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The study of virus-induced brain disorders by a model system using neural stem cells

Research Project

Project/Area Number 13670210
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

KOSUGI Isao  Hamamatsu University School of Medicine, Research Associate, 医学部, 助手 (10252173)

Co-Investigator(Kenkyū-buntansha) TSUTSUI Yoshihiro  Hamamatsu University School of Medicine, Professor, 医学部, 教授 (50073135)
TSUCHIDA takashi  Hamamatsu University School of Medicine, Research Associate, 医学部, 助手 (30317755)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsneural stem cells / virus / cytomegalovirus / brain disorders / virus vector / gene transduction / サイトメガロウイルス
Research Abstract

Cytomegalovirus (CMV) is the most frequent infectious cause of development disorders of the brain in humans. Infection of the neural stem/progenitor cells (NSPCs) seems to be primarily responsible for the generation of the brain abnormalities. Previously, we reported that NSPCs prepared from fetal mouse brains were permissive for murine CMV (MCMV) infection, and that the virus infection suppressed their growth and migration, and inhibited their differentiation, especially neuronal differentiation (Lab Invest 2000). However, it needs to be elucidated how viral genes cause the disorder of NSPCs during MCMV infection. In this study we tried to establish a model system for investigating the effects of MCMV genes on the growth and differentiation of NSPCs. An immediate early 1 (ie1) gene was transduced into NSPCs via a retrovirus vector. The transduction of ie1 suppressed the growth of NSPCs. When NSPCs were induced to differentiate, in the ie1-transduced NSPCs the expression of microtubules-associated protein 5 (MAP5), an early neuronal marker, was decreased as compared with control. These data suggest that MCMV IE1 protein disrupts the ability of self-renewal and multi-potency which are the principal functions of NSPCs. The transduction of viral genes into NSPCs might provide a model system for clarifying the pathogenesis of the brain abnormalities in congenital CMV infection in humans.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Arai Y, et al.: "Neuron-specific Activation of Murine Cytomegalobirus Early Gene el Promoter in Transgenic mice"American Journal of Pathology. (印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi I, IKawasaki H, Aral Y, Tsutsui Y.: "Innate Immune Reponses to Cytomegalovirus Infection in the Developing Mouse Brain and Their Evasion by Virus-Infected Neurons"American Journal of Pathology. 161. 919-928 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki H, Kosugi I, Arai Y, Tsutsui Y.: "The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection"Laboratory Investigation. 82. 1347-1358 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsui Y, Kawasaki H, Kosugi I: "Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures"Journal of Virology. 76. 7247-7254 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura M, et al.: "A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle"Current Biology. 11. 1512-1516 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li R-Y, et al.: "Activation of murine cytoznegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice"Glia. 35. 41-52 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arai Y, Ishiwata M, Baba S, Kawasaki H, Kosugi I, Li R-Y, Tsuchida T, Miura K, Tsutsui Y: "Neuron-specific Activation of Murine Cytomegalobirus Early Gene el Promoter in Transgenic mice"American Journal of Pathology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawasaki H, Kosugi I, Arai Y, Tsutsui Y: "The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection"Laboratory Investigation. 82(10). 1347-1358 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi I, Kawasaki H, Arai Y, Tsutsui Y: "Innate Immune Reponses to Cytomegalovirus infection in the Developing Mouse Brain and Their Evasion by Virus-Infected Neurons"American Journal of Pathology. 161(3). 919-928 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tsutsui Y, Kawasaki H, Kosugi I: "Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures"Journal of Virology. 76(14). 7247-7254 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamura M, Zhou XZ, Kishi S, Kosugi I, Tsutsui Y, Lu KP: "A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle"Current Biology. 11(19). 1512-1516 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Li R-Y, Baba S, Kosugi I, Arai Y, Kawasaki H, Sinmura Y, Sakakibara S, Okano H, Tsutsui Y: "Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice"Glia. 35. 41-52 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi I, Kawasaki H, Arai Y, Tsutsui Y: "Innate immune responses to cytomegalovirus infection in the developing mouse brain and their evasion by virus-infected neurons"The American Journal of Pathology. 161(3). 919-928 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawasaki H, Kosugi I, Arai Y, Tsutsui Y: "The amount of immature glial cells in organotypic brain slices determines the susceptibility to murine cytomegalovirus infection"Laboratory Investigation. 82(10). 1347-1358 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tsutsui Y, Kawasaki H, Kosugi I: "Reactivation of latent cytomegalovirus infection in mouse brain cells detected after transfer to brain slice cultures"Journal of Virology. 76(14). 7247-7254 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nakamura M, Zhou XZ, Kishi S, Kosugi I, Tsutsui Y, Lu KP: "A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle"Current Biology. 11(19). 1512-1516 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Li RY, Baba S, Kosugi I, Arai Y, Kawasaki H, Shinmura Y, Sakakibara SI, Okano H, Tsutsui Y: "Activation of murine cytomegalovirus immediate-early promoter in cerebral ventricular zone and glial progenitor cells in transgenic mice"Glia. 35(1). 41-52 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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