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Journal of Virology, October 2007, p. 11543-11548, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00779-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Antiretroviral Drug Therapy Alters the Profile of Human Immunodeficiency Virus Type 1-Specific T-Cell Responses and Shifts the Immunodominant Cytotoxic T-Lymphocyte Response from Gag to Pol{triangledown}

A. C. Karlsson,1,2* J. M. Chapman,3 B. D. Heiken,1 R. Hoh,4 E. G. Kallas,5 J. N. Martin,4 F. M. Hecht,3 S. G. Deeks,3,{dagger} and D. F. Nixon3,{dagger}

Gladstone Institute of Virology and Immunology, University of California, San Francisco, California 94141,1 The Swedish Institute for Infectious Disease Control and Karolinska Institutet, 171 82 Solna, Sweden,2 Division of Experimental Medicine, Department of Medicine, University of California, San Francisco,3 Positive Health Program, San Francisco General Hospital, San Francisco, California 94110,4 Federal University of São Paulo, Sao Paulo, Brazil5

Received 11 April 2007/ Accepted 20 July 2007

Antiretroviral drug therapy and cytotoxic T lymphocytes (CTL) both exert selective pressures on human immunodeficiency virus type 1, which influence viral evolution. Compared to chronically infected, antiretroviral-untreated patients, most chronically infected, treated patients with detectable viremia lack a cellular immune response against the Gag 77-85(SL9) epitope but show a new immunodominant response against an epitope in protease PR 76-84. Hence, mutations induced by antiretroviral therapy likely alter the profile of epitopes presented to T cells and thus the direction of the response. The consequences of dual pressures from treatment and CTL need to be considered in monitoring of drug therapy.

* Corresponding author. Mailing address: Karolinska Institutet and The Swedish Institute for Infectious Disease Control (SMI), Department of Virology, Immunology, and Vaccinology, 171 82 Solna, Sweden. Phone: 46 8 457 26 19. Fax: 46 8 33 72 72. E-mail: annika.karlsson{at}smi.ki.se

{triangledown} Published ahead of print on 1 August 2007.

{dagger} S.G.D. and D.F.N. made equal contributions to this study.

Journal of Virology, October 2007, p. 11543-11548, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00779-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.





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