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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Differential clade-specific HLA-B*3501 association with HIV-1 disease outcome is linked to immunogenicity of a single gag epitope
Journal of Virology, Volume 86, No. 23, Year 2012
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Description
The strongest genetic influence on immune control in HIV-1 infection is the HLA class I genotype. Rapid disease progression in B-clade infection has been linked to HLA-B*35 expression, in particular to the less common HLA-B*3502 and HLA-B*3503 subtypes but also to the most prevalent subtype, HLA-B*3501. In these studies we first demonstrated that whereas HLA-B*3501 is associated with a high viral set point in two further B-clade-infected cohorts, in Japan and Mexico, this association does not hold in two large C-clade-infected African cohorts. We tested the hypothesis that clade-specific differences in HLA associations with disease outcomes may be related to distinct targeting of critical CD8+ T-cell epitopes. We observed that only one epitope was significantly targeted differentially, namely, the Gag-specific epitope NPPIPVGDIY (NY10, Gag positions 253 to 262) (P=2× 10-5). In common with two other HLA-B*3501-restricted epitopes, in Gag and Nef, that were not targeted differentially, a response toward NY10 was associated with a significantly lower viral set point. Nonimmunogenicity of NY10 in B-clade-infected subjects derives from the Gag-D260E polymorphism present in~90% of B-clade sequences, which critically reduces recognition of the Gag NY10 epitope. These data suggest that in spite of any inherent HLA-linked T-cell receptor repertoire differences that may exist, maximizing the breadth of the Gag-specific CD8+ T-cell response, by the addition of even a single epitope, may be of overriding importance in achieving immune control of HIV infection. This distinction is of direct relevance to development of vaccines designed to optimize the anti-HIV CD8+ T-cell response in all individuals, irrespective of HLA type. © 2012, American Society for Microbiology.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3497693/bin/supp_86_23_12643__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3497693/bin/JVI.01381-12_zjv999096841so1.pdf
Authors & Co-Authors
Matthews, Philippa C.
United Kingdom, Oxford
University of Oxford
Koyanagi, Madoka
Japan, Kumamoto
Kumamoto University
Kløverpris, Henrik N.
United Kingdom, Oxford
University of Oxford
Harndahl, Mikkel
Denmark, Copenhagen
Københavns Universitet
Stryhn, Anette
Denmark, Copenhagen
Københavns Universitet
Akahoshi, Tomohiro
Japan, Kumamoto
Kumamoto University
Gatanaga, Hiroyuki
Japan, Kumamoto
Kumamoto University
Japan, Tokyo
National Center for Global Health and Medicine
Oka, Shinichi
Japan, Kumamoto
Kumamoto University
Japan, Tokyo
National Center for Global Health and Medicine
Molina, Claudia J.
United Kingdom, Oxford
University of Oxford
Ponce, Humberto Valenzuela
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Ávila-Ríos, Santiago
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Cole, David K.
United Kingdom, Cardiff
Cardiff University School of Medicine
Carlson, Jonathan M.
United States, Redmond
Microsoft Research
Payne, Rebecca P.
United Kingdom, Oxford
University of Oxford
Ogwu, Anthony C.
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Bere, Alfred
United States, Atlanta
Emory University
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
Gounder, Kamini
South Africa, Durban
University of Kwazulu-natal
Chen, Fabian
United Kingdom, Reading
Royal Berkshire Hospital
Riddell, Lynn A.
United Kingdom, Northampton
Northampton General Hospital
Luzzi, Graz A.
United Kingdom, High Wycombe
Wycombe Hospital
Shapiro, Roger L.
United States, Boston
Harvard T.h. Chan School of Public Health
Brander, Christian
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
Sewell, Andrew Kelvin
United Kingdom, Cardiff
Cardiff University School of Medicine
Teran, Gustavo Reyes
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Heckerman, David E.
United States, Redmond
Microsoft Research
Hunter, Eric
United States, Atlanta
Emory University
Buus, Soren
Denmark, Copenhagen
Københavns Universitet
Takiguchi, Masafumi
Japan, Kumamoto
Kumamoto University
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
Statistics
Citations: 55
Authors: 31
Affiliations: 17
Identifiers
Doi:
10.1128/JVI.01381-12
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cohort Study