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dc.contributor.authorTimm, J
dc.contributor.authorLauer, GM
dc.contributor.authorKavanagh, DG
dc.contributor.authorSheridan, I
dc.contributor.authorKim, AY
dc.contributor.authorLucas, M
dc.contributor.authorPillay, T
dc.contributor.authorOuchi, K
dc.contributor.authorReyor, LL
dc.contributor.authorSchulze Zur Wiesch, J
dc.contributor.authorGandhi, RT
dc.contributor.authorChung, RT
dc.contributor.authorBhardwaj, N
dc.contributor.authorKlenerman, P
dc.contributor.authorWalker, BD
dc.contributor.authorAllen, TM
dc.date.accessioned2020-08-13T11:06:05Z
dc.date.available2020-08-13T11:06:05Z
dc.date.issued2004-12-20
dc.identifier.issn0022-1007en
dc.identifier.pmid15611288 (pubmed)
dc.identifier.doi10.1084/jem.20041006en
dc.identifier.urihttp://hdl.handle.net/2436/623487
dc.description© 2004 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.20041006en
dc.description.abstractIn the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon γ enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.en
dc.description.sponsorshipJ. Timm and G.M. Lauer were funded by the Deutsche Forschungs Gemeinschaft (DFG TI-323/1-1 and DFG LA 1241/1-1). M. Lucas is funded by the EU (QLK2-CT-2002-01329), and P. Klenerman is funded by the Wellcome Trust. This work was funded by the National Institutes of Health (AI31563), the Doris Duke Charitable Foundation, and the Howard Hughes Medical Institute.en
dc.formatapplication/pdfen
dc.languageeng
dc.language.isoenen
dc.publisherRockefeller University Pressen
dc.relation.urlhttps://rupress.org/jem/article/200/12/1593/52226/CD8-Epitope-Escape-and-Reversion-in-Acute-HCVen
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.subjectHLA footprinten
dc.subjectprocessing mutationen
dc.subjectviral evolutionen
dc.subjectacute hepatitis Cen
dc.subjectCD8 escapeen
dc.titleCD8 epitope escape and reversion in acute HCV infectionen
dc.typeJournal articleen
dc.identifier.eissn1540-9538
dc.identifier.journalJournal of Experimental Medicineen
dc.date.updated2020-07-31T06:17:38Z
dc.contributor.institutionPartners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Bldg. 149, 13th St., Rm. 6618 B, Boston, MA 02114, USA.
pubs.place-of-publicationUnited States
dc.date.accepted2004-11-05
rioxxterms.funderDeutsche Forschungs Gemeinschaft, the EU, the Wellcome Trust, National Institutes of Health, the Doris Duke Charitable Foundation, and the Howard Hughes Medical Instituteen
rioxxterms.identifier.projectR01 AI031563en
rioxxterms.identifier.projectAI31563en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en
rioxxterms.licenseref.startdate2020-08-13en
dc.source.volume200
dc.source.issue12
dc.source.beginpage1593
dc.source.endpage1604
dc.description.versionPublished version
refterms.dateFCD2020-08-13T11:05:52Z
refterms.versionFCDVoR
refterms.dateFOA2020-08-13T11:06:06Z


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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