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dc.contributor.authorStreeck, Hendrik
dc.contributor.authorLi, Bin
dc.contributor.authorPoon, Art F. Y.
dc.contributor.authorSchneidewind, Anne
dc.contributor.authorGladden, Adrianne D.
dc.contributor.authorPower, Karen A.
dc.contributor.authorDaskalakis, Demetre
dc.contributor.authorBazner, Suzane
dc.contributor.authorZuniga, Rosario
dc.contributor.authorBrander, Christian
dc.contributor.authorRosenberg, Eric Scott
dc.contributor.authorFrost, Simon D. W.
dc.contributor.authorAltfeld, Marcus
dc.contributor.authorAllen, Todd
dc.date.accessioned2011-03-20T20:29:48Z
dc.date.issued2008
dc.identifier.citationStreeck, Hendrik, Bin Li, Art F.Y. Poon, Arne Schneidewind, Adrianne D. Gladden, Karen A. Power, Demetre Daskalakis, Suzane Bazner, Rosario Zuniga, Christian Brander, Eric S. Rosenberg, Simon D.W. Frost, Marcus Altfeld, and Todd M. Allen. 2008. Immune-driven recombination and loss of control after HIV superinfection. The Journal of Experimental Medicine 205(8): 1789-1796.en_US
dc.identifier.issn0022-1007en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4745744
dc.description.abstractAfter acute HIV infection, CD8^{+} T cells are able to control viral replication to a set point. This control is often lost after superinfection, although the mechanism behind this remains unclear. In this study, we illustrate in an HLA-B27^{+} subject that loss of viral control after HIV superinfection coincides with rapid recombination events within two narrow regions of Gag and Env. Screening for CD8^{+} T cell responses revealed that each of these recombination sites (∼50 aa) encompassed distinct regions containing two immunodominant CD8 epitopes (B27-KK10 in Gag and Cw1-CL9 in Env). Viral escape and the subsequent development of variant-specific de novo CD8^{+} T cell responses against both epitopes were illustrative of the significant immune selection pressures exerted by both responses. Comprehensive analysis of the kinetics of CD8 responses and viral evolution indicated that the recombination events quickly facilitated viral escape from both dominant WT- and variant-specific responses. These data suggest that the ability of a superinfecting strain of HIV to overcome preexisting immune control may be related to its ability to rapidly recombine in critical regions under immune selection pressure. These data also support a role for cellular immune pressures in driving the selection of new recombinant forms of HIV.en_US
dc.language.isoen_USen_US
dc.publisherThe Rockefeller University Pressen_US
dc.relation.isversionofdoi:10.1084/jem.20080281en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525594/pdf/en_US
dash.licenseLAA
dc.subjectT-Lymphocyte Responseen_US
dc.subjectCTL Escape Mutationen_US
dc.subjectCell Responsesen_US
dc.subjectVirusen_US
dc.subjectInfectionen_US
dc.subjectReplicationen_US
dc.subjectViremiaen_US
dc.subjectGagen_US
dc.subjectTransmissionen_US
dc.subjectProgressionen_US
dc.titleImmune-Driven Recombination and Loss of Control after HIV Superinfectionen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalThe Journal of Experimental Medicineen_US
dash.depositing.authorAllen, Todd
dc.date.available2011-03-20T20:29:48Z
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dash.affiliation.otherHMS^Medicine-Massachusetts General Hospitalen_US
dc.identifier.doi10.1084/jem.20080281*
dash.contributor.affiliatedRosenberg, Eric
dash.contributor.affiliatedStreeck, Hendrik
dash.contributor.affiliatedAltfeld, Marcus
dash.contributor.affiliatedBrander, Christian
dash.contributor.affiliatedAllen, Todd


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