ROLE OF MICROGLIA IN THEILER'S VIRUS INFECTION

小胶质细胞是中枢神经系统（CNS）中的常驻巨噬细胞。它们在CNS损伤或感染时被激活。Theiler鼠脑脊髓炎病毒（TMEV）感染导致SJL小鼠中枢神经系统发生自身免疫性脱髓鞘疾病。TMEV诱导的脱髓鞘疾病已被鉴定为人类多发性硬化症的模型。这两种疾病有几个相似之处。先前的研究表明，小胶质细胞存在于这两种脱髓鞘疾病的早期病变中。本研究旨在确定小胶质细胞在脱髓鞘疾病的起始和持续中的作用。首先，将研究小胶质细胞以确定它们在导致CNS脱髓鞘疾病的病毒持续存在中的作用。其次，将检查小胶质细胞在病毒感染期间作为抗原呈递细胞的作用以确定小胶质细胞是否呈递病毒表位。最初的免疫应答导致组织损伤和针对髓鞘蛋白的自身免疫应答的启动。接下来，将研究小胶质细胞呈递髓鞘表位的能力，以确定其在脱髓鞘加重中的作用。因此，本研究将确定作为CNS中的驻留巨噬细胞的小胶质细胞在TMEV诱导的自身免疫性脱髓鞘疾病中可能发挥的各种作用。

Microglia are resident macrophages in the central nervous system (CNS). They become activated upon injury or infection in the CNS. Theiler's murine encephalomyelitis virus (TMEV) infection causes development of an autoimmune demyelinating disease in the CNS of SJL mice. TMEV induced demyelinating disease has been identified as a model for multiple sclerosis in humans. The two diseases share several similarities. Previous studies have shown that microglia are present in the early lesions of both of these demyelinating diseases This study proposes to determine the role of microglia in the initiation and continuation of the demyelinating disease. First, microglia will be studied to determine their role in viral persistence which leads to the demyelinating disease in the CNS. Second, the role of microglia as antigen presenting cells during the viral infection will be examined to determine whether microglia present viral epitopes. The initial immune response leads to tissue damage and the initiation of the autoimmune response against myelin proteins. Next, the ability of microglia to present myelin epitopes will be studied for their role in the exacerbation of the demyelination. Thus, this study will determine the various roles microglia as resident macrophages in the CNS may play in TMEV induced autoimmune demyelinating disease.