ROLE OF MICROGLIA IN THEILER'S VIRUS INFECTION

小胶质细胞是驻留在中枢神经系统(CNS)的巨噬细胞。当中枢神经系统受到损伤或感染时，它们就会被激活。泰勒氏小鼠脑脊髓炎病毒(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确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，本研究建议确定小胶质细胞在脱髓鞘疾病的发生和延续中的作用。首先，将研究小胶质细胞，以确定它们在导致中枢神经系统脱髓鞘疾病的病毒持久性中的作用。其次，将检测小胶质细胞在病毒感染过程中作为抗原提呈细胞的作用，以确定小胶质细胞是否呈现病毒表位。最初的免疫反应导致组织损伤和针对髓鞘蛋白的自身免疫反应的启动。下一步，将研究小胶质细胞呈递髓鞘表位的能力，以了解它们在加剧脱髓鞘过程中的作用。因此，本研究将确定小胶质细胞作为驻留在中枢神经系统的巨噬细胞在TMEV诱导的自身免疫性脱髓鞘疾病中可能扮演的各种角色。

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.