Adaptation of hiv-1 to human leukocyte antigen class i

ABSTRACT 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

infection1. 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

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subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS IMMUNE TARGETING OF HIV-1 RESERVOIR CELLS: A PATH TO ELIMINATION STRATEGIES AND CURE Article

09 February 2024 COMMON EVOLUTIONARY FEATURES OF THE ENVELOPE GLYCOPROTEIN OF HIV-1 IN PATIENTS BELONGING TO A TRANSMISSION CHAIN Article Open access 07 October 2020 PHENOTYPIC SIGNATURES OF

IMMUNE SELECTION IN HIV-1 RESERVOIR CELLS Article Open access 04 January 2023 ACCESSION CODES DATA DEPOSITS Accession numbers for newly determined viral sequences are included in

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AI067073 (B.D.W.), R01AI64060 (E.H.)), the Wellcome Trust (P.G., P.K.), the UK Medical Research Council (J.F., A.P. and P.M.), and the Mark and Lisa Schwartz Foundation, the Ministry of

Health, Labour and Welfare (Health and Labour HIV/AIDS Research Grants 012), the NIHR Biomedical Research Centre Programme and the Ministry of Education, Science, Sports and Culture (number

18390141), Japan (M.T.). P.G. is an Elizabeth Glaser Pediatric AIDS Foundation Scientist; J.G.P. is a Marie Curie Fellow (contract number IEF-041811). The authors are also grateful to A.

McLean and H. Fryer for discussions of the manuscript. AUTHOR CONTRIBUTIONS Y.K., K.P., J.F. and P. M. undertook much of the experimental work and data analysis, and contributed equally.

M.T. and P.G. undertook much of the project conception, planning, supervision, analysis and writing of the manuscript, and contributed equally. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Divisions of Viral Immunology and,, Yuka Kawashima, Mamoru Fujiwara, Atsuko Hachiya, Hirokazu Koizumi, Nozomi Kuse & Masafumi Takiguchi * Infectious Disease, Center for AIDS Research,

Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan , Hiroyuki Gatanaga & Shinichi Oka * Department of Paediatrics,, Katja Pfafferott, Philippa Matthews, Rebecca Payne, Andrew

Prendergast, Hayley Crawford, Alasdair Leslie, Julia G. Prado & Philip Goulder * Nuffield Department of Clinical Medicine and,, John Frater, Anna Duda, Paul Klenerman & Rodney

Phillips * The James Martin 21st Century School, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK , John Frater, Anna Duda, Paul Klenerman & Rodney

Phillips * Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Western Australia 6000, Australia Katja Pfafferott, Mina John, Simon Mallal 

& Philip Goulder * Partners AIDS Research Center, Massachusetts General Hospital, 13th Street, Building 149, Charlestown, Boston, Massachusetts 02129, USA , Marylyn Addo, Zabrina Brumme,

 Chanson Brumme, Todd Allen, Christian Brander & Bruce D. Walker * AIDS Clinical Center, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan ,

Hiroyuki Gatanaga, Atsuko Hachiya & Shinichi Oka * Fundació IrsiCaixa-HIVACAT, Hospital Germans Trias i Pujol, Badalona and Institucio Catalana de Recerca i Estudis Avancats (ICREA),

Barcelona 08916, Spain Christian Brander * University of Alabama at Birmingham, Birmingham, Alabama 35294, USA , Richard Kaslow & James Tang * Emory University Vaccine Center and Yerkes

National Primate Research Center, Atlanta, Georgia 30329, USA , Eric Hunter * Zambia Emory HIV Research Project, and the Zambia Blood Transfusion Service, Lusaka, Zambia Susan Allen & 

Joseph Mulenga * Ladymeade Reference Unit, University of West Indies, Bridgetown BB11156, Barbados Songee Branch & Tim Roach * Botswana-Harvard School of Public Health AIDS Initiative

Partnership, Gaborone, Botswana Anthony Ogwu & Roger Shapiro * Division of Medicine, Wright Fleming Institute, Imperial College, St Mary’s Hospital, Norfolk Place, Paddington, London W2

1PG, UK, Sarah Fidler & Jonathan Weber * Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3SY, UK, Oliver G. Pybus * HIV Pathogenesis Programme, The Doris Duke

Medical Research Institute, University of KwaZulu-Natal, Durban 4013, South Africa Thumbi Ndung’u, Bruce D. Walker & Philip Goulder * Miscrosoft Research, One Microsoft Way, Redmond,

Washington 9805, USA , P. Richard Harrigan * BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia V6Z 1Y6, Canada , David Heckerman * Howard Hughes Medical Institute, Chevy

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Kawashima, Y., Pfafferott, K., Frater, J. _et al._ Adaptation of HIV-1 to human leukocyte antigen class I. _Nature_ 458, 641–645 (2009). https://doi.org/10.1038/nature07746 Download citation

* Received: 13 October 2008 * Accepted: 22 December 2008 * Published: 25 February 2009 * Issue Date: 02 April 2009 * DOI: https://doi.org/10.1038/nature07746 SHARE THIS ARTICLE Anyone you

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