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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression
Journal of Virology, Volume 81, No. 12, Year 2007
Notification
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Description
The possession of some HLA class I molecules is associated with delayed progression to AIDS. The mechanism behind this beneficial effect is unclear. We tested the idea that cytotoxic T-cell responses restricted by advantageous HLA class I molecules impose stronger selection pressures than those restricted by other HLA class I alleles. As a measure of the selection pressure imposed by HLA class I alleles, we determined the extent of HLA class I-associated epitope variation in a cohort of European human immunodeficiency virus (HIV)-positive individuals (n = 84). We validated our findings in a second, distinct cohort of African patients (n = 516). We found that key HIV epitopes restricted by advantageous HLA molecules (B27, B57, and B51 in European patients and B5703, B5801, and B8101 in African patients) were more frequently mutated in individuals bearing the restricting HLA than in those who lacked the restricting HLA class I molecule. HLA alleles associated with clinical benefit restricted certain epitopes for which the consensus peptides were frequently recognized by the immune response despite the circulating virus's being highly polymorphic. We found a significant inverse correlation between the HLA-associated hazard of disease progression and the mean HLA-associated prevalence of mutations within epitopes (P = 0.028; R2 = 0.34). We conclude that beneficial HLA class I alleles impose strong selection at key epitopes. This is revealed by the frequent association between effective T-cell responses and circulating viral escape mutants and the rarity of these variants in patients who lack these favorable HLA class I molecules, suggesting a significant pressure to revert. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC1900110/bin/jvirol_81_12_6742__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC1900110/bin/jvirol_81_12_6742__JV_Supp_resubmit.zip
Authors & Co-Authors
Frater, John
United Kingdom, Oxford
Nuffield Department of Medicine
Brown, Helen L.
United Kingdom, Oxford
Nuffield Department of Medicine
Oxenius, Annette
Switzerland, Zurich
Eth Zürich
Günthard, Hüldrych Fritz
Switzerland, Zurich
Universitatsspital Zurich
Hirschel, B. J.
Switzerland, Geneva
University Hospital
Robinson, Nicola
United Kingdom, Oxford
Nuffield Department of Medicine
Leslie, Alasdair J.
United Kingdom, Oxford
Nuffield Department of Medicine
Payne, Rebecca P.
United Kingdom, Oxford
Nuffield Department of Medicine
Crawford, Hayley
United Kingdom, Oxford
Nuffield Department of Medicine
Prendergast, Andrew J.
United Kingdom, Oxford
Nuffield Department of Medicine
Brander, Christian
United States, Boston
Massachusetts General Hospital
Kiepiela, Photini
South Africa, Durban
University of Kwazulu-natal
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
South Africa, Durban
University of Kwazulu-natal
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
Nuffield Department of Medicine
United States, Boston
Massachusetts General Hospital
South Africa, Durban
University of Kwazulu-natal
McLean, Angela R.
United Kingdom, Oxford
University of Oxford
Phillips, Rodney E.
United Kingdom, Oxford
Nuffield Department of Medicine
Battegay, Manuel
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Bernasconi, Enos
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Böni, Jürg
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Bucher, Heiner C.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Bürgisser, Ph
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Cattacin, Sandro
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Cavassini, Matthias L.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Dubs, Rolf W.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Egger, Matthias
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Elzi, Luigia
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Erb, Peter
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Fischer, Marek
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Flepp, Markus J.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Fontana, Adriano
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Francioli, Patrick B.
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Furrer, Hansjakob
Unknown Affiliation
Gorgievski, Meri
Unknown Affiliation
Günthard, Huldrych F.
Unknown Affiliation
Hirsch, Hans H.
Unknown Affiliation
Hirschel, B.
Unknown Affiliation
Hösli, Irene Mathilde
Unknown Affiliation
Kahlert, Christian R.
Unknown Affiliation
Kaiser, Laurent K.
Unknown Affiliation
Karrer, Urs
Unknown Affiliation
Kind, Christian H.
Unknown Affiliation
Klimkait, Thomas
Unknown Affiliation
Ledergerber, Bruno
Unknown Affiliation
Martinetti, Gladys
Unknown Affiliation
Martinez, Begogna
Unknown Affiliation
Müller, Nicolas J.
Unknown Affiliation
Nadal, David
Unknown Affiliation
Opravil, Milos
Unknown Affiliation
Paccaud, Fred Michel
Unknown Affiliation
Pantaleo, Giuseppe P.
Unknown Affiliation
Rickenbach, Martin
Unknown Affiliation
Rudin, Christoph
Unknown Affiliation
Schmid, Patrick
Unknown Affiliation
Schültze, Detlev
Unknown Affiliation
Schüpbach, Jörg Rg
Unknown Affiliation
Speck, Roberto F.
Unknown Affiliation
Taffé, Patrick
Unknown Affiliation
Tarr, Philip E.
Unknown Affiliation
Telenti, Amalio
Unknown Affiliation
Trkola, Alexandra
Unknown Affiliation
Vernazza, Pietro Luigi
Unknown Affiliation
Weber, Rainer
Unknown Affiliation
Yerly, Sabine T.B.D.
Unknown Affiliation
Statistics
Citations: 118
Authors: 63
Affiliations: 10
Identifiers
Doi:
10.1128/JVI.00022-07
ISSN:
0022538X
Research Areas
Environmental
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study