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Journal of Virology, April 2009, p. 3407-3412, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02459-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

HLA-Associated Viral Mutations Are Common in Human Immunodeficiency Virus Type 1 Elite Controllers{triangledown}

Toshiyuki Miura,1,2,3* Chanson J. Brumme,1 Mark A. Brockman,1,2 Zabrina L. Brumme,1,2 Florencia Pereyra,1,2 Brian L. Block,2 Alicja Trocha,1,3 Mina John,4 Simon Mallal,4 P. Richard Harrigan,5,6 and Bruce D. Walker1,2,3*

Ragon Institute (formerly Partners AIDS Research Center), Massachusetts General Hospital, Charlestown, Massachusetts 02129,1 Division of AIDS, Harvard Medical School, Boston, Massachusetts 02115,2 Howard Hughes Medical Institute, Chevy Chase, Maryland 20815,3 Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia,4 British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada,5 Division of AIDS, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada6

Received 1 December 2008/ Accepted 9 January 2009

Elite controllers (EC) of human immunodeficiency virus type 1 (HIV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8+ T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC, compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HIV-1 infection.

* Corresponding author. Present address of Toshiyuki Miura: Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan. Phone: 81-3-5449-5338. Fax: 81-3-5449-5427. E-mail: miura523{at}hotmail.com. Mailing address for Bruce D. Walker: Room 5212, Ragon Institute, Massachusetts General Hospital, 149 13th St., Charlestown, MA 02129. Phone: (617) 724-8332. Fax: (617) 726-4691. E-mail: bwalker{at}partners.org

{triangledown} Published ahead of print on 19 January 2009.

Journal of Virology, April 2009, p. 3407-3412, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02459-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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