VIRUS-INDUCED AUTOIMMUNE MEDIATED ENCEPHALOMYELITIS

本研究是基于急性病毒感染的假设

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.