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dc.contributor.author Fischer, W
dc.contributor.author Ganusov, VV
dc.contributor.author Giorgi, EE
dc.contributor.author Hraber, PT
dc.contributor.author Keele, BF
dc.contributor.author Leitner, T
dc.contributor.author Han, CS
dc.contributor.author Gleasner, CD
dc.contributor.author Green, L
dc.contributor.author Lo, CC
dc.contributor.author Nag, A
dc.contributor.author Wallstrom, TC
dc.contributor.author Wang, S
dc.contributor.author McMichael, AJ
dc.contributor.author Haynes, BF
dc.contributor.author Hahn, BH
dc.contributor.author Perelson, AS
dc.contributor.author Borrow, P
dc.contributor.author Shaw, GM
dc.contributor.author Bhattacharya, T
dc.contributor.author Korber, BT
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:32:13Z
dc.date.issued 2010-08-20
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20808830
dc.identifier.citation PLoS One, 2010, 5 (8), pp. e12303 - ?
dc.identifier.uri http://hdl.handle.net/10161/4566
dc.description.abstract We used ultra-deep sequencing to obtain tens of thousands of HIV-1 sequences from regions targeted by CD8+ T lymphocytes from longitudinal samples from three acutely infected subjects, and modeled viral evolution during the critical first weeks of infection. Previous studies suggested that a single virus established productive infection, but these conclusions were tempered because of limited sampling; now, we have greatly increased our confidence in this observation through modeling the observed earliest sample diversity based on vastly more extensive sampling. Conventional sequencing of HIV-1 from acute/early infection has shown different patterns of escape at different epitopes; we investigated the earliest escapes in exquisite detail. Over 3-6 weeks, ultradeep sequencing revealed that the virus explored an extraordinary array of potential escape routes in the process of evading the earliest CD8 T-lymphocyte responses--using 454 sequencing, we identified over 50 variant forms of each targeted epitope during early immune escape, while only 2-7 variants were detected in the same samples via conventional sequencing. In contrast to the diversity seen within epitopes, non-epitope regions, including the Envelope V3 region, which was sequenced as a control in each subject, displayed very low levels of variation. In early infection, in the regions sequenced, the consensus forms did not have a fitness advantage large enough to trigger reversion to consensus amino acids in the absence of immune pressure. In one subject, a genetic bottleneck was observed, with extensive diversity at the second time point narrowing to two dominant escape forms by the third time point, all within two months of infection. Traces of immune escape were observed in the earliest samples, suggesting that immune pressure is present and effective earlier than previously reported; quantifying the loss rate of the founder virus suggests a direct role for CD8 T-lymphocyte responses in viral containment after peak viremia. Dramatic shifts in the frequencies of epitope variants during the first weeks of infection revealed a complex interplay between viral fitness and immune escape.
dc.format.extent e12303 - ?
dc.language eng
dc.language.iso en_US en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0012303
dc.subject Consensus Sequence
dc.subject Epitopes
dc.subject Evolution, Molecular
dc.subject Genome, Viral
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Immune Evasion
dc.subject Mutation
dc.subject Selection, Genetic
dc.subject Sequence Analysis, DNA
dc.subject Time Factors
dc.title Transmission of single HIV-1 genomes and dynamics of early immune escape revealed by ultra-deep sequencing.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-8-20 en_US
duke.description.endpage e12303 en_US
duke.description.issue 8 en_US
duke.description.startpage e12303 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20808830
pubs.issue 8
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Global Health Institute
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Immunology
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Medicine/Medicine, Duke Human Vaccine Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1932-6203

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