Linked Life Data

7693969

Source:http://linkedlifedata.com/resource/pubmed/id/7693969

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1993-12-21
pubmed:abstractText
This study documents that the immunosuppressive lymphocytic choriomeningitis virus (LCMV) variant, clone 13, shows a specific predilection for enhanced infection of macrophages both in vitro and in vivo and that single amino acid changes in the viral polymerase and glycoprotein are responsible for macrophage tropism. The growth difference seen between variant clone 13 and the parental Armstrong strain was specific for macrophages, since both clone 13 and Armstrong grew equally well in fibroblasts and neither isolate infected lymphocytes efficiently. Complete sequencing of the clone 13 genome, along with genetic analysis, showed that a single amino acid change in the polymerase (K-->Q at position 1079) was the major determinant of virus yield in macrophages. This was proven unequivocally by comparing the sequences of parental and reassortant viruses, which were identical at all loci except for the single mutation in the polymerase gene. This finding was further strengthened by showing that reversion at this site back to lysine (Q-->K) resulted in loss of macrophage tropism. In addition, an independently derived macrophage-tropic variant of LCMV, clone 28b, had a K-->N mutation at the same position. Thus, these results show that substitution of the positively charged amino acid K with a neutral amino acid (either Q or N) at residue 1079 of the polymerase resulted in enhanced viral replication in macrophages. In addition to the polymerase change, a mutation in the glycoprotein was also associated with macrophage tropism. This single amino acid change in the glycoprotein (F-->L at position 260) did not affect virus yield per macrophage but was critical in determining the number of macrophages infected. Our previous studies have shown that the same two mutations in the polymerase and glycoprotein are essential for establishing a chronic infection in adult mice. Since the same mutations confer macrophage tropism and ability to persist in vivo, these studies provide compelling evidence that infection of macrophages is a critical determinant of viral persistence and immune suppression.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-110886, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-1394431, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-13955006, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-1626415, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-1727490, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-1905339, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-1976825, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2072451, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2172833, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2185332, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2212940, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2422213, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2440339, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2510401, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2705303, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-2898508, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3014648, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3019106, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3259346, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3261347, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3367096, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3392416, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3500329, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3682061, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-3824905, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-6170937, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-6332167, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-6355856, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-7308288, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-8393233, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-8419647, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-8469287, http://linkedlifedata.com/resource/pubmed/commentcorrection/7693969-8515132
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-538X
pubmed:author
pubmed:issnType
Print
pubmed:volume
67
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7340-9
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus.
pubmed:affiliation
Department of Microbiology and Immunology, University of California, Los Angeles School of Medicine 90024-1747.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't