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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Evolution of HLA-B 5703 hiv-1 escape mutations in HLA-B 5703-positive individuals and their transmission recipients
Journal of Experimental Medicine, Volume 206, No. 4, Year 2009
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Description
HLA-B 57 is the class I allele most consistently associated with control of human immunodeficiency virus (HIV) replication, which may be linked to the specific HIV peptides that this allele presents to cytotoxic T lymphocytes (CTLs), and the resulting efficacy of these cellular immune responses. In two HIV C clade-infected populations in South Africa and Zambia, we sought to elucidate the role of HLA-B5703 in HIV disease outcome. HLA-B5703- restricted CTL responses select for escape mutations in three Gag p24 epitopes, in a predictable order. We show that the accumulation of these mutations sequentially reduces viral replicative capacity in vitro. Despite this, in vivo data demonstrate that there is ultimately an increase in viral load concomitant with evasion of all three HLA-B5703-restricted CTL responses. In HLA-B5703-mismatched recipients, the previously described early benefit of transmitted HLA-B5703-associated escape mutations is abrogated by the increase in viral load coincident with reversion. Rapid disease progression is observed in HLA-matched recipients to whom mutated virus is transmitted. These data demonstrate that, although costly escape from CTL responses can progressively attenuate the virus, high viral loads develop in the absence of adequate, continued CTL responses. These data underline the need for a CTL vaccine against multiple conserved epitopes. © 2009 Crawford et al.
Authors & Co-Authors
Crawford, Hayley
United Kingdom, Oxford
University of Oxford
Lumm, Wendy
United States, Atlanta
Emory University
Leslie, Alasdair J.
United Kingdom, Oxford
University of Oxford
Schaefer, Malinda R.
United States, Atlanta
Emory University
Boeras, Debrah I.
United States, Atlanta
Emory University
Prado, Julia Garcia
United Kingdom, Oxford
University of Oxford
Tang, Jianming
United States, Birmingham
The University of Alabama at Birmingham
Farmer, Paul K.
United States, Atlanta
Emory University
Ndung'u, Thumbi P.
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
Lakhi, Shabir
Zambia, Lusaka
Zambia-emory Hiv Research Project
Gilmour, Jill W.
United Kingdom, London
Chelsea and Westminster Hospital
Goepfert, Paul A.
Unknown Affiliation
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
Kaslow, Richard A.
United States, Birmingham
The University of Alabama at Birmingham
Mulenga, Joseph
Zambia, Lusaka
Zambia-emory Hiv Research Project
Allen, Susan A.
United States, Atlanta
Emory University
Zambia, Lusaka
Zambia-emory Hiv Research Project
Goulder, Philip Jeremy Renshaw
United Kingdom, Oxford
University of Oxford
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
Hunter, Eric
United States, Atlanta
Emory University
Zambia, Lusaka
Zambia-emory Hiv Research Project
Zambia, Lusaka
Zambia Blood Transfusion Service
Statistics
Citations: 196
Authors: 18
Affiliations: 9
Identifiers
Doi:
10.1084/jem.20081984
ISSN:
00221007
e-ISSN:
15409538
Research Areas
Genetics And Genomics
Infectious Diseases
Study Locations
South Africa
Zambia