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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Differential escape patterns within the dominant HLA-B*57:03-restricted HIV gag epitope reflect distinct clade-specific functional constraints
Journal of Virology, Volume 88, No. 9, Year 2014
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Description
HLA-B*57:01 and HLA-B*57:03, the most prevalent HLA-B*57 subtypes in Caucasian and African populations, respectively, are the HLA alleles most protective against HIV disease progression. Understanding the mechanisms underlying this immune control is of critical importance, yet they remain unclear. Unexplained differences are observed in the impact of the dominant cytotoxic T lymphocyte (CTL) response restricted by HLA-B*57:01 and HLA-B*57:03 in chronic infection on the Gag epitope KAFSP EVIPMF (KF11; Gag 162 to 172). We previously showed that the HLA-B*57:03-KF11 response is associated with a >1-log-lower viral setpoint in C clade virus infection and that this response selects escape mutants within the epitope. We first examined the relationship of KF11 responses in B clade virus-infected subjects with HLA-B*57:01 to immune control and observed that a detectable KF11 response was associated with a >1-log-higher viral load (P=0.02). No evidence of HLA-B*57:01-KF11-associated selection pressure was identified in previous comprehensive analyses of >1,800 B clade virus-infected subjects. We then studied a B clade virus-infected cohort in Barbados, where HLA-B*57:03 is highly prevalent. In contrast to findings for B clade virusinfected subjects expressing HLA-B*57:01, we observed strong selection pressure driven by the HLA-B*57:03-KF11 response for the escape mutation S173T. This mutation reduces recognition of virus-infected cells by HLA-B*57:03-KF11 CTLs and is associated with a >1-log increase in viral load in HLA-B*57:03-positive subjects (P=0.009). We demonstrate functional constraints imposed by HIV clade relating to the residue at Gag 173 that explain the differential clade-specific escape patterns in HLAB*57:03 subjects. Further studies are needed to evaluate the role of the KF11 response in HLA-B*57:01-associated HIV disease protection. © 2014, American Society for Microbiology.
Authors & Co-Authors
Payne, Rebecca P.
United Kingdom, Oxford
University of Oxford
Branch, Songee L.
Barbados, Bridgetown
Queen Elizabeth Hospital Bridgetown
Kløverpris, Henrik N.
United Kingdom, Oxford
University of Oxford
South Africa, Durban
University of Kwazulu-natal
Matthews, Philippa C.
United Kingdom, Oxford
University of Oxford
Koofhethile, Catherine Kegakilwe
United Kingdom, Oxford
University of Oxford
Strong, T.
United Kingdom, Oxford
University of Oxford
Adland, Emily
United Kingdom, Oxford
University of Oxford
Leitman, Ellen M.
United Kingdom, Oxford
University of Oxford
Frater, John
United Kingdom, Oxford
Nuffield Department of Medicine
United Kingdom, Oxford
Nihr Oxford Biomedical Research Centre
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
Hunter, Eric
United States, Atlanta
Emory University
United States, Atlanta
Rollins School of Public Health
Haubrich, Richard H.
United States, La Jolla
University of California, San Diego
Mothe, Beatriz
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Edwards, Anne R.
United Kingdom, Oxford
Churchill Hospital
Riddell, Lynn A.
United Kingdom, Northampton
Northampton General Hospital
Chen, Fabian
United Kingdom, Reading
Royal Berkshire Hospital
Harrigan, P. Richard
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Brumme, Zabrina L.
Canada, Vancouver
British Columbia Centre for Excellence in Hiv-aids
Canada, Burnaby
Simon Fraser University
Mallal, Simon Alexander
Australia, Perth
Murdoch University
Australia, Perth
Royal Perth Hospital
John, Mina
Australia, Perth
Murdoch University
Australia, Perth
Royal Perth Hospital
Jooste, J. P.
South Africa
Kimberley Hospital
Shapiro, Roger L.
United States, Boston
Harvard T.h. Chan School of Public Health
Deeks, Steven G.
United States, San Francisco
Ucsf School of Medicine
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United States, Cambridge
Massachusetts Institute of Technology
Brander, Christian
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Spain, Barcelona
Institució Catalana de Recerca I Estudis Avançats
Landis, Robert Clive
Barbados, Bridgetown
Queen Elizabeth Hospital Bridgetown
Carlson, Jonathan M.
United States, Redmond
Microsoft Research
Prado, Julia Garcia
Spain, Badalona
Hospital Universitari Germans Trias I Pujol
Gouldera, Philip J.R.
South Africa, Durban
University of Kwazulu-natal
Statistics
Citations: 29
Authors: 29
Affiliations: 22
Identifiers
Doi:
10.1128/JVI.03303-13
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Cancer
Infectious Diseases
Study Design
Cohort Study