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dc.contributor.authorRead, Elizabeth L.
dc.contributor.authorTovo-Dwyer, Allison A.
dc.contributor.authorChakraborty, Arup K
dc.date.accessioned2013-05-07T15:58:38Z
dc.date.available2013-05-07T15:58:38Z
dc.date.issued2012-10
dc.date.submitted2012-04
dc.identifier.issn0027-8424
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/78837
dc.description.abstractBlood plasma viral loads and the time to progress to AIDS differ widely among untreated HIV-infected humans. Although people with certain HLA (HLA-I) alleles are more likely to control HIV infections without therapy, the majority of such untreated individuals exhibit high viral loads and progress to AIDS. Stochastic effects are considered unimportant for evolutionary dynamics in HIV-infected people when viral load is high or when selective forces strongly drive mutation. We describe a computational study of host–pathogen interaction demonstrating that stochastic effects can have a profound influence on disease dynamics, even in cases of high viral load and strong selective pressure. These stochastic effects are pronounced when the virus must traverse a fitness “barrier” in sequence space to escape the host’s cytotoxic T-lymphocyte (CTL) response, as often occurs when a fitness defect imposed by a CTL-driven mutation must be compensated for by other mutations. These “barrier-crossing” events are infrequent and stochastic, resulting in divergent disease outcomes in genetically identical individuals infected by the same viral strain. Our results reveal how genetic determinants of the CTL response control the probability with which an individual is able to control HIV infection indefinitely, and thus provide clues for vaccine design.en_US
dc.description.sponsorshipJane Coffins Childs Foundationen_US
dc.description.sponsorshipMassachusetts Institute of Technology. Ragon Institute of MGH, MIT and Harvarden_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Director’s Pioneer Award)en_US
dc.language.isoen_US
dc.publisherNational Academy of Sciences (U.S.)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1206940109en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleStochastic effects are important in intrahost HIV evolution even when viral loads are highen_US
dc.typeArticleen_US
dc.identifier.citationRead, E. L., A. A. Tovo-Dwyer, and A. K. Chakraborty. “Stochastic Effects Are Important in Intrahost HIV Evolution Even When Viral Loads Are High.” Proceedings of the National Academy of Sciences 109.48 (2012): 19727–19732.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Medical Engineering & Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.departmentRagon Institute of MGH, MIT and Harvarden_US
dc.contributor.mitauthorChakraborty, Arup K.
dc.contributor.mitauthorRead, Elizabeth L.
dc.contributor.mitauthorTovo-Dwyer, Allison A.
dc.relation.journalProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsRead, E. L.; Tovo-Dwyer, A. A.; Chakraborty, A. K.en
dc.identifier.orcidhttps://orcid.org/0000-0003-1268-9602
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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