VIRUS-INDUCED AUTOIMMUNE MEDIATED ENCEPHALOMYELITIS

病毒引起的自身免疫介导的脑脊髓炎

• 批准号: 3476782
• 负责人: FOROOZAN MOKHTARIAN
• 金额: $ 8.16万
• 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/3476782
• 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.

这项拟议的研究基于以下假设：急性病毒 导致髓鞘破坏和脱髓鞘的感染 中枢神经系统（CNS）可以触发自身免疫过程 这会导致慢性脱髓鞘性脑炎疾病，例如 如多发性硬化症（MS）。 本研究将调查 免疫和炎症反应对两种疾病的病理作用 小鼠急性病毒感染，塞姆利基森林病毒和辛德比斯病毒 病毒诱导或增加对诱导的易感性 疾病过程与实验性过敏性脑脊髓炎相似 （EAE）。 EAE，在临床和组织病理学方面 特点，是 MS 的最佳可用模型。 具体的 该提案的目的是： 1) 调查是否发生 病毒感染动物的急性麻痹和脱髓鞘是 与严重程度和/或类型呈正相关 EAE 中炎症浸润或病毒生长程度 小鼠的敏感品系和耐药品系。 2) 调查是否 上述损伤可以促使小鼠做出免疫反应 其自身髓磷脂的成分； 3）研究这些病毒感染是否 可以增强和/或使动物易于诱导 EAE 分别指 EAE 易感和/或耐药小鼠；和 4) 确定 SFV 或 SV 是否在大脑中持续存在 有助于随后脱髓鞘的发病机制。 简要采用的方法包括 (i) 病毒细胞和中枢神经系统切片的免疫组织化学染色 采用ABC技术对感染动物进行病理学检查 决心。 (ii) 使用母细胞转化 ELISA 和 蛋白质印迹检测对纯化髓磷脂成分的反应 （例如，MBP）； (iii) 在易感者和耐药者中诱导EAE 用抗原完全免疫的小鼠品系 弗氏佐剂并通过体外培养转移 淋巴细胞。 (iv) 用于检测病毒的原位杂交 使用 SV 和 cDNA 探针检测受感染 CNS 组织中的 RNA SFV。