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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Adaptation of HIV-1 to human leukocyte antigen class I
Nature, Volume 458, No. 7238, Year 2009
Notification
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Description
The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8 + T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8 + T-cell recognition. Here we analysed viral sequences and HLA alleles from 2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8 + T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV. © 2009 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
Kawashima, Yuka
Japan, Kumamoto
Kumamoto University
Pfafferott, Katja J.
United Kingdom, Oxford
Nuffield Department of Medicine
Australia, Perth
Murdoch University
Frater, John
United Kingdom, Oxford
Nuffield Department of Medicine
Matthews, Philippa C.
United Kingdom, Oxford
Nuffield Department of Medicine
Payne, Rebecca P.
United Kingdom, Oxford
Nuffield Department of Medicine
Addo, Marylyn Martina
United States, Boston
Massachusetts General Hospital
Gatanaga, Hiroyuki
Japan, Kumamoto
Kumamoto University
Japan, Tokyo
National Center for Global Health and Medicine
Fujiwara, Mamoru
Japan, Kumamoto
Kumamoto University
Hachiya, Atsuko
Japan, Kumamoto
Kumamoto University
Japan, Tokyo
National Center for Global Health and Medicine
Koizumi, Hirokazu
Japan, Kumamoto
Kumamoto University
Kuse, Nozomi
Japan, Kumamoto
Kumamoto University
Oka, Shinichi
Japan, Kumamoto
Kumamoto University
Japan, Tokyo
National Center for Global Health and Medicine
Duda, Anna
United Kingdom, Oxford
Nuffield Department of Medicine
Prendergast, Andrew J.
United Kingdom, Oxford
Nuffield Department of Medicine
Crawford, Hayley
United Kingdom, Oxford
Nuffield Department of Medicine
Leslie, Alasdair J.
United States, Boston
Massachusetts General Hospital
Brumme, Zabrina L.
United States, Boston
Massachusetts General Hospital
Brumme, Chanson J.
United States, Boston
Massachusetts General Hospital
Allen, Todd M.
United States, Boston
Massachusetts General Hospital
Brander, Christian
United States, Boston
Massachusetts General Hospital
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Kaslow, Richard A.
United States, Birmingham
The University of Alabama at Birmingham
Tang, James J.
United States, Birmingham
The University of Alabama at Birmingham
Hunter, Eric
United States, Atlanta
Emory University
Allen, Susan A.
Zambia, Lusaka
Zambia-emory Hiv Research Project
Mulenga, Joseph
Zambia, Lusaka
Zambia-emory Hiv Research Project
Branch, Songee L.
Jamaica, Kingston
The University of the West Indies
Roach, Timothy C.
Jamaica, Kingston
The University of the West Indies
John, Mina
Australia, Perth
Murdoch University
Mallal, Simon Alexander
Australia, Perth
Murdoch University
Ogwu, Anthony C.
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Shapiro, Roger L.
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Prado, Julia Garcia
United Kingdom, Oxford
Nuffield Department of Medicine
Fidler, Sarah J.
United Kingdom, London
St Mary's Hospital
Weber, Jonathan N.
United Kingdom, London
St Mary's Hospital
Pybus, Oliver George
United Kingdom, Oxford
University of Oxford
Klenerman, Paul
United Kingdom, Oxford
Nuffield Department of Medicine
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
Phillips, Rodney E.
United Kingdom, Oxford
Nuffield Department of Medicine
Heckerman, David E.
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Harrigan, P. Richard
United States, Redmond
Microsoft Research
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
South Africa, Durban
University of Kwazulu-natal
United States, Chevy Chase
Howard Hughes Medical Institute
Takiguchi, Masafumi
Japan, Kumamoto
Kumamoto University
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
Nuffield Department of Medicine
Australia, Perth
Murdoch University
South Africa, Durban
University of Kwazulu-natal
Statistics
Citations: 479
Authors: 43
Affiliations: 17
Identifiers
Doi:
10.1038/nature07746
ISSN:
00280836
e-ISSN:
14764687
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study