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Journal of Virology, December 2007, p. 13125-13134, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01408-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Utility of Human Immunodeficiency Virus Type 1 Envelope as a T-Cell Immunogen{triangledown} ,{dagger}

Viv Peut and Stephen J. Kent*

Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia

Received 28 June 2007/ Accepted 12 September 2007

Human immunodeficiency virus (HIV)-specific CD8 T lymphocytes are important for the control of viremia, but the relative utility of responses to the various HIV proteins is controversial. Immune responses that force escape mutations that exact a significant fitness cost from the mutating virus would help slow progression to AIDS. The HIV envelope (Env) protein is subject to both humoral and cellular immune responses, suggesting that multiple rounds of mutation are needed to facilitate viral escape. The Gag protein, however, has recently been shown to elicit a more effective CD8 T-cell immune response in humans. We studied 30 pigtail macaques for their CD8 T-lymphocyte responses to HIV-1 Env and simian immunodeficiency virus (SIV) Gag following prime/boost vaccination and intrarectal challenge with simian-human immunodeficiency virus SHIVmn229. Eight CD8 Env-specific T-cell epitopes were identified and mapped in 10 animals. Animals that generated Env-specific CD8 T-cell responses had equivalent viral loads and only a modest advantage in retention of peripheral CD4 T lymphocytes compared to those animals without responses to Env. This contrasts with animals that generated CD8 T-cell responses to SIV Gag in the same trial, demonstrating superior control of viral load and a larger advantage in retention of peripheral CD4 T cells than Gag nonresponders. Mutational escape was common in Env but, in contrast to mutations in Gag, did not result in the rapid emergence of dominant escape motifs, suggesting modest selective pressure from Env-specific T cells. These results suggest that Env may have limited utility as a CD8 T-cell immunogen.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Parkville 3010, Australia. Phone: 61 3 83449939. Fax: 61 3 83443846. E-mail: skent{at}unimelb.edu.au

{triangledown} Published ahead of print on 26 September 2007.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, December 2007, p. 13125-13134, Vol. 81, No. 23
0022-538X/07/$08.00+0     doi:10.1128/JVI.01408-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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