1995 Fiscal Year Final Research Report Summary
Identification of Determinants for Tropism of Sendai virus
| Project/Area Number |
06670334
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | National Institute of Health |
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Principal Investigator |
TASHIRO Masato National Institute of Health Dept.Virol.Director, ウイルス第一部, 部長 (90111343)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Kenichirou National Institute of Health Dept.Virol.Senior Researcher, ウイルス第一部, 主任研究官 (30150189)
ITAMURA Shigeyuki National Institute of Health Dept.Virol.Senior Researcher, ウイルス第一部, 主任研究官 (60203080)
INOUE Naoki National Institute of Health Dept.Virol.Senior Researcher, ウイルス第一部, 主任研究官 (90183186)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Sendai virus / Tropism / Tryptase clara / Budding polarity / Mictotubules / M protein / Epithelial cells / Protein transport |
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| Research Abstract |
1.We isolated and characterrizes a novel serine-protease designated "Tryptase Clara" , present in and secreted from the Clara cells of rat bronchial epithelia.Tryptase Clara was revealed to activate Sendai virus progeny by proteolytic cleavage of the F protein in rat lungs, and thereby facilitate multiple cycles of viral replication and pneumopathology.
2.Budding polarity of Sendai virus at the bronchial epithlial cells, the primary target of infection, was shown to determine the organ tropism.Apical budding by wild-type virus is responsible for licalized infectionin the airways, whereas basolateral budding is required for systemic spread of progeny virus to distant organs resulting in a systemic infection.
3.In addition to proteolytic activation of the F protein, basolateral expression of viral glycoproteins is a prerequisite for inducing cell fusion.
4.A mutant Sendai virus, F1-R,which buds bipolarly in epithelial cells, was shown to disrupt microtubule network in infected cells, resulting in impaired cellular polarity.By comparative analysis of the entire nucleotide sequence of wild type and F1-R viruses, the mutated M protein was identified to be responsible for this phenomenon.
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