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Journal of Virology, August 2007, p. 8346-8351, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00465-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Compensatory Mutation Partially Restores Fitness and Delays Reversion of Escape Mutation within the Immunodominant HLA-B*5703-Restricted Gag Epitope in Chronic Human Immunodeficiency Virus Type 1 Infection{triangledown}

Hayley Crawford,1 Julia G. Prado,1 Alasdair Leslie,1 Stéphane Hué,1 Isobella Honeyborne,1 Sharon Reddy,2 Mary van der Stok,2 Zenele Mncube,2 Christian Brander,3 Christine Rousseau,4 James I. Mullins,4 Richard Kaslow,5 Paul Goepfert,5 Susan Allen,6 Eric Hunter,7 Joseph Mulenga,6 Photini Kiepiela,2 Bruce D. Walker,2,3,8 and Philip J. R. Goulder1,2,3*

Department of Pediatrics, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Rd., Oxford OX1 3SY, United Kingdom,1 HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban 4013, South Africa,2 Partners AIDS Research Center, Massachusetts General Hospital, 13th St., Bldg. 149, Charlestown, Boston, Massachusetts 02129,3 Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195-8070,4 University of Alabama at Birmingham, Birmingham, Alabama 35294-0022,5 Zambia-Emory HIV Research Group (ZEHRG) and Zambia Blood Transfusion Service, Lusaka, Zambia,6 Emory Vaccine Center, Emory University, Atlanta, Georgia 30329,7 Howard Hughes Medical Institute, Chevy Chase, Maryland 208158

Received 5 March 2007/ Accepted 8 May 2007

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.

* Corresponding author. Mailing address: Department of Pediatrics, University of Oxford, Peter Medawar Building for Pathogen Research, South Parks Rd., Oxford OX1 3SY, United Kingdom. Phone: 44 1865 281884. Fax: 44 1865 281236. E-mail: philip.goulder{at}ndm.ox.ac.uk

{triangledown} Published ahead of print on 16 May 2007.

Journal of Virology, August 2007, p. 8346-8351, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00465-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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