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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1999-1-21
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pubmed:abstractText |
In susceptible mouse strains, the wild-type Daniel's (wt-DA) strain of Theiler's murine encephalomyelitis virus induces a persistent central nervous system (CNS) infection with chronic demyelination. The virus is cleared from resistant mice with no resulting demyelination. We characterized the role of the DA L* protein in late demyelination and persistent infection. The DA genome has two alternative reading frames, encoding the virus polyprotein and L*, respectively. The mutant virus DAL*-1 fails to synthesize L* and does not persist in the CNS of wt-DA-susceptible SJL/J or B10.S mice. Since class I-restricted cytotoxicity has been shown to determine resistance to virus persistence and demyelination in this model, virus-specific cytotoxicity in the CNS of DA-resistant (B6 or B10) and -susceptible (SJL/J and B10.S) mice during the acute stage of DA and DAL*-1 infection was characterized. Following intracerebral inoculation with DAL*-1, virus-specific Db- and Kb-restricted CTLs were demonstrated in the CNS of resistant B10 mice, whereas only Db-restricted CTL were found in wt-DA-inoculated mice. CTLs specific to wt-DA or DAL*-1 recognized class I-presented peptides from either of the viruses. Of particular interest, Ks-restricted virus-specific cytotoxicity-restricted CTLs were identified in the CNS of susceptible SJL/J (H-2s) and B10.S (H-2s) mice inoculated with DAL*-1. In contrast, no virus-specific CTLs were identified in the CNS of SJL/J and B10.S mice inoculated with wt-DA. We propose that L* inhibits the generation of H-2K-restricted virus-specific cytotoxicity in the CNS, permitting a persistent infection in susceptible strains, with subsequent inflammatory demyelination in the CNS similar to that in human multiple sclerosis.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/H-2K(K) antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class II,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Leucine,
http://linkedlifedata.com/resource/pubmed/chemical/Viral Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/histocompatibility antigen H-2D(b)
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
162
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17-24
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9886365-Alternative Splicing,
pubmed-meshheading:9886365-Animals,
pubmed-meshheading:9886365-Antibodies, Viral,
pubmed-meshheading:9886365-Brain Diseases,
pubmed-meshheading:9886365-Cytotoxicity, Immunologic,
pubmed-meshheading:9886365-Demyelinating Diseases,
pubmed-meshheading:9886365-H-2 Antigens,
pubmed-meshheading:9886365-Histocompatibility Antigens Class II,
pubmed-meshheading:9886365-Immunosuppressive Agents,
pubmed-meshheading:9886365-Leucine,
pubmed-meshheading:9886365-Lymphocyte Activation,
pubmed-meshheading:9886365-Mice,
pubmed-meshheading:9886365-Mice, Inbred C57BL,
pubmed-meshheading:9886365-Mice, Inbred Strains,
pubmed-meshheading:9886365-Mice, Knockout,
pubmed-meshheading:9886365-Spinal Diseases,
pubmed-meshheading:9886365-Spleen,
pubmed-meshheading:9886365-Theilovirus,
pubmed-meshheading:9886365-Viral Proteins
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pubmed:year |
1999
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pubmed:articleTitle |
A Theiler's virus alternatively initiated protein inhibits the generation of H-2K-restricted virus-specific cytotoxicity.
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pubmed:affiliation |
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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