• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1999 Fiscal Year Final Research Report Summary

Development of multily attenuated Sendai virus vaccine by means of reverse genetics

Research Project

Project/Area Number 10680785
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionOsaka Prefectural Institute of Public Health

Principal Investigator

ITOH Masae  Osaka Prefectural Institute of Public Health, Virology Division, Senior Researcher, 公衆衛生部, 主任研究員 (10201328)

Co-Investigator(Kenkyū-buntansha) HOTTA Hak  Kobe University School of Medicine, Department of Microbiology, Professor, 医学部, 教授 (40116249)
中川 直子  大阪府立公衆衛生研究所, 公衆衛生部, 主任研究員 (10280835)
OKUNO Yoshinobu  Osaka Prefectural Institute of Public Health, Virology Division, Director, 公衆衛生部, ウイルス課長 (30112064)
Project Period (FY) 1998 – 1999
KeywordsSendai virus / pathogenicity / apoptosis / necrosis / interferon
Research Abstract

(1) Identification of Sendai virus genes which determine mouse pathogenicity.
Comparing an attenuated mutant virus (MVC11) with a highly pathogenic wild-type virus (M1), we showed the single point mutation from Phe to Ser at the 170th position of the C protein abolished the virulence of Sendai virus against mice. Involvement of the C protein in pathogenicity was confirmed by examining some recombinant viruses recovered by means of reverse genetics which were lacking one or two of the set of the C proteins (C', C, Y1 and Y2).
(2) Mechanism of attention of the c protein mutant.
1) Interferon sensitivity: When MVC11 was infected to interferon α/β receptor (IFNR)-knock-out mice (A129), mice exhibited only slight decrease of body weight. The result demonstrated that MVC11 was attenuated in A129 to the same degree as in ordinary mice possessing IFNR, suggesting that interferon sensitivity does not relate to attenuation of MVC11.
2) Effect of death of infected cells: Attenuated viruses with mutations in the C protein like MVC11 induced necrosis as well as apoptosis. Death of the infected cells caused interruption of progeny virus production afterwards, and resulted in attenuation of viral pathogenicity. On the other hand, pathogenic viruses like M1 did not demonstrate significant cytopathic effect and released progeny virus continuously for a long time after infection. In the presence of caspase inhibitor which suppressed apoptosis but not necrosis, MVC11-infected cells died rapidly. These results suggested that necrosis plays an important role in causing death to attenuated virus-infected cells.
(3) Growth of recombinant Sendai virus: Recombinant virus of Sendai virus obtained from cDNA of the attenuated laboratory strain (Z), the C gene of which was substituted by that of MVC11 did not grow efficiently. Based on this observation, we are trying to introduce mutations into the F and V genes of MVC11 with the aim to establish multiply attenuated virus.

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Itoh, Masae: "Increased induction of apoptosis by a Sendai virus mutant is associated with attenuation of mouse pathogenicity"Journal of Virology. 72(4). 2927-2934 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Latorre, Patrizia: "The various Sendai virus C proteins are not functionally equivalent, and exert both positive and negative effects on viral RNA accumulation during the course of infection"Journal of Virology. 72(7). 5984-5993 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤 正恵: "センダイウイルスのマウス病原性発現機構"ウイルス. 49(1). 53-60 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 伊藤 正恵: "センダイウイルスのマウス病原性に関わるタンパク質"バイオサイエンスとインダストリー. 58(1). 32-35 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakagawa, Naoko: "Rapid detection and identification of two lineages of influenza B strains with monoclonal antibodies"Journal of Virological Methods. 79. 113-120 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Handajani, Retno: "Prevalence of GB virus C/hepatitis G virus(GBV-C/HGV)infection among various populations in Surabaya, Indonesia, and identification of novel groups of sequence variants"J. Clin. Microbiol.. 38(2). 662-668 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishido,Satoshi: "Methods in Molecular Medicine"The Human Press,Inc.(印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Itoh, M., Hotta, H. and Homma, M.: "Increased induction of apoptosis by a Sendai virus mutant is associated with attenuation of mouse pathogenicity."J. Virol.. 72(4). 2927-2934 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Latorre, P., Cadd, T., Itoh, M., Curran, J. and Kolakofsky, D.: "The various Sendai virus C proteins are not functionally equivalent and exert both positive and negative effects on viral RNA accumulation during the course of infection."J. Virol.. 72(7). 5984-5993 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Itoh, M.: "Mechanism of attenuation of Sendai virus mutants carrying mutations in the C protein."Uirusu. 49(1) (in Japanese). 32-35

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2001-10-23  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi