VIRUS-INDUCED AUTOIMMUNE MEDIATED ENCEPHALOMYELITIS

这项拟议的研究是基于以下假设：急性病毒 感染导致髓鞘的破坏和脱髓鞘 中枢神经系统(CNS)可触发自身免疫过程 这会导致慢性脱髓鞘脑炎疾病，如 多发性硬化症(MS)。这项研究将调查 免疫和炎症反应在两种疾病中的病理作用 小鼠、森姆利基森林病毒和辛德比斯的急性病毒感染 病毒诱导或增加对诱导的易感性 类似于实验性变态反应性脑脊髓炎的疾病过程 (EAE)。临床和组织病理学方面的EAE 特点，是目前可供选择的最适合女士的模式 这项建议的目的是：1)调查是否发生了 病毒感染动物的急性瘫痪和脱髓鞘 与严重程度和/或类型呈正相关 EAE中的炎性浸润或病毒生长的程度 对小鼠敏感和耐药的菌株。2)调查是否 上述损伤可以使小鼠对 自身髓鞘的成分；3)研究这些病毒感染 可以增强和/或使动物易于诱发 EAE易感和/或耐药小鼠；以及4) 以确定SFV或SV在脑内的持久性 有助于随后脱髓鞘的发病机制。 拟采用的方法简要包括(I) 病毒细胞和中枢神经系统切片的免疫组织化学染色 应用ABC技术对感染动物进行病理检查 决心。(Ii)使用BLAST转化酶联免疫吸附试验和 免疫印迹法检测对纯化髓鞘成分的反应 (3)诱导易感和抗病EAE 用完全抗原免疫的小鼠品系 弗氏佐剂和转移法体外培养 淋巴细胞。(Iv)检测病毒的原位杂交 用SV和Sv基因探针检测感染中枢神经系统组织中的RNA SFV。

This proposed study is based on the hypothesis that acute viral infections which result in the destruction and demyelinaton of the central nervous system (CNS) can trigger an autoimmune process which leads to a chronic demyelinating encephalitic disease, such as multiple sclerosis (MS). This study will investigate the pathologic role of immune and infammatory responses to two acute viral infections of mice, Semliki Forest Virus and Sindbis Virus to induce, or increase, susceptibility to the induction of a disease process similar to experimental allergic encephalomyelitis (EAE). EAE, in terms of clinical and histopathological characteristics, is the best available model for MS. The specific aims of this proposal are: 1) To investigate if the occurrence of acute paralysis and demyelination in virus infected animals is positively correleated with the severity and/or type of inflammatory infiltrates or the extent of viral growth in EAE susceptible and resistant strains fo mice. 2) To investigate if the above damage can prime the mice to respond immunologically to components of its own myelin; 3) To study if these viral infections can potentiate and/or predispose the animals to the induction of EAE n EAE-susceptible and/or resistant mice respectively; and 4) To determine whether persistence of SFV or SV within the brain contributes to the pathogenesis of subsequent demyelination. The methods to be employed briefly include (i) immunohistochemical staining of cells and CNS sections of virus- infected animals by ABC technique for pathological determination. (ii) Use of blast transformation ELISA and western blot to detect responses to purified myelin components (e.g., MBP); (iii) Induction of EAE in susceptible and resistant strains of mice by immunization with antigen in complete Freund's adjuvent and by transfer of in vitro cultured lymphocytes. (iv) In situ hybridization for the detection of viral RNA in the infected CNS tissue using cDNA probes of SV and SFV.