| Project/Area Number |
15390148
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Osaka University |
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Principal Investigator |
TOMONAGA Keizo Osaka University, Research Institute for Microbial Diseases, Associate Professor, 微生物病研究所, 助教授 (10301920)
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| Co-Investigator(Kenkyū-buntansha) |
IKUTA Kazuyoshi Osaka University, Research Institute for Microbial Diseases, Professor, 微生物病研究所, 教授 (60127181)
ONO Etsuro Tottori University, The Avian Zoonosis Research Centre, Professor, 鳥由来人獣共通感染症疫学研究センター, 教授 (00160903)
辻 祥太郎 大阪大学, 微生物病研究所, 助手 (30285192)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥15,200,000 (Direct Cost: ¥15,200,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Borna disease virus / Central nervous system / Persistent Infection / RAGE / Viral neuropathogenesis / CNS immunity / 感染病態 |
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| Research Abstract |
Borna disease virus (BDV) belongs to the Bornaviridae family, within the nonsegmented negative-strand RNA virus, Mononegavirales, which is characterized by highly neurotropic, noncytopathic replication, and persistent infection. Although previous studies using rodent models indicated that modulation of the immune response, such as BDV-specific Thl tolerance, could contribute to the induction of persistence in the brain, the mechanisms by which CNS viruses efficiently control immune response have not been yet fully elucidated. In this study, to understand the strategy that neurotropic virus evades host response, we investigated the role of the receptor for advanced lycation end products (RAGE), which is involved in the immune system's response pathways, in BDV-infected brains. Newborn or 4-weeks old Lewis rats were intracranially inoculated with BDV. To examine the role of RAGE in CNS virus infection, expression level of RAGE and its ligands was traced with the viral propagation. We found that RAGE expression gradually decreased in BDV-infected brain in correlation with viral propagation despite the upregulation of potent RAGE ligands, such as HMGB1 and S100B. Interestingly, BDV persistent brains displayed no reactivation of the RAGE expression and reduced reaction to the induction of inflammatory response even by the injection of several antigens. In experimental autoimmune encephalomyelitis, persistently infected rats induced only mild inflammation in the cerebellum. We demonstrated the downregulation of RAGE expression in the brain persistently infected with BDV. Resent reports have revealed that RAGE is involved in the host immune reaction and its expression might be required for the perpetuation of the innate immune response. Our observations suggested that BDV infection could escape form the inflammatory response by the regulation of RAGE expression in the brain, leading to the development of persistent infection.
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