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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
HIV-1 Adaptation to Antigen Processing Results in Population-Level Immune Evasion and Affects Subtype Diversification
Cell Reports, Volume 7, No. 2, Year 2014
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Description
The recent HIV-1 vaccine failures highlight the need to better understand virus-host interactions. One key question is why CD8+ Tcell responses to two HIV-Gag regions are uniquely associated with delayed disease progression only in patients expressing a few rare HLA class I variants when these regions encode epitopes presented by ~30 more common HLA variants. By combining epitope processing and computational analyses of the two HIV subtypes responsible for ~60% of worldwide infections, we identified a hitherto unrecognized adaptation to the antigen-processing machinery through substitutions at subtype-specific motifs. Multiple HLA variants presenting epitopes situated next to a given subtype-specific motif drive selection at this subtype-specific position, and epitope abundances correlate inversely with the HLA frequency distribution in affected populations. This adaptation reflects the sum of intrapatient adaptations, is predictable, facilitates viral subtype diversification, and increases global HIV diversity. Because low epitope abundance is associated with infrequent and weak Tcell responses, this most likely results inboth population-level immune evasion and inadequate responses in most people vaccinated with natural HIV-1 sequence constructs. Our results suggest that artificial sequence modifications at subtype-specific positions invitro could refocus and reverse the poor immunogenicity of HIV proteins. © 2014 The Authors.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4005910/bin/mmc1.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC4005910/bin/mmc2.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC4005910/bin/mmc3.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC4005910/bin/mmc4.pdf
Authors & Co-Authors
Tenzer, Stefan
Germany, Mainz
Universitätsmedizin Mainz
Crawford, Hayley
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Pymm, Phillip
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Gifford, Robert J.M.
United States, New York
Aaron Diamond Aids Research Center
Sreenu, Vattipally B.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Weimershaus, Mirjana
France, Paris
Cnrs Centre National de la Recherche Scientifique
deOliveira, Tulio
South Africa, Durban
University of Kwazulu-natal
United Kingdom, London
University College London
Burgevin, Anne
France, Paris
Cnrs Centre National de la Recherche Scientifique
Gerstoft, Jan
Denmark, Copenhagen
Rigshospitalet
Akkad, Nadja
Germany, Mainz
Universitätsmedizin Mainz
Lunn, Daniel
United Kingdom, Oxford
University of Oxford
Fugger, Lars
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Bell, John I.
United Kingdom, Oxford
University of Oxford
Schild, Hansjörg I.
Germany, Mainz
Universitätsmedizin Mainz
vanEndert, Peter
France, Paris
Cnrs Centre National de la Recherche Scientifique
Iversen, Astrid K.N.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Statistics
Citations: 16
Authors: 16
Affiliations: 9
Identifiers
Doi:
10.1016/j.celrep.2014.03.031
e-ISSN:
22111247
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study