2004 Fiscal Year Final Research Report Summary
Studies on the heterogeneity in the correlation between Borna disease virus location in the central nervous system(CNS) and induced CNS pathogenesis
Project/Area Number |
14370102
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Virology
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Research Institution | Osaka University |
Principal Investigator |
IKUTA Kazuyoshi Osaka University, Research Institute for Microbial Diseases Virology, Professor, 微生物病研究所, 教授 (60127181)
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Co-Investigator(Kenkyū-buntansha) |
TOMONAGA Keizo Osaka University, Research Institute for Microbial Diseases, Virology, Associate Professor, 微生物病研究所, 助教授 (10301920)
TSUJI Shotaro Osaka University, Research Institute for Microbial Diseases, Virology, Research Associate, 微生物病研究所, 助手 (30285192)
TANIYAMA Hiroyuki Rakuno Gakuen University, School of Veterinary Medicine, Veterinary Pathology, Professor, 獣医学部, 教授 (90133800)
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Project Period (FY) |
2002 – 2004
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Keywords | Borna disease virus / central nervous system / transgenic mouse / persistent infection / psychiatric disorder / stress / HMGB1 / phosphoprotein |
Research Abstract |
Borna disease virus(BDV) is a highly neurotropic, negative-, single-stranded RNA virus and is the etiological agent of Borna disease, encephalitis in horses and sheep. Infection with BDV in humans, especially in some of the patients with psychiatric disorders, was reported. In fact, BDV signals were identified in some of the autopsied brains from the BDV-seropositive patients. The objective in this study is to analyze the BDV virulence at in vivo and in vitro levels as well as molecular level in order to clarify the mechanism of BDV-induced pathogenesis at the central nervous system. Studies using neuronal cell cultures, revealed 1)the interaction between BDV p24 phosphoprotein (P) and multi-functional protein HMGB1 (also named amphoterin) ; 2)blocking of functions of HMGB1 by the interaction with P protein ; and 3)significant decrease of host anti-stress (such as heating) responses. In addition, we found that neurological symptoms were induced in the rats by stress (intraperitoneal injection with LPS) under the condition with persistent infection with BDV. Further, we prepared transgenic mice expressing BDVP protein under the GFAP promoter in the brain and found that the transgenic mice showed aggressive behavior and significant impairement of spatial reference memory, but no significant effect in the locomotor activity. These transgenic mice also showed the significant decreases in the levels of brain-derived neurotrophic factor(BDNF), synapse density, serotonin receptors (5-THR_<1A> and 5-THR_<1B>) in the brains. Thus, using several model systems, it was clarified that the CNS pathogenesis could appear by the persistent infection with BDV in the CNS.
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Research Products
(29 results)
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[Journal Article] Persistent Borna disease virus infection confers instability of HSP70 mRNA in glial cells during heat stress.2005
Author(s)
Yamashita, M., Kamitani, W., Yanai, H., Ohtaki, N., Watanabe, Y., Lee, B.J., Tsuji, S., Kobayashi, T., Ikuta, K., Tomonaga, K.
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Journal Title
J.Virol. 79-4
Pages: 2033-2041
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Arch.Virol. 148-8
Pages: 1557-1568
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Age- and host-dependent control of Borna disease virus spread in the developing brains of gerbils and rats.2003
Author(s)
Lee, B.-J., Watanabe, M., Yamashita, M., Kamitani, W., Kobayashi, T., Ikuta, K., Tomonaga, K.
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Journal Title
Microbes Infect. 5
Pages: 1195-1204
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Borna disease virus phosphoprotein represses p53-mediated transcriptional activity by interference with HMGB1.2003
Author(s)
Zhang, G., Kobayashi, T., Kamitani, W., Komoto, S., Yamashita, M., Baba, S., Yanai, H., Ikuta, K., Tomonaga, K.
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Journal Title
J.Virol. 77-22
Pages: 12243-12251
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Borna disease virus induces acute fatal neurological disorders in neonatal gerbils without virus- and immune-mediated cell destructions.2003
Author(s)
Watanabe, M., Lee, B.-J., Yamashita, M., Kamitani, W., Kobayashi, T., Tomonaga, K., Ikuta, K.
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Journal Title
Virology 310-2
Pages: 245-253
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Modulation of Borna disease virus phosphorotein Nuclear localixation by the viral protein X encoded in the overlapping open reading frame.2003
Author(s)
Kobayashi, T., Zhang, G., Lee, B.-J., Baba, S., Yamashita, M., Kamitani, W., Yanai, H., Tomonaga, K., Ikuta, K.
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Journal Title
J.Virol. 77
Pages: 8099-8107
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glial expression of Borna disease virus phosphoprotein induces behavioral and neurological abnormalities in transgenic mice.2003
Author(s)
Kamitani, W., Ono, E., Yoshino, S., Kobayashi, T., Taharaguchi, S., Lee, B-J., Yamashita, M., Kobayashi, T., Okamoto, M., Taniyama, H., Tomonaga, K., Ikuta, K.
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Journal Title
Proc.Natl.Acad.Sci.USA 100-15
Pages: 8969-8974
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nosological study of Borna disease virus infection in race horses.2002
Author(s)
Hagiwara, K., Okamoto, M., Kamitani, W., Takamura, S., Taniyama, H., Tsunoda, N., Tanaka, H., Iwai, H., Ikuta, K.
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Journal Title
Vet.Microbiol. 84-4
Pages: 367-374
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Varied persistent life cycles of Borna disease virus in a human oligodendroglioma cell line.2002
Author(s)
Ibrahim, M.S., Watanabe, M., Palacios, J.A., Kamitani, W., Komoto, S., Kobayashi, T., Tomonaga, K., Ikuta, K.
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Journal Title
J.Virol. 76-8
Pages: 3873-3880
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Borna disease in a heifer in Japan.2002
Author(s)
Okamoto, M., Furuoka, H., Hagiwara, K., Kamitani, W., Kirisawa, R., Ikuta, K., Taniyama, H.
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Journal Title
Vet.Rec. 150-1
Pages: 16-18
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Borna disease in a dog in Japan.2002
Author(s)
Okamoto, M., Kagawa, Y., Hagiwara, K., Kirisawa, R., Kamitani, W., Ikuta, K., Taniyama, H.
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Journal Title
J.Comp.Pathol. 126-4
Pages: 312-317
Description
「研究成果報告書概要(欧文)」より
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