells, allowing the viral genome to enter the cytoplasm. In the period granted by this foundation, we found new members of protease in airway that, like tryptase Clara, can process influenza A virus hemagglutinin and Sendai virus envelope fusion glycoprotein. One was found in the epithelial cells of the upward divisions of bronchioles and identified to be a mini-plasmin. Mini-plasmin potentiated the replication of broad-spectrum influenza A viruses and Sendai virus, even that of the plasmin-insensitive influenza A virus strain. The other was found in the epithelial cells of alveolar of rat lungs and was identified to be an ectopic anionic pancreatic trypsin. Mucus protease inhibitor(MPI)in nasal liquids and bronchial lavage inhibited the activity of tryptase Clara and partly that of trypsin. Mini-plasmin was not inhibited by α1-antiplasmin and MPI.These findings indicate that there are several proteases potentiating the infectivity of influenza virus in different loci in airway and the infectivity of influenza virus is regulated by the balance between the amounts of these proteases and their inhibitors in airway.
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