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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-10-2
pubmed:abstractText
The mouse hepatitis virus (MHV) spike glycoprotein is a major determinant of neurovirulence. We investigated how alterations in spike affect neurovirulence using two isogenic recombinant viruses differing exclusively in spike. S(4)R, containing the MHV-4 spike gene, is dramatically more neurovirulent than S(A59)R, containing the MHV-A59 spike gene (J. J. Phillips, M. M. Chua, E. Lavi, and S. R. Weiss, 1999, J. Virol. 73, 7752-7760). We examined the contribution of differences in cellular tropism, viral spread, and the immune response to infection to the differential neurovirulence of S(4)R and S(A59)R. MHV-4 spike-mediated neurovirulence was associated with extensive viral spread in the brain in both neurons and astrocytes. Infection of primary hippocampal neuron cultures demonstrated that S(4)R spread more rapidly than S(A59)R and suggested that spread may occur between cells in close physical contact. In addition, S(4)R infection induced a massive influx of lymphocytes into the brain, a higher percentage of CD8(+) T cells, and a higher frequency of MHV-specific CD8(+) T cells relative S(A59)R infection. Despite this robust and viral-specific immune response to S(4)R infection, infection of RAG1-/- mice suggested that immune-mediated pathology also contributes to the high neurovirulence of S(4)R.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
301
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
109-20
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Murine coronavirus spike glycoprotein mediates degree of viral spread, inflammation, and virus-induced immunopathology in the central nervous system.
pubmed:affiliation
Department of Microbiology, University of pennsylvania School of Medicine, Philadelphia 19104-6076, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.