VIRUS-INDUCED AUTOIMMUNE MEDIATED ENCEPHALOMYELITIS

病毒引起的自身免疫介导的脑脊髓炎

• 批准号: 3476783
• 负责人: FOROOZAN MOKHTARIAN
• 金额: $ 8.35万
• 依托单位: MAIMONIDES MEDICAL CENTER (BROOKLYN)
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-12-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3476783
• 关键词: Semliki Forest virus; autoimmune disorder; disease /disorder model; experimental allergic encephalomyelitis; immunochemistry; in situ hybridization; laboratory mouse; multiple sclerosis; myelinopathy; nucleic acid hybridization; nucleic acid probes; simian virus 40; tissue /cell culture; virus cytopathogenic effect; virus infection mechanism; virus replication

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.

这项拟议的研究是基于这样一种假设，即急性病毒性 感染，导致破坏和脱髓鞘的 中枢神经系统（CNS）可引发自身免疫过程 导致慢性脱髓鞘性脑炎， 多发性硬化症（MS） 本研究将探讨 免疫和炎症反应的病理作用 小鼠急性病毒感染、塞姆利基森林病毒和辛德毕斯病毒 病毒诱导，或增加，易感性的诱导， 类似实验性变态反应性脑脊髓炎的病程 （EAE）。 EAE，临床和组织病理学方面 特性，是MS的最佳可用模型。 这项建议的目的是：1）调查是否发生 病毒感染动物的急性麻痹和脱髓鞘， 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程度 敏感品系和抗性品系。 2)去调查 上述损伤可以激发小鼠对 3）研究这些病毒感染是否会影响其自身的髓鞘成分 可以增强和/或使动物容易诱发 EAE分别为EAE敏感和/或抗性小鼠;和4） 为了确定脑内SFV或SV的持续存在是否 有助于随后的脱髓鞘的发病机制。 所采用的方法简要包括（一） 病毒的细胞和CNS切片的免疫组织化学染色- 用ABC技术对感染动物进行病理学检查 保持战略定力 (ii)使用胚细胞转化ELISA和 蛋白质印迹法检测对纯化髓磷脂组分的反应 (e.g.,（iii）在易感和抗性小鼠中诱导EAE 用抗原免疫小鼠， 弗氏佐剂和通过转移体外培养 淋巴细胞 (iv)原位杂交检测病毒 使用SV和SV的cDNA探针检测感染CNS组织中的RNA， SFV