This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01096-07v1 82/1/495    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cao, J. Articles by McElrath, M. J. Search for Related Content PubMed PubMed Citation Articles by Cao, J. Articles by McElrath, M. J.

 Previous Article  |  Next Article 

Journal of Virology, January 2008, p. 495-502, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01096-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Novel Cytotoxic T-Lymphocyte Escape Mutation by a Three-Amino-Acid Insertion in the Human Immunodeficiency Virus Type 1 p6^Pol and p6^Gag Late Domain Associated with Drug Resistance

Jianhong Cao,^1,2, John McNevin,¹ Matthew McSweyn,¹ Yi Liu,⁴ James I. Mullins,^2,3,4 and M. Juliana McElrath^1,2,3*

Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center,¹ Department of Medicine,² Department of Laboratory Medicine,³ Department of Microbiology, University of Washington, Seattle, Washington⁴

Received 21 May 2007/ Accepted 4 October 2007

Cytolytic T lymphocytes (CTL) play a major role in controlling human immunodeficiency virus type 1 (HIV-1) infection. To evade immune pressure, HIV-1 is selected at targeted CTL epitopes, which may consequentially alter viral replication fitness. In our longitudinal investigations of the interplay between T-cell immunity and viral evolution following acute HIV-1 infection, we observed in a treatment-naïve patient the emergence of highly avid, gamma interferon-secreting, CD8⁺ CTL recognizing an HLA-Cw*0102-restricted epitope, NSPTRREL (NL8). This epitope lies in the p6^Pol protein, located in the transframe region of the Gag-Pol polyprotein. Over the course of infection, an unusual viral escape mutation arose within the p6^Pol epitope through insertion of a 3-amino-acid repeat, NSPT(SPT)RREL, with a concomitant insertion in the p6^Gag late domain, PTAPP(APP). Interestingly, this p6^Pol insertion mutation is often selected in viruses with the emergence of antiretroviral drug resistance, while the p6^Gag late-domain PTAPP motif binds Tsg101 to permit viral budding. These results are the first to demonstrate viral evasion of immune pressure by amino acid insertions. Moreover, this escape mutation represents a novel mechanism whereby HIV-1 can alter its sequence within both the Gag and Pol proteins with potential functional consequences for viral replication and budding.

Published ahead of print on 17 October 2007.

Present address: Immune Monitoring Lab, Fred Hutchinson Cancer Research Center, Seattle, WA.

This article has been cited by other articles:

• Miura, T., Brockman, M. A., Brumme, C. J., Brumme, Z. L., Carlson, J. M., Pereyra, F., Trocha, A., Addo, M. M., Block, B. L., Rothchild, A. C., Baker, B. M., Flynn, T., Schneidewind, A., Li, B., Wang, Y. E., Heckerman, D., Allen, T. M., Walker, B. D. (2008). Genetic Characterization of Human Immunodeficiency Virus Type 1 in Elite Controllers: Lack of Gross Genetic Defects or Common Amino Acid Changes. J. Virol. 82: 8422-8430 [Abstract] [Full Text]