VIRUS-INDUCED AUTOIMMUNE MEDIATED ENCEPHALOMYELITIS

病毒引起的自身免疫介导的脑脊髓炎

基本信息

批准号：
3476784
负责人：
FOROOZAN MOKHTARIAN
金额：
$ 8.99万
依托单位：
MAIMONIDES MEDICAL CENTER (BROOKLYN)
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-12-01 至 1992-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3476784
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

项目摘要

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急性病毒的假设导致破坏和脱髓的感染中枢神经系统（CNS）可以触发自身免疫过程导致慢性脱髓鞘脑病，这样作为多发性硬化症（MS）。这项研究将调查免疫和臭名化反应的病理作用小鼠，Semliki森林病毒和信德氏病的急性病毒感染病毒诱导或增加了诱导的敏感性疾病过程类似于实验过敏性脑脊髓炎（eae）。 EAE，就临床和组织病理学而言特征是MS的最佳可用型号。具体该提案的目的是：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/或类型的正相关 EAE的炎症性浸润或病毒生长的程度易感和抗性菌株FO小鼠。 2）调查是否高于损害可以使小鼠灌注以免疫学对自己的髓磷脂的成分； 3）研究这些病毒感染是否可以增强和/或使动物诱发动物 EAE N EAE敏感和/或抗性小鼠；和4）确定大脑内SFV还是SV的持久性有助于随后的脱髓鞘的发病机理。短暂使用的方法包括（i）病毒的细胞和中枢神经系统切片的免疫组织化学染色 ABC技术感染动物的病理学决心。（ii）使用爆炸转化ELISA和蛋白质印迹以检测对纯化髓磷脂成分的反应（例如，MBP）; （iii）在易感性和抗性中诱导EAE 用抗原完全免疫的小鼠菌株 Freund的辅助和通过体外培养的转移淋巴细胞。（iv）原位杂交以检测病毒使用SV和 SFV。