Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-1-21
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-24
pubmed:dateRevised
2007-11-14
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
pubmed:year
1999
pubmed:articleTitle
A Theiler's virus alternatively initiated protein inhibits the generation of H-2K-restricted virus-specific cytotoxicity.
pubmed:affiliation
Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't