Downregulation of an astrocyte-derived inflammatory protein, S100B, reduces vascular inflammatory responses in brains persistently infected with Borna disease virus
Downregulation of an astrocyte-derived inflammatory protein, S100B, reduces vascular inflammatory responses in brains persistently infected with Borna disease virus
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DOI：
10.1128/jvi.02137-06
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Tomonaga, Keizo
中科院分区：
文献类型：
--
作者：
Ohtaki, Naohiro;Kamitani, Wataru;Tomonaga, Keizo
博尔纳病病毒(BDV)是一种嗜神经性病毒，在许多脊椎动物的中枢神经系统(CNS)中引起持续感染。尽管在实验感染BDV的大鼠脑中观察到了严重的反应性胶质细胞增生，但对导致病毒在中枢神经系统持续存在和免疫调节的胶质反应知之甚少。在这方面，我们检测了持续感染BDV的Lewis大鼠大脑中星形细胞衍生因子S100B的表达。S100B是一种主要由星形胶质细胞产生的钙结合蛋白。该蛋白的一个突出作用似乎是通过与晚期糖基化终产物受体(RAGE)的相互作用来促进血管炎症反应。在这里，我们发现，在BDV感染的大脑中，S100B的表达显著减少，尽管严重的星形细胞增多，胶质纤维酸性蛋白免疫反应性增加。有趣的是，在持续感染的大脑中，即使在包括内毒素在内的几种炎症刺激下也没有观察到S100B或RAGE的表达上调。此外，在用髓鞘碱性蛋白免疫诱导实验性自身免疫性脑脊髓炎的持续感染的脑中，血管细胞黏附分子1(VCAM1)的表达以及脑源性T细胞的渗透显著减少。此外，我们还证明，S100B在脑内的持续激活可能是新生感染大鼠脑血管免疫反应进展所必需的。我们的结果提示，BDV感染可能通过下调S100B的表达而损害星形胶质细胞的功能，导致持续感染。
Borna disease virus (BDV) is a neurotropic virus that causes a persistent infection in the central nervous system (CNS) of many vertebrate species. Although a severe reactive gliosis is observed in experimentally BDV-infected rat brains, little is known about the glial reactions contributing to the viral persistence and immune modulation in the CNS. In this regard, we examined the expression of an astrocyte-derived factor, S100B, in the brains of Lewis rats persistently infected with BDV. S100B is a Ca2+ -binding protein produced mainly by astrocytes. A prominent role of this protein appears to be the promotion of vascular inflammatory responses through interaction with the receptor for advanced glycation end products (RAGE). Here we show that the expression of S100B is significantly reduced in BDV-infected brains despite severe astrocytosis with increased glial fibrillary acidic protein immumoreactivity. Interestingly, no upregulation of the expression of S100B, or RAGE, was observed in the persistently infected brains even when incited with several inflammatory stimuli, including lipopolysaccharide. In addition, expression of the vascular cell adhesion molecule 1 (VCAM1), 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 myelinbasic protein. Furthermore, we demonstrated that the continuous activation of S100B 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.