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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Functional consequences of human immunodeficiency virus escape from an HLA-B*13-restricted CD8
+
T-cell epitope in p1 gag protein
Journal of Virology, Volume 83, No. 2, Year 2009
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Description
The observed association between HLA-B*13 and control of human immunodeficiency virus type 1 (HIV-1) infection has been linked to the number of Gag-specific HLA-B*13-restricted cytotoxic T-cell (CTL) responses identified. To date, the Gag escape mutations described that result in an in vitro fitness cost to the virus have been located within structural protein p24 only. Here we investigated the hypothesis that CTL escape mutations within other regions of HIV Gag may also reduce viral fitness and contribute to immune control. We analyzed an HLA-B*13-restricted CTL response toward an epitope in p1 Gag, RQANFLGKI429-437 (RI9), where amino acid variation at Gag residues 436 and 437 is associated with HLA-B*13 expression. In this work, we assessed the impact of amino acid substitutions at these positions on CTL recognition and on HIV-1 fitness. We demonstrated that substitutions I437L and I437M largely abrogate CTL recognition and reduce viral fitness while variants K436R and I437V have only a marginal effect on recognition and fitness. Examination of the patterns of protein synthesis indicated that the loss of fitness in the I437L and I437M mutants is associated with the accumulation of unprocessed Gag precursors. A significant reduction in ribosomal frameshifting efficiency was observed with I437M, suggesting that this mechanism contributes to the observed reduced fitness of this virus. These studies illustrate the apparent trade-off available to the virus between evasion of CTL recognition in p1 Gag and the functional consequences for viral fitness. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Prado, Julia Garcia
United Kingdom, Oxford
Nuffield Department of Medicine
Honeyborne, Isobella
United Kingdom, Oxford
Nuffield Department of Medicine
Brierley, Ian
United Kingdom, Cambridge
University of Cambridge
Puertas, Maria C.
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Martínez-Picado, Javier
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
Nuffield Department of Medicine
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
Statistics
Citations: 58
Authors: 6
Affiliations: 6
Identifiers
Doi:
10.1128/JVI.01882-08
ISSN:
0022538X
Research Areas
Infectious Diseases