Abstract |
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.
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Authors | Jianhong Cao, John McNevin, Matthew McSweyn, Yi Liu, James I Mullins, M Juliana McElrath |
Journal | Journal of virology
(J Virol)
Vol. 82
Issue 1
Pg. 495-502
(Jan 2008)
ISSN: 1098-5514 [Electronic] United States |
PMID | 17942528
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Anti-HIV Agents
- Epitopes, T-Lymphocyte
- gag Gene Products, Human Immunodeficiency Virus
- p6 gag protein, Human immunodeficiency virus 1
- pol Gene Products, Human Immunodeficiency Virus
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Topics |
- Anti-HIV Agents
(pharmacology)
- Epitopes, T-Lymphocyte
(genetics, immunology)
- HIV Infections
(immunology, virology)
- HIV-1
(drug effects, genetics, immunology)
- Humans
- Longitudinal Studies
- Mutagenesis, Insertional
- Protein Structure, Tertiary
- T-Lymphocytes, Cytotoxic
(immunology)
- gag Gene Products, Human Immunodeficiency Virus
(chemistry, genetics, immunology)
- pol Gene Products, Human Immunodeficiency Virus
(chemistry, genetics, immunology)
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