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

• 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
• Journal Title: Journal of Virology
• Volume: Volume 81, Number 15
• Publisher: American Society for Microbiology | 2007-08-01, Pages 8346-8351
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/JVI.00465-07
• Subjects: Biology, Virology; Health Sciences, Immunology; Biology, Microbiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Virology; VIROLOGY; T-LYMPHOCYTE ESCAPE; HIV-1 INFECTION; CELL RESPONSES; VIRAL LOAD; IN-VIVO; TRANSMISSION; HLA; AIDS; POLYMORPHISMS; ASSOCIATIONS

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.