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Overcome of virus-induced neurological disorders : a novel strategy based on the functions of a pattern recognition receptor, RAGE

克服病毒引起的神经系统疾病：基于模式识别受体 RAGE 功能的新策略

基本信息

批准号：
18390139
负责人：
TOMONAGA Keizo
金额：
$ 9.74万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

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 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. Furthermore, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this study, we investigated the role of a pattern recognition receptor, RAGE (receptor for advanced glycation end products), which is involved in the immune system's response pathways, as well as an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. A prominent role of S100B appears to be the promotion of vascular inflammatory resp … More onses through interaction with the RAGE. We demonstrated that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immunoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even on incitation with several inflammatory stimuli, including lipopolysaccharide. In addition, the expression of the vascular cell adhesion molecule, VCAM-1, as well as the infiltration of encephalitogenic T-cells, was significantly reduced in persistently infected brains in which an experimental autoimmune encephalomyelitis was induced by immunization with myelin-basic protein. Furthermore, we demonstrated that the continuous activation of S1008 in the brain may be necessary for the progression of vascular immune responses in neonatally infected rat brains. Our results suggested that BDV infection may impair astrocyte functions via a downregulation of S100B expression, leading to the maintenance of a persistent infection. Less

博尔纳病病毒（Borna disease virus，BDV）属于博尔纳病毒科（Bornaviridae），属于单负链RNA病毒目（Mononegavirales），其特征在于高度嗜神经性、非细胞病变性复制和持续感染。尽管先前使用啮齿动物模型的研究表明，免疫应答的调节可能有助于诱导脑中的持久性，但CNS病毒有效控制免疫应答的机制尚未完全阐明。此外，很少有人知道神经胶质反应有助于病毒的持久性和免疫调节中枢神经系统。在这项研究中，我们研究了模式识别受体的作用，β-淀粉样蛋白（晚期糖基化终产物受体），这是参与免疫系统的反应途径，以及星形胶质细胞衍生因子，S100 B，在刘易斯大鼠持续感染BDV的大脑。S100 B的一个突出作用似乎是促进血管炎症反应。 ...更多信息通过与客户的互动。我们证明，S100 B的表达显着减少，尽管严重的星形胶质细胞增多，神经胶质细胞酸性蛋白的免疫反应性在BDV感染的大脑。有趣的是，在持续感染的大脑中没有观察到S100 B或S100 B的表达上调，即使在用几种炎症刺激物（包括脂多糖）刺激时也是如此。此外，表达的血管细胞粘附分子，VCAM-1，以及脑致炎性T细胞的浸润，显着减少在持续感染的大脑中，实验性自身免疫性脑脊髓炎诱导免疫与髓鞘碱性蛋白。此外，我们证明了S1008在脑中的持续激活可能是必要的血管免疫反应的进展，在脑内感染的大鼠大脑。我们的研究结果表明，BDV感染可能会损害星形胶质细胞功能，通过下调S100 B的表达，导致持续感染的维持。少