Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-3-23
pubmed:abstractText
E2 is an important determinant of Sindbis virus neurovirulence. Increased heparan sulfate (HS) binding is associated with rapid clearance of viremia and usually with decreased virulence. However, substitution of histidine for arginine at E2-157 (R157H) or glutamate for lysine at E2-159 (K159E) produces viruses with decreases in heparin-Sepharose binding and increases in viremia but different levels of binding to HS-expressing cells and virulence phenotypes in newborn CD-1 mice (Byrnes, A.P., Griffin, D.E., 2000. Large-plaque mutants of Sindbis virus show reduced binding to heparan sulfate, heightened viremia and slower clearance from the circulation. J. Virol. 74, 644-651). To identify mechanisms of virulence, R157H and K159E were studied in newborn CD-1 and BALB/c mice. Subcutaneous inoculation of R157H caused 100% and K159E 60% mortality in 2-day-old CD-1 mice. R157H caused 25% and K159E no mortality in 2-day-old BALB/c mice. R157H and K159E replicated similarly at the site of inoculation with the same level of viremia, but clearance was slower in CD-1 than BALB/c mice. R157H replicated better than K159E in the central nervous system (CNS) after subcutaneous and intracerebral inoculation and in undifferentiated neurons. These studies show a genetic restriction of replication in newborn BALB/c mice, and that amino acid substitutions affecting binding to proteoglycans may differ in importance for CNS infection and viremia.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0042-6822
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
347
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
183-90
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Heparin-binding and patterns of virulence for two recombinant strains of Sindbis virus.
pubmed:affiliation
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St., Rm. E5132, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural