THEILERS VIRUS CODING REGIONS IMPORTANT IN DEMYELINATION

本研究项目的长期目标是确定 泰勒氏鼠脑脊髓炎病毒（TMEV）的蛋白编码区 在产生T细胞介导的免疫应答中重要的基因组 负责抵抗病毒感染和/或发展 脱髓鞘疾病我们会让老鼠对某些 的TMEV编码区，然后用活病毒感染。我们的第一 目的是描述三种临床和病理变化 表达TMEV连续区域的转基因小鼠品系 包括整个病毒基因组。转基因小鼠将被 用脱髓鞘滴度的TMEV攻击并检查。第二 目的是用牛痘病毒感染成年小鼠， 病毒重组体表达区域和整个TMEV基因组， 然后感染TMEV。我们希望一些TMEV 表达TMEV部分的抗性单倍型转基因小鼠 负责保护性免疫反应将脱髓鞘，而 表达TMEV部分的易感单倍型转基因小鼠 负责破坏性免疫反应不会脱髓鞘。在 相反，用牛痘病毒重组体免疫的抗性株 表达TMEV负责破坏性反应的部分可能成为 对活病毒易感，自发脱髓鞘或继发脱髓鞘 感染这些研究与MS有很大的相关性，MS是一种 自身抗原特异性T细胞被怀疑参与慢性 髓鞘损伤

The long term objective of this research project is to determine the protein coding regions of Theiler's murine encephalomyelitis virus (TMEV) genome important in generating the T cell-mediated immune response responsible for resistance to virus infection and/or development of demyelinating disease. We will tolerize and immunize mice against parts of TMEV coding regions followed by infection with live virus. Our first aim is to characterize the clinical and pathological changes of three lines of transgenic mice expressing contiguous regions of TMEV encompassing the entire viral genome. The transgenic mice will then be challenged with a demyelinating titer of TMEV and examined. The second aim is to immunize adult mice against TMEV by infecting with vaccinia virus recombinants expressing regions and the entire TMEV genome, followed by infection with TMEV. We expect that some of the TMEV transgenic mice of resistant haplotypes expressing the parts of TMEV responsible for protective immune response will demyelinate, whereas transgenic mice of susceptible haplotypes expressing parts of TMEV responsible for destructive immune response will not demyelinate. In contrast, resistant strains immunized with vaccinia virus recombinant expressing parts of TMEV responsible for destructive response may become susceptible, demyelinating spontaneously or subsequent to live virus infection. These studies have great relevance to MS, a disease in which autoantigen-specific T cells are suspected to be involved in chronic myelin damage.