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dc.contributor.authorLeslie, A
dc.contributor.authorKavanagh, D
dc.contributor.authorHoneyborne, I
dc.contributor.authorPfafferott, K
dc.contributor.authorEdwards, C
dc.contributor.authorPillay, T
dc.contributor.authorHilton, L
dc.contributor.authorThobakgale, C
dc.contributor.authorRamduth, D
dc.contributor.authorDraenert, R
dc.contributor.authorLe Gall, S
dc.contributor.authorLuzzi, G
dc.contributor.authorEdwards, A
dc.contributor.authorBrander, C
dc.contributor.authorSewell, AK
dc.contributor.authorMoore, S
dc.contributor.authorMullins, J
dc.contributor.authorMoore, C
dc.contributor.authorMallal, S
dc.contributor.authorBhardwaj, N
dc.contributor.authorYusim, K
dc.contributor.authorPhillips, R
dc.contributor.authorKlenerman, P
dc.contributor.authorKorber, B
dc.contributor.authorKiepiela, P
dc.contributor.authorWalker, B
dc.contributor.authorGoulder, P
dc.date.accessioned2020-08-13T11:21:26Z
dc.date.available2020-08-13T11:21:26Z
dc.date.issued2005-03-21
dc.identifier.citationLeslie, A., Kavanagh, D., Honeyborne, I. et al. (2005) Transmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLA, Journal of Experimental Medicine, 201 (6): 891–902.en
dc.identifier.issn0022-1007en
dc.identifier.pmid15781581 (pubmed)
dc.identifier.doi10.1084/jem.20041455en
dc.identifier.urihttp://hdl.handle.net/2436/623488
dc.description© 2005 The Authors. Published by Rockefeller University Press. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1084/jem.20041455en
dc.description.abstractHuman immunodeficiency virus (HIV)-1 amino acid sequence polymorphisms associated with expression of specific human histocompatibility leukocyte antigen (HLA) class I alleles suggest sites of cytotoxic T lymphocyte (CTL)-mediated selection pressure and immune escape. The associations most frequently observed are between expression of an HLA class I molecule and variation from the consensus sequence. However, a substantial number of sites have been identified in which particular HLA class I allele expression is associated with preservation of the consensus sequence. The mechanism behind this is so far unexplained. The current studies, focusing on two examples of "negatively associated" or apparently preserved epitopes, suggest an explanation for this phenomenon: negative associations can arise as a result of positive selection of an escape mutation, which is stable on transmission and therefore accumulates in the population to the point at which it defines the consensus sequence. Such negative associations may only be in evidence transiently, because the statistical power to detect them diminishes as the mutations accumulate. If an escape variant reaches fixation in the population, the epitope will be lost as a potential target to the immune system. These data help to explain how HIV is evolving at a population level. Understanding the direction of HIV evolution has important implications for vaccine development.en
dc.description.sponsorshipThis work was supported by the National Institutes of Health (contract N01-Al-15422 [“HLA typing and CTL epitope mapping to guide HIV vaccine development”] and AI46995-01A1), the Wellcome Trust (to P. Goulder and A. Leslie), the Elizabeth Glaser Pediatric AIDS Foundation (to P. Goulder), and the Doris Duke Charitable Foundation.en
dc.formatapplication/pdfen
dc.languageeng
dc.language.isoenen
dc.publisherRockefeller University Pressen
dc.relation.urlhttps://rupress.org/jem/article/201/6/891/52735/Transmission-and-accumulation-of-CTL-escapeen
dc.rightsLicence for published version: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subject.meshT-Lymphocytes, Cytotoxic
dc.subject.meshHumans
dc.subject.meshHIV-1
dc.subject.meshHIV Infections
dc.subject.meshAIDS Vaccines
dc.subject.meshHLA Antigens
dc.subject.meshEpitopes, T-Lymphocyte
dc.subject.meshEvolution, Molecular
dc.subject.meshGene Expression Regulation
dc.subject.meshAmino Acid Sequence
dc.subject.meshConsensus Sequence
dc.subject.meshMutation
dc.subject.meshPolymorphism, Genetic
dc.subject.meshAlleles
dc.subject.meshMolecular Sequence Data
dc.subject.meshAdult
dc.subject.meshChild
dc.subject.meshChild, Preschool
dc.subject.meshFemale
dc.subject.meshMale
dc.titleTransmission and accumulation of CTL escape variants drive negative associations between HIV polymorphisms and HLAen
dc.typeJournal articleen
dc.identifier.eissn1540-9538
dc.identifier.journalJournal of Experimental Medicineen
dc.date.updated2020-07-31T06:18:50Z
dc.contributor.institutionPeter Medawar Building, University of Oxford, Oxford OX13SY, UK.
pubs.place-of-publicationUnited States
dc.date.accepted2005-01-24
rioxxterms.funderNational Institutes of Health, the Wellcome Trust, the Elizabeth Glaser Pediatric AIDS Foundation, and the Doris Duke Charitable Foundationen
rioxxterms.identifier.projectAI46995-01A1en
rioxxterms.identifier.projectN01-AL-15422en
rioxxterms.identifier.projectR01 AI046995en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en
rioxxterms.licenseref.startdate2020-08-13en
dc.source.volume201
dc.source.issue6
dc.source.beginpage891
dc.source.endpage902
dc.description.versionPublished version
refterms.dateFCD2020-08-13T11:20:30Z
refterms.versionFCDVoR
refterms.dateFOA2020-08-13T11:21:26Z


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Licence for published version: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International
Except where otherwise noted, this item's license is described as Licence for published version: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International