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Protection of mice by a protease-activation mutant of Sendai virus against the challenge with the wild type virulent virus.

Research Project

Project/Area Number 59440034
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Virology
Research InstitutionKobe University School of Medicine

Principal Investigator

HOMMA Morio  School of Medicine Kobe University, Professor, 医学部, 教授 (10004566)

Co-Investigator(Kenkyū-buntansha) HOTTA Hak  School of Medicine Kobe University, Research Associate, 医学部, 助手 (40116249)
MURAKAMI Isamu  School of Medicine Kobe University, Research Associate, 医学部, 助手 (60107951)
FUJITA Nobuya  School of Medicine Kobe University, Lecturer, 医学部, 講師 (30030844)
TAKEHARA Manabu  School of Medicine Kobe University, Associate Professor, 医学部, 助教授 (40030829)
Project Period (FY) 1984 – 1986
Project Status Completed (Fiscal Year 1986)
Budget Amount *help
¥26,500,000 (Direct Cost: ¥26,500,000)
Fiscal Year 1986: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1985: ¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 1984: ¥14,000,000 (Direct Cost: ¥14,000,000)
KeywordsSendai virus / Protease-activation mutant / Trypsin / Chymotrypsin / Cleavage site mutant / 開裂部位変位 / 生ワクチン / マウス感染防御 / 同居感染 / 遺伝子解析
Research Abstract

Sendai virus penetrates the cells by fusing the envelope with the cytoplasmic membranes. We found that F protein of the envelope was specifically cleaved into smaller glycoproteins, F1 adn F2, by trypsin or trypsin-like enzymes, through which a new hydrophobic amino acid sequence appeared at the N-terminus of F1. On the basis of the above findings, we looked for the mechanism of preferential pneumopathogenicity of Sendai virus in mice and found that a trypsin-like enzyme present in the bronchiolar epithelium was responsible for the cleavage of F protein and the virus thus activated could replicate in multi-steps, causing pneumonia. To prove that, we obtained a protease-activation mutant, TR, which was resistant to trypsin but activated by chymotrypsin, instead. The activated TR could replicate in the lung but only in a single step and did not cause pneumonia. However, the mice became resistant to the challenge with the wild type virus. The present study aimed to analyse the property of TR as well as the mechanism of its protection and to determine the eligibility of TR as a candidate of a new type of live vaccine.
The results obtained were as follows. 1. The property of TR. TR had an enhanced sensitivity to chymotrypsin compared to the wild type virus besides the resistance to trypsin, for both of which was responsible a point mutation at the cleavage site. 2. The mechanism of TR-induced protection. The protection of TR against the challenge with the virulent virus was far solid compared to the usual inactivated split vaccine. This was mainly based on the induction of the virus specific cytotoxic T lymphocytes. 3. Applicability of TR as a new type of live vaccine. The protection was observed among several lines of mice so far tested and could be strengthend by a booster injection. The virus did not spread from the infectors of TR to the contacts int he same cage.
In conculsion, TR is competent as a novel live vaccine of Sendai virus in mice.

Report

(3 results)
  • 1986 Annual Research Report   Final Research Report Summary
  • 1985 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Masato Tashiro: Journal of Virology. 53. 288-234 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 本間 守男: 感染・炎症.免疫. 15. 1-11 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Morio Homma: Asian Medical Journal. 28. 137-147 (1985)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Masae Itoh: Journal of General Virology. 68. 2939-2944 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yosushi Mochizuki: Journal of Virology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Masato Tashiro: Journal of Virology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] A. L. Notkins. M. A. B. Oldstone eds Morio Homma: "Ceavage site mutant as a potential vaccine ″Concepts in Viral pathogenesis II″" Springer-Verlag, 425 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Masato Tashiro: "Protection of mice from wild-type Sendai virus infection by a trypsin-resistant mutant, TR-2." Journal of Virology. 53. 228-234 (1983)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Morio Homma: "Pneumotropism of Sendai virus (HVJ) in mice in relation to activation of the progeny virus in the lung." Asian Medical Journal. 28. 137-147 (1985)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Masae Itoh: "Single amino acid substitution of Sendai virus at the cleavage site of the fusion protein confers trypsin resistance." Journal of General Virology. 68. 2939-2944 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Yasushi Mochizuki: "Pneumopathogenicity in mice of a Sendai virus mutant, TSrev-58, is accompanied by in vitro activation with trypsin." Journal of Virology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Masato Tashiro: "Cell-mediated immunity induced in mice after vaccination with a protease-activation mutant, TR-2, of Sendai virus" Journal of Virology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] Morio Homma: Springer-Verlag. Cleavage site mutant as a potential vaccine "Concepts in viral pathogenesis II" A. L. Notkins, M. A. B. Oldstone eds., 388-393 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1986 Final Research Report Summary
  • [Publications] 伊藤正恵: Journal of General Virology.

    • Related Report
      1986 Annual Research Report
  • [Publications] 本間守男 eds.(A.L.Notkins;M.B.A.Oldstone,): "Cleavage site mutant as a potential vaccine.In "Concepts in viral pathogenesis II"" Springer-Verlag,New York., 388-393 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Journal of Virology. 53-1. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] モダンメディア. 31-2. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] Asian Medical Journal. 28-3. (1985)

    • Related Report
      1985 Annual Research Report
  • [Publications] 感染・炎症・免疫. 15-1. (1985)

    • Related Report
      1985 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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