Compensatory mutation partially restores fitness and delays reversion of escpe mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection

• Type of Material: Article
• Authors: Hayley Crawford, University of Oxford; Julia G. Prado, University of Oxford; Alasdair Leslie, University of Oxford; Stephane Hue, University of Oxford; Isobella Honeyborne, University of Oxford; Sharon Reddy, University of KwaZulu-Natal; Mary van der Stok, University of KwaZulu-Natal; Zenele Mncube, University of KwaZulu-Natal; Christian Brander, Massachusetts General Hospital; Christine Rousseau, University of Washington School of Medicine; James I. Mullins, University of Washington School of Medicine; Richard Kaslow, University of Alabama at Birmingham; Paul Goepfert, University of Alabama at Birmingham; Susan Allen, Emory University; Eric Hunter, Emory University; Joseph Mulenga, Zambia-Emory HIV Research Group (ZEHRG) and Zambia Blood Transfusion Service; Photini Kiepiela, University of KwaZulu-Natal; Bruce D. Walker, University of KwaZulu-Natal; Philip J. R. Goulder, University of Oxford
• Language: English
• Date: 2007-08-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2007, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.00465-07
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 81
• Issue: 15
• Start Page: 8346
• End Page: 8351
• Grant/Funding Information: This work was supported by the Wellcome Trust (P.J.R.G. and A.L.), NIH (contract N01-A1-15422 and 2RO1-AI-46995), the Department for International Development and Commonwealth Scholarship Commission (H.C.), the National Institutes of Health grant AI-64060 (E.H., P.G., and R.K.), the International AIDS Vaccine Initiative (S.A. and E.H.), and the Marie Curie Intra-European Fellowship (J.G.P.).
• Keywords: Virology; POLYMORPHISMS; T-LYMPHOCYTE ESCAPE; TRANSMISSION; AIDS; VIROLOGY; VIRAL LOAD; CELL RESPONSES; Life Sciences & Biomedicine; Science & Technology; HLA; ASSOCIATIONS; HIV-1 INFECTION; IN-VIVO
• Research Categories: Health Sciences, Immunology; Biology, Microbiology; Biology, Virology

Abstract

HLA-B*5703 is associated with effective immune control in human immunodeficiency virus type 1 (HIV-1) infection. Here we describe an escape mutation within the immunodominant HLA-B*5703-restricted epitope in chronic HIV-1 infection, KAFSPEVIPMF (Gag 162-172), and demonstrate that this mutation reduces viral replicative capacity. Reversion of this mutation following transmission to HLA-B*5703-negative recipients was delayed by the compensatory mutation S165N within the same epitope. These data may help explain the observed association between HLA-B*5703 and long-term control of viremia.