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Acquisition of Borna disease virus virulence by in vivo evolution

Research Project

Project/Area Number 08457091
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionHokkaido University

Principal Investigator

IKUTA Kazuyoshi  Institute of Immunological Science, Hokkaido University, Professor, 免疫科学研究所, 教授 (60127181)

Co-Investigator(Kenkyū-buntansha) IKEDA Kazuhiko  Tokyo Institute of Psychiatry, Head of Department, 精神医学総合研究所, 副参事研究員 (30124663)
中屋 隆明  北海道大学, 免疫科学研究所, 助手 (80271633)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1996: ¥3,900,000 (Direct Cost: ¥3,900,000)
KeywordsBorna disease virus / schizophrenia / Parkinson disease / autopsy brain / gerbil / hippocampus / cerebellum / substantia nigra / zoonosis / 病原性ウイルス / 好神経性ウイルス / うつ病 / 慢性疲労症候群 / 末梢血単核球
Research Abstract

Borna disease virus (BDV) is neurotropic envelope virus with nonsegmented, single-stranded and minus-stranded RNA as a genome. We have reported that BDV is distributed in Japanese animals such as horses, sheep, cattle and cats. Further, we have reported that BDV prevalence was significantly higher in patients with schizophrenia and chronic fatigue syndrome, compared with blood donors. In this study, we have worked on the possible identification of a virulent BDV in human brains and obtained results as follows :
1) We detected BDV RNA in hippocampus, pons and cerebellum in one among four autopsied brains derived from schizophrenia patients. In contrast, there are no positive cases in several brain regions examined which were derived from 2 autopsied healthy brains.
2) We isolated human BDV from BDV RNA-positive hippocampus and cerebellum by inoculation of these brain regions to newborn gerbils followed by co-culture of the gerbil brain with human oligodendroglioma-derived cell line. 3) Full-length nucleotide sequence of BDV derived from the brain of a patient with schizophrenia was determined and compared with that of horse brain-derived BDV.The homology of human BDV with horse BDV at nucleotide sequence level was about 98%. Especially, the phosphoprotein (p24) and glycoprotein (gp 56) had many ammo acid substitutions. 4) We have examined the possible detection of BDV RNA in substantia nigra from patients with Parkinson's disease. Three among four from A hospital and three among 5 from B hospital were positive for BDV RNA BDV RNA was also positive in newborn gerbils intracranially inoculated with these BDV RNA-positive substantia nigras. However, we could not detect BDV replication in human oligodendroglioma-derived cell line, although we examined under the same conditions as in BDV isolation from the brain of a patient with schizophrenia.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (64 results)

All Other

All Publications (64 results)

  • [Publications] Kobayashi, T., et al.: "Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein." Virology. 245. 53-64 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwahashi, K., et al.: "Positive and negative syndromes, and Borna disease virus(BDV) infection in schizophrenia." Neuropsychobiology. 37. 59-64 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoya, Y., et al.: "Two proline-rich nuclear localization signals in the amino- and carboxyl-terminal regions of Borna disease virus phosphoprotein" J.Virol.72. 9755-9762 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kohno, T., et al.: "Fine structure and morphogenesis of Borna disease virus(BDV)." J.Virol.in press. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 生田和良: "ボルナ病" 人と動物の共通感染症(丸山務、倉田毅、森田千春 編). 印刷中.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 中村百合恵、他: "ボルナ病ウイルス" 医学のあゆみ(新興再興感染症). 185・5. 345-348 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 高橋宏和他: "精神疾患との関連性がみられるボルナ病ウイルス" 臨床検査. 42・6. 694-695 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 庄谷 祐子、他: "ボルナ病ウイルス" 化学療法の領域. 32・1. 1-7 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 朝長 啓造他: "ヒトの神経を冒す新しいウイルス感染症-ボルナ病ウイルス感染症-" 遺伝. 53・2. 1-5 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 生田 和良: "新しいウイルス感染症-中枢神経系疾患と関連するボルナ病ウイルス-" LABEAM. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi, T., et al.: "Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein." Virology. 245. 53-64 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iwahashi, K., et al.: "Positive and negative syndromes, and Borna disease virus (BDV) infection in schizophrenia." Neuropsychobiology. 37. 59-64 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shoya, Y., et al.: "Two proline-rich nuclear localization signals in the amino- and carboxyl-terminal regions of Borna disease virus phosphoprotein." J.Virol.72. 9755-9762 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kohno, T., et al.: "Fine structure and morphogenesis of Borna disease virus (BDV)." J.Virol.73. 1,760-766 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi, T., et al.: "Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein." Virology. 245. 53-64 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwahashi, K., et al.: "Positive and negative syndromes, and Borna disease virus (BDV) infection in schizophrenia." Neuropsychobiology. 37. 59-64 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shoya, Y., et al.: "Two proline-rich nuclear localization signals in the amino- and carboxyl-terminal regions of Borna disease virus phosphoprotein" J.Virol.72. 9755-9762 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kohno, T., et al.: "Fine structure and morphogenesis of Borna disease virus(BDV)." J.Virol.in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 生田和良: "ボルナ病" 人と動物の共通感染症(丸山務、倉田毅、森田千春 編). (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] 中村百合恵、他: "ボルナ病ウイルス" 医学のあゆみ(新興再興感染症). 185・5. 345-348 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 高橋宏和他: "精神疾患との関連性がみられるボルナ病ウイルス" 臨床検査. 42・6. 694-695 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 庄谷 祐子、他: "ボルナ病ウイルス" 化学療法の領域. 32・1. 1-7 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 朝長 啓造他: "ヒトの神経を冒す新しいウイルス感染症 -ボルナ病ウイルス感染症-" 遺伝. 53・2. 1-5 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 生田 和良: "新しいウイルス感染症 -中枢神経系疾患と関連するボルナ病ウイルス-" LABEAM. (in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Hagiwara,K.: "High prevalence of Borna disease virus infection in healthy sheep in Japan." Ciln.Diagn.Lab.Immunol.4. 339-344 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fujiwara,S.: "Microplate hybridization for Borna disease virus RNA in human peripheral blood mononuclear cells." Ciln.Diagn.Lab.Immunol.4. 387-391 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takahashi,H.: "Higher prevalence of Borna disease virus infection in blood donors living near thoroughbred horse farms." J.Med.Virol.52. 330-335 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Shoya,Y.: "Amplification of a full-length Borna disease virus(BDV)cDNA from total RNA of cells persistently infected with BDV." Microbiol.Immunol.41. 481-486 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hagiwara,K.: "Demonstration of Borna disease virus(BDV)in specific regions of the brain from horses positive for serum antibodies to BDV but negative for BDV RNA in the blood and internal organs." Med.Microbiol.Immunol.186. 19-24 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwahashi,K.: "Clinical investigation of the relationship between Borna disease virus(BDV)infection and schizophrenia in 67 patients in Japan." Acta Psychiatr.Scand.96. 412-415 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Haga,S.: "Detection of Borna disease virus genome in normal human brain tissue." Brain Res.770. 307-309 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kobayashi,T.: "Nuclear targeting activity associated with the amino terminal region of the Borna disease virus nucleoprotein" Virology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Iwahashi,K.: "Positive and negative syndromes,and Borna disease virus(BDV)infection in schizophrenia." Neuropsychobiology. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 岩橋和彦他: "精神分裂病におけるボルナ病ウイルス(BDV)感染とPANSSを用いた精神分裂病症状評価" 臨床精神医学. 26. 261-266 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 岩橋和彦他: "ボルナ病ウイルス感染と精神分裂病" 精神医学. 39. 1275-1279 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 中村百合恵他: "ウマ、ウシ、ヒツジ、ネコおよびヒトにおけるボルナ病ウイルス感染状況" 獣医畜産新報 JVM. 50・3. 193-196 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病ウイルスの人への関与の可能性" ウイルス. 47・1. 37-47 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病ウイルス研究の最新動向" 医学のあゆみ. 181・8. 533-537 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病ウイルスと精神疾患" 日本医師会雑誌. 117・11. 1884- (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病" 小児内科「小児疾患診療のための病態生理」. 29. 914-916 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病ウイルス" BIO Clinica. 12・11. 60-64 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病ウイルス" 病原ウイルス学(加藤四郎、岸田綱太郎 編). 465-471 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病ウイルス -ヒト患者における疫学研究の現況-" 小児の臨床ウイルス学(浅野善造 編). 60・11. 53-59 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 中屋隆明他: "ボルナ病ウイルス(BDV)と慢性疲労症候群(CFS) -抗BDV抗体とBDV・RNAの検出-" 日本臨床「総説シリーズ -現代医学の焦点-」. 55・11. 264-271 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ヒトと動物におけるボルナ病ウイルス感染状況" 実験医学. 15・19. 219-223 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "北アメリカとヨーロッパの精神分裂病および双極障害患者の脳内に存在する" Medical Briefs in Herpes Virus Infection「ウイルス脳炎・脳症特集号」. 10・5. 8-9 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病" 人と動物の共通感染症(丸山努、倉田毅、森田千春 編). (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] 生田和良: "ボルナ病ウイルス" 医学のあゆみ(新興再興感染症). (印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] Kishi,M.: "Sequence variability of Borna disease virus open reading frame II found in human peripheral blood mononuclear cells." J. Virol.70・1. 635-640 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakaya, T.: "Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from Japanese patients with chronic fatigue syndrome." FEBS Lett.378. 145-149 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakamura, Y.: "Demonstration of Borna disease virus RNA in peripheral blood mononuclear cells derived from domestic cats in Japan." J. Clin. Microbiol.34・1. 188-191 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kitani, T.: "Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome." Microbiol. Immunol.40・6. 459-462 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Auwanit, W.: "Unusually high seroprevalence of Borna disease virus in clade E human immunodeficiency virus type 1-infected patients with sexually transmitted diseases in Thailand." Clin. Diagn. Lab. Immunol.3・5. 590-593 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Bahmani, M. K,: "Varied prevalence of Borna disease virus infection in Arabic, thoroughbred and their cross-bred horses in Iran." Virus Research. 45. 1-13 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nakaya, T.: "Expression of Borna disease virus messages in clinical samples from patients with brain malignant tumors." Proc. Japan Acad.72. 157-162 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hagiwara, K.: "Borna disease virus RNA in peripheral blood mononuclear cells obtained from healthy dairy cattle." Med. Microbiol. Immunol.185・3. 145-151 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hagiwara, K.: "High prevalence of Borna disease virus infection in healthy sheep in Japan." Ciln. Diagn. Lab. Immunol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Hagiwara, K.: "Demonstration of Borna disease virus (BDV) in specific regions of the brain from horses positive for serum antibodies to BDV but negative for BDV RNA in the blood and internal organs." Med. Microbiol. Immunol.(in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 中屋 隆明: "末梢血中のボルナ病ウイルスゲノムの検出-RT-PCR法による高感度RNAゲノム検出-" 蛋白質 核酸 酸素. 41・5. 194-198 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 生田 和良: "日本の動物および人におけるボルナ病ウイルス感染状況" 馬の科学. 33・3. 215-220 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 生田 和良: "慢性疲労症候群とウイルス感染" 医学のあゆみ. 177・13. 899-904 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 生田 和良: "ボルナ病ウイルスと精神疾患" 医学のあゆみ. 177・13. 905-909 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 生田 和良: "ボルナ病ウイルス" 感染症. 26・4. 21-24, 27-32 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 岩崎 和彦: "四国地方におけるボルナ病ウイルス(BDV)感染と精神分裂病との関連に関する疫学的調査(Part 1-臨床経過の検討)" 精神科治療学. 11・10. 1075-2078 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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