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Theiler's virus as a vector for foreign gene delivery into the CNS

Research Project

Project/Area Number 09670675
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKanazawa Medical University

Principal Investigator

OHARA Yoshiro  Kanazawa Medical University, Department of Microbiology, Professor, 医学部, 教授 (50203914)

Co-Investigator(Kenkyū-buntansha) OBUCHI Masatsugu  Kanazawa Medical University, Department of Microbiology, Assistant Professor, 医学部, 助手 (70257450)
村山 次哉  金沢医科大学, 医学部, 助教授 (60159184)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsTheiler's virus / CNS / lymphotoxin gene / vector / macrophages
Research Abstract

We reported that DA strain of Theiler's murine encephalomyelitis virus (TMEV) grows in macrophages where persists in the chronic stage if infection, therefore maintaining the genome. On the other hand, GDVII strain of TMEV does not grow there, and cannot maintain the genome (J Virol 71 : 729-733, 1997). Such a strain-specific, host cell-dependent virus growth was observed only in macrophages, but not in other types of cells (Microbiol Immunol, 43 : 885-892, 1999). Recombinant and mutant virus study also demonstrated that LィイD1*ィエD1 protein, which is out-of-frame with the polyprotein and translated from the alternative AUG within the L coding region, plays an important role for this phenomenon (J Virol 72 : 4950-4955, 1998). We finally inserted lymphotoxin (LT) gene into the L coding region of DA strain of TMEV and generated the recombinant virus. Western blotting and enzyme-linked immunosorbent assay demonstrated the expression of LT in BHK-21 cells infected with the recombinant virus. In addition, the expressed LT showed cytotoxicity against L-929 cells. Therefore, the present study provides a beginning of the use of TMEV as a vector for foreign gene delivery into the CNS.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Obuchi M et al: "Theiler's murine encephalomyelitis virus subgroup strain-specific infection in a macrophage-like cell line"J Virol. 71. 729-733 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M, Ohara Y: "Theiler's murine encephalomyelitis virus and mechanisms of its persistence"Neuropathology. 18. 13-18 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takata et al: "L* protein of the DA strain of Theiler's murine encephalomyelitis is important for virus growth in a murine macrophage-like cell line"J Virol. 72. 4950-4955 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M et al: "Expression of lymphotoxin gene inserted into Theiler's murine encephalomyelitis virus"Microbiol Immunol. 43. 83-86 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M et al: "Theiler's murine encephalomyelitis virus (TMEV) subgroup strain-specific infection in neural and non-neural cell lines"Microbiol Immunol. 43. 885-892 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M, Ohara Y: "Theiler's murine encephalomyelitis virus (TMEV) : the role of a small out-of-frame protein in virus persistence and demyelination"Jap J Infec Dis. 52. 228-233 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 大原義朗(分担): "免疫学からみた神経系と神経疾患"日本医学館. 374 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M et al.: "Theiler's murine encephalomyelitis virus subgroup strain-specific infection in a macrophage-like cell line"J Virol. 71. 729-733 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M, Ohara Y.: "Theiler's murine encephalomyelitis virus and mechanisms of its persistence"Neuropathology. 18. 13-18 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takata et al.: "LィイD1*ィエD1 protein of the DA strain of Theiler's murine encephalomyelitis is important for virus growth in a murine macrophage-like cell line"J Virol. 72. 4950-4955 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M et al.: "Expression of lymphotoxin gene inserted into Theiler's murine encephalomyelitis virus"Microbiol Immunol. 43. 83-86 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M et al.: "Theiler's murine encephalomyelitis virus (TMEV) subgroup strain-specific infection in neural and non-neural cell lines"Microbiol Immunol. 43. 885-892 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M, Ohara Y.: "Theiler's murine encephalomyelitis virus (TMEV) : the role of a small out-of-frame protein in virus persistence and demyelination"Jap J Infec Dis. 52. 228-233 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Obuchi M et al: "Expression of lymphotoxin gene inserted into Theiler's murine encephalomyelitisi virus"Microbiol.Immunol.. 43. 83-86 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Obuchi M et al: "Theiler's murine encephalomyelitis virus(TMEV) subgroup strain-specific infection in neural and non-neural cell lines"Microbiol.Immunol.. 43. 885-892 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohara Y: "Multiple sclerosis and measls virus"Jap.J.Infec.Dis. 52. 198-200 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Obuchi M,Ohara Y: "Theiler's murine encephalomyelitis virus(TMEV):the role of a small out-of-frame protein in virus persistence and demyelination"Jap.J.Infec.Dis. 52. 228-233 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大原義朗: "Theilerウイルスー持続感染と脱髄の発症機序に関する一考察ー"ウイルス. 49. 175-181 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大原義朗: "ウイルス持続感染のメカニズム"医学のあゆみ. 189. 935-938 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 大原義朗(分担): "免疫学からみた神経系と神経疾患"日本医学館. 374 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takata et al: "L^* protein of the DA strain of TMEV is important for virus growth in a murine macrophage-like cell line" Journal of Virology. 72. 4950-4955 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obuchi M et al: "TMEV and its persistence" Neuropathology. 18. 13-18 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohara et al: "Arthropod-borne tularemia in Japan" Am.J.Entomol.35. 471-473 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大原義朗: "神経感染症の疾患治療薬の分類と臨床薬里" 今月の治療. 6. 83-87 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 吉田孝人他: "感染症の免疫学的機序" 日本医学館(印刷中), (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Obuchi M et al: "TMEV subgroup strain-specific infection in a murine macrophage cell line" Journal of Virology. 71. 729-733 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Murayama T et al: "HCMV induces IL-8 production by THP-1,through acting concurrently on AP-1-and NF-k-B-binding sites of the IL-8 gene" Journal of Virology. 71. 5692-5696 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大原義朗: "ウイルス感染後アレルギー性神経疾患" 日本臨床. 55. 800-804 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大原義朗: "ウイルスと持続感染" Neuro・Infection. 1. 23-36 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 杉田秀夫: "HIV感染による神経障害の診療マニュアル" 新興医学出版社, 237 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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