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Establishment of an HTLV-I infection model by using human CRM1-transgenic rats

Research Project

Project/Area Number 17590411
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

OHASHI Takashi  Hokkaido Univ., Institute for Genetic Medicine, Asso. Prof., 遺伝子病制御研究所, 助教授 (10282774)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsHTLV-I / Tax / ATL / CRM1 / transgenic rat / animal model / HTLV-I / Animal model
Research Abstract

Human T-cell leukemia virus type I (HTLV-I) has been known to cause adult T-cell leukemia (ATL) in infected individuals after a long incubation period, but the in vivo mechanism by which the virus causes the malignant transformation is largely unknown. In order to develop a suitable animal model for the investigation of HTLV-I-related leukemogenesis, in this study, we have examined in vivo proliferation of HTLV-I in rats carrying the human CRM1 (hCRM1) gene, which encodes a viral RNA transporter shown in vitro to be a species specific restriction factor between human and rat. The hCRM1-transgenic (Tg) rats were established from an F344/Slc rat. We have isolated several HTLY-1-infected T cell lines from Tg rats and found that production of Gag by T cells derived from Tg rats were significantly higher than that by wild type (Wt)-derived cells. We next assessed the proliferation of HTLV-I in Tg rats by inoculating HTLV-I-infected T cells. Analysis of plasma pl9 concentration in the infected rats over time did not show significant differences between Tg and Wt rats, although pl9 concentration in Tg rats tended to be higher in the first 4 weeks after infection. We also assessed the tissue distribution of HT LV-I provirus DNA at 1 week after intraperitoneal infection and found that the rate of the virus disseminated to thymus in Tg rats was significantly higher than that in Wt rats. However, we have not detected notable difference in HTLV-I proviral load between the two groups so far. Since we have observed significant enhancement of HTLV-I production in cells derived from Tg rats in vitro, the limited effects of hCRM1 observed in vivo study suggests that HT LV-I-specific immune responses may reduce the enhanced virus production in Tg rats.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (7 results)

All 2007 2006 2005

All Journal Article (7 results)

  • [Journal Article] Enhanced Replication of Human T-cell Leukemia Virus Type 1 in T Cells from Transgenic Rats Expressing Human CRM1 That Is Regulated in a Natural Manner.2007

    • Author(s)
      Takayanagi R., et al.
    • Journal Title

      Journal of Virology (In Press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Enhanced Replication of Human T-cell Leukemia Virus Type 1 in T Cells from Transgenic Rats Expressing Human CRM1 That Is Regulated in a Natural Manner.2007

    • Author(s)
      Takayanagi R., et al.
    • Journal Title

      J Virol. (In Press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Erythroblast Transformation by the Friend Spleen Focus-Forming Virus Is Associated With a Block in Epo-Induced STAT1 Phosphorylation and DNA Binding And Correlates With High Expression of the Hematopoietic Phosphatase SHP-1.2006

    • Author(s)
      Nishigaki K., et al.
    • Journal Title

      Journal of Virology 80

      Pages: 5678-5685

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Erythroblast Transformation by the Friend Spleen Focus-Forming Virus Is Associated With a Block in Epo-Induced STAT 1 Phosphorylation and DNA Binding And Correlates With High Expression of the Hematopoietic Phosphatase SHP-1.2006

    • Author(s)
      Nishigaki K., et al.
    • Journal Title

      J Viral. 80

      Pages: 5678-5685

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Tumor immunity against adult T-cell leukemia.2005

    • Author(s)
      Kannagi M., et al.
    • Journal Title

      Cancer Science 96

      Pages: 249-255

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Potential immunogenicity of adult T-cell leukemia cells in vivo.2005

    • Author(s)
      Kurihara K., et al.
    • Journal Title

      International Journal of Cancer 114

      Pages: 247-267

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Potential immunogenicity of adult T-cell leukemia cells in vivo.2005

    • Author(s)
      Kurihara K., et al.
    • Journal Title

      Int.J.Cancer 114

      Pages: 247-267

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2005-04-01   Modified: 2016-04-21  

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