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Study on Persistent infection of Borna Disease Virus in Brain

Research Project

Project/Area Number 15580279
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionRakuno (kuen University

Principal Investigator

HAGIWARA Katsuro  Rakuno Gakuon University, Veterinary Medicine, Associate Professor, 獣医学部, 助教授 (50295896)

Co-Investigator(Kenkyū-buntansha) ISHIHARA Chiaki  Rakuno Gakuen University, Veterinary Medicine, Professor, 獣医学部, 教授 (90082172)
TANIYANMA Hiroyuki  Rakuno Gakuen University, Veterinary Medicine, Professor, 獣医学部, 教授 (90133800)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsBDV / PML / aponptosis / Caspase 3 / Bax / 持続感染 / PML蛋白質 / IFN
Research Abstract

The interferon (IFN)-induced proznyelocytic leukemia (PML) protein is associated with nuclear bodies (NBs) whose functions remain poorly understood. Overexpression of PML has been shown to affect the replication of several RNA viruses, including influenza and the complex retrovirus human foamy virus (HFV). Various viruses induce disorganization of the PML NBs, which is thought to be part of a general viral strategy to counteract IFN action. The mononegavirus Boron disease virus (BDV) can persistently infect neurons and astrocytes in the rat central nervous system (CNS) in the presence of a robust IFN response. Replication and transcription of BDV occur in the nucleus, a unique feature among known animal mononegaviruses. BDV antigens colocalize with PML, and persistence of BDV induces PML NBs disorganization suggesting a possible mechanism whereby BDV counteract the IFN response. Vero cells do not produce IFN, hence facilitating the evaluation of PML antiviral activity in the absence of … More other IFNinduced genes. Overexpression of PML via a recombinant adenovirus (AdPML) induced high levels of PML NBs structures in Vero cells, but did not exert any antiviiral activity against BDV Virus titers, as well as levels of BDV replication and transcription were similar in Vero cells that were infected with AdPML or mock-infected prior infection with BDV. In contrast, and consistent with a previous report, infection with AdPML resulted in about 1000-fold decrease in the production of infectious VSV. NBs have been implicated in hormone signaling, and glucocorticoids are potent modulators of astrocyte function. The resistance of BDV to the antiviral action of PML together with BDV mediated disorganization of PML NBs may contribute to disturbances in CNS function associated with BDV persistence.
PML is required for p53 pro-apoptotic signaling, as well as growth arrest inducing pathways. BDV persistence provides increased resistance to program cell death following exposure to Camptothecin. This effect was associated with impaired expression of the pro-apoptotic genes Caspase 3 and Bax. Protection from apoptosis was also observed in cells transfected with BDV N, Together these findings suggest that BDV N might be a repressor of apoptosis, an activity that could contribute to the exquisite ability of BDV to persist in brain cells. Less

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (14 results)

All 2005 2004 2003 Other

All Journal Article (12 results) Publications (2 results)

  • [Journal Article] The role of IFN-γ in cattle infected with theirelia sergenti2005

    • Author(s)
      Hagiwara K, Tokuda M, Baba T, et al.
    • Journal Title

      Vet.Parasitology 127(2)

      Pages: 105-110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of IFN-γ in cattle infected with Theirelia sergenti.2005

    • Author(s)
      Hagiwara K, Tokuda M, Baba T, Yamanaka H, Kirisawa R, Tsuji M, Ishihara C, Iwai H
    • Journal Title

      Vet.Parasitol. 127

      Pages: 105-110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of IFN-γ in cattle infected with Theirelia sergenti2005

    • Author(s)
      Hagiwara K, Tokuda M, Baba T.et al.
    • Journal Title

      Vet.Parasitology 127(2)

      Pages: 105-110

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Epizootiologic survey for Babesia microti among small wild mammals in northeastern Eurasia and ageographic diversity in the beta-tubulin gene sequences.2004

    • Author(s)
      Zamoto A, Tsuji M, Wei Q, Cho SH, Shin EH, Kim TS, Leonova GN, Hagiwara K, et al.
    • Journal Title

      J Vet Med Sci. 66(7)

      Pages: 785-792

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in interleukin-6 concentration in peripheral blood of pre-and past-partum dairy cattle and its relationship to postpartum reproductive diseases.2004

    • Author(s)
      Ishikawa Y, Nakada K, Hagiwara K, et al.
    • Journal Title

      J Vet Med Sci. 66(11)

      Pages: 1403-1408

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Changes in interleukin-6 concentration in peripheral blood of pre- and post-partum dairy cattle and its relationship to postpartum reproductive diseases.2004

    • Author(s)
      Ishikawa Y, Nakada K, Hagiwara K, Kirisawa R, Iwai H, Moriyoshi M, Sawamukai Y
    • Journal Title

      J Vet Med Sci.Nov 66(11)

      Pages: 1403-1408

    • NAID

      10014110049

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Epizootiologic survey for Babesia microti among small wild mammals in northeastern Eurasia and a geographic diversity in the beta-tubulin gene sequences.2004

    • Author(s)
      Zamoto A, Tsuji M, Wei Q, Cho SH, Shin EH, Kim TS, Leonova GN, Hagiwara K et al.
    • Journal Title

      J Vet Med Sci. 66(7)

      Pages: 785-792

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Changes in interleukin-6 concentration in peripheral blood of pre- and post-partum dairy cattle and its relationship to postpartum reproductive diseases.2004

    • Author(s)
      Ishikawa Y, Nakada K, Hagiwara K.et al.
    • Journal Title

      J Vet Med Sci. 66(11)

      Pages: 1403-1408

    • NAID

      10014110049

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Proinflammatory cytokines in bovine colostrum potentiate the mitogenic response of peripheral blood mononuclear cells from newborn calves through IL-2 and CD25 expression.2003

    • Author(s)
      Yamanaka H., Hagiwara K., Kirisawa R, Iwai H.
    • Journal Title

      Microbiol.Immunol. 47

      Pages: 461-468

    • NAID

      50000856330

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Experimental vertical transmission of Borna disease virus in the mouse.2003

    • Author(s)
      Okamoto M, Hagiwara K, Kamitani W, Sako T, Hirayama K, Kirisawa R, Tsuji M, Ishihara C, Iwai H, Kobayashi T, Tomonaga K, Ikuta K, Taniyama H
    • Journal Title

      Arch Virol.Aug 148(8)

      Pages: 1557-1568

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Transient detection of proinflammatory cytokines in sera of colostrum-fed newborn calves.2003

    • Author(s)
      Yamanaka H, Hagiwara K, Kirisawa R, Iwai H
    • Journal Title

      J Vet Med Sci.Jul 65(7)

      Pages: 813-816

    • NAID

      110003886264

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Proinflammatory cytokines in bovine colostrum potentiate the mitogenic response of peripheral blood mononuclear cells from newborn calves through IL-2 and CD25 expression.2003

    • Author(s)
      Yamanaka H., Hagiwara K, Kirisawa R, Iwai H
    • Journal Title

      Microbiol.Immunol. 47

      Pages: 461-468

    • NAID

      50000856330

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Okamoto M, Hagiwara K.et al.: "Experimental vertical transmission of Borna disease virus in the mouse."Arch Virol.. 148. 1557-1568 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 萩原克郎: "脳に感染するウイルス -日本におけるボルナ病ウイルスについて-"酪農ジャーナル. 7. 33-35 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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