The role of interferons in the neuropathogenesis of Theiler's virus /
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination (TVID) has many features in common with multiple sclerosis (MS), and therefore offers an excellent model system in which pathogenesis of and therapeutic strategies for MS can be studied. TMEV is classified into the virulent s...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1999.
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| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=731685941&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Theiler's murine encephalomyelitis virus (TMEV)-induced demyelination (TVID) has many features in common with multiple sclerosis (MS), and therefore offers an excellent model system in which pathogenesis of and therapeutic strategies for MS can be studied. TMEV is classified into the virulent strains (GDVII and FA) which cause fatal encephalitis in all strains of mice and the non-virulent strains (BeAn and DA) which cause persistent infection of the CNS and subsequent demyelination in certain susceptible strains of mice. Both the mechanisms of disease susceptibility and viral persistence remain unresolved questions within the TVID model. Breakdown of the blood-brain barrier (BBB) occurs prior to MS relapses and is a possible route of viral infection of the CNS. Therefore, events that occur at the BBB are crucial in understanding the pathogenesis of demyelination. The hypothesis to be tested in the present study is that differential IFN responses within the BBB account, in part, for the disease phenotype of TVD. TMEV infection of cerebrovascular endothelial (CVE) cells (that form the BBB) derived from TVID-susceptible SJL/W mice induced the expression of MHC class I antigen via the production of IFN-α/β. In contrast, TMEV infection of CVE derived from TVID-resistant BALB/c mice resulted in the production of biologically active IFN-α/β, but no surface MHC class I expression was detectable. Examination of the molecular components of MHC class 1 revealed that BALB/c CVE may not be responding to IFN-α/β at some stage between MHC class I heavy chain transcription and translation. IFN-α/β has been shown to be beneficial in the treatment of MS. Therefore, this study also investigated the possible role of IFN-[], a novel type I interferon, as a therapeutic agent in the context of the TVID model. It was demonstrate that IFN-[] was able to down-regulate IFN-γ-induced MHC class II expression on CVE and hence could be of therapeutic value in down-regulating inflammation in the CNS. Furthermore, the virulent GDVII strain of TMEV was found to be more sensitive to IFN-α/β than the non-virulent strains, suggesting that insensitivity to IFN-α/β may be a mechanism of viral persistence used by the To strains of TMEV. |
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| Item Description: | Vita. "Major Subject: Veterinary Anatomy". |
| Physical Description: | xiv, 184 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 156-183). |