Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2008-11-12
pubmed:abstractText
The inherent sequence diversity of the hepatitis C virus (HCV) represents a major hurdle for the adaptive immune system to control viral replication. Mutational escape within targeted CD8 epitopes during acute HCV infection has been well documented and is one possible mechanism for T-cell failure. HLA-B*08 was recently identified as one HLA class I allele associated with spontaneous clearance of HCV replication. Selection of escape mutations in the immunodominant HLA-B*08-restricted epitope HSKKKCDEL(1395-1403) was observed during acute infection. However, little is known about the impact of escape mutations in this epitope on viral replication capacity. Their previously reported reversion back toward the consensus residue in patients who do not possess the B*08 allele suggests that the consensus sequence in this epitope is advantageous for viral replication in the absence of immune pressure. The aim of this study was to determine the impact of mutational escape from this immunodominant epitope on viral replication. We analyzed it with a patient cohort with chronic HCV genotype 1b infection and in a single-source outbreak (genotype 1b). Sequence changes in this highly conserved region are rare and selected almost exclusively in the presence of the HLA-B*08 allele. When tested in the subgenomic replicon (Con1), the observed mutations reduce viral replication compared with the prototype sequence. The results provide direct evidence that escape mutations in this epitope are associated with fitness costs and that the antiviral effect of HLA-B*08-restricted T cells is sufficiently strong to force the virus to adopt a relatively unfavorable sequence.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-10869294, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-11129633, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-11754811, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-12584326, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-15239092, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-15479787, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-15611288, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-15939788, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-15939790, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-15939791, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-15962289, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-16105887, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-16188997, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-16309340, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-16537629, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-16814596, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-16997629, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17071929, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17258731, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17263143, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17484874, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17559151, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17728232, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17804494, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-17935228, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-18025038, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-18086851, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-7679646, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-9018241, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-9187654, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-9493270, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-9560386, http://linkedlifedata.com/resource/pubmed/commentcorrection/18815309-9756471
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1098-5514
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11803-12
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Escape from HLA-B*08-restricted CD8 T cells by hepatitis C virus is associated with fitness costs.
pubmed:affiliation
University of Essen, Department of Virology, Virchowstrasse 179, 45147 Essen, Germany.
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