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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
HIV subtype influences HLA-B*07:02-associated HIV disease outcome
AIDS Research and Human Retroviruses, Volume 30, No. 5, Year 2014
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Description
Genetic polymorphisms within the MHC encoding region have the strongest impact on HIV disease progression of any in the human genome and provide important clues to the mechanisms of HIV immune control. Few analyses have been undertaken of HLA alleles associated with rapid disease progression. HLA-B*07:02 is an HLA class I molecule that is prevalent in most populations worldwide and that has previously been consistently linked to accelerated disease progression in B-clade infection. This study investigates the observation that HLA-B*07:02 is not associated with a high viral setpoint in C-clade infection. We examine the hypothesis that this clade-specific difference in association with disease outcome may be related to distinct targeting of CD8+ T cell epitopes. We observed that C-clade-infected individuals with HLA-B*07:02 target a broader range of Gag epitopes, and to higher magnitudes, than do individuals infected with B-clade infection. In particular, a novel p17-Gag (Gag22-30, RPGGKKHYM) epitope is targeted in >50% of HLA-B*07:02-positive C-clade-infected individuals but clade-specific differences in this epitope result in nonimmunogenicity in B-clade infection. Only the C-clade p24-Gag "GL9" (Gag355-363, GPSHKARVL) epitope-specific CD8+ T cell response out of 16 studied was associated with a low viral setpoint. Although this epitope was also targeted in B-clade infection, the escape mutant S357S is present at higher frequency in B-clade infection than in C-clade infection (70% versus 43% in HLA-B*07:02-negative subjects). These data support earlier studies suggesting that increased breadth of the Gag-specific CD8+ T cell response may contribute to improved HIV immune control irrespective of the particular HLA molecules expressed. © Copyright 2014, Mary Ann Liebert, Inc. 2014.
Authors & Co-Authors
Kløverpris, Henrik N.
United Kingdom, Oxford
University of Oxford
Denmark, Copenhagen
Københavns Universitet
South Africa, Durban
The Nelson R. Mandela Medical School
Adland, Emily
United Kingdom, Oxford
University of Oxford
Koyanagi, Madoka
Japan, Kumamoto
Kumamoto University
Stryhn, Anette
Denmark, Copenhagen
Københavns Universitet
Harndahl, Mikkel
Denmark, Copenhagen
Københavns Universitet
Matthews, Philippa C.
United Kingdom, Oxford
University of Oxford
Shapiro, Roger L.
United States, Boston
Harvard T.h. Chan School of Public Health
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Harvard University
United States, Chevy Chase
Howard Hughes Medical Institute
Ndung'u, Thumbi P.
South Africa, Durban
The Nelson R. Mandela Medical School
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Harvard University
Germany, Berlin
Max Planck Institute for Infection Biology
Brander, Christian
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Takiguchi, Masafumi
Japan, Kumamoto
Kumamoto University
Buus, Soren
Denmark, Copenhagen
Københavns Universitet
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Harvard University
Statistics
Citations: 25
Authors: 13
Affiliations: 11
Identifiers
Doi:
10.1089/aid.2013.0197
ISSN:
08892229
e-ISSN:
19318405
Research Areas
Genetics And Genomics
Infectious Diseases