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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
HLA-associated clinical progression correlates with epitope reversion rates in early human immunodeficiency virus infection
Journal of Virology, Volume 83, No. 3, Year 2009
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Description
Human immunodeficiency virus type 1 (HIV-1) can evade immunity shortly after transmission to a new host but the clinical significance of this early viral adaptation in HIV infection is not clear. We present an analysis of sequence variation from a longitudinal cohort study of HIV adaptation in 189 acute seroconverters followed for up to 3 years. We measured the rates of variation within well-defined epitopes to determine associations with the HLA-linked hazard of disease progression. We found early reversion across both the gag and pol genes, with a 10-fold faster rate of escape in gag (2.2 versus 0.27 forward mutations/1,000 amino acid sites). For most epitopes (23/34), variation in the HLA-matched and HLA-unmatched controls was similar. For a minority of epitopes (8/34, and generally associated with HLA class I alleles that confer clinical benefit), new variants appeared early and consistently over the first 3 years of infection. Reversion occurred early at a rate which was HLA-dependent and correlated with the HLA class 1-associated relative hazard of disease progression and death (P = 0.0008), reinforcing the association between strong cytotoxic T-lymphocyte responses, viral fitness, and disease status. These data provide a comprehensive overview of viral adaptation in the first 3 years of infection. Our findings of HLA-dependent reversion suggest that costs are borne by some escape variants which may benefit the host, a finding contrary to a simple immune evasion paradigm. These epitopes, which are both strongly and frequently recognized, and for which escape involves a high cost to the virus, have the potential to optimize vaccine design. Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Duda, Anna
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Nuffield Department of Medicine
Fox, Julie Meriel
United Kingdom, London
Imperial College London
Robinson, Nicola
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Nuffield Department of Medicine
Kaye, Steve
United Kingdom, London
Imperial College London
Fryer, Helen R.
United Kingdom, Oxford
Nuffield Department of Medicine
United Kingdom, Oxford
University of Oxford
Carrington, Mary N.
United States, Frederick
National Cancer Institute at Frederick
McClure, Myra Olga
United Kingdom, London
Imperial College London
McLean, Angela R.
United Kingdom, Oxford
Nuffield Department of Medicine
United Kingdom, Oxford
University of Oxford
Fidler, Sarah J.
United Kingdom, London
Imperial College London
Weber, Jonathan N.
United Kingdom, London
Imperial College London
Phillips, Rodney E.
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Nuffield Department of Medicine
Frater, John
United Kingdom, Oxford
University of Oxford
United Kingdom, Oxford
Nuffield Department of Medicine
Breckenridge, Alasdair M.
Unknown Affiliation
Conlon, Christopher P.
Unknown Affiliation
Cooper, David A.
Unknown Affiliation
Conradie, Francesca M.
Unknown Affiliation
Kaldor, John M.
Unknown Affiliation
Schechter, Mauro T.
Unknown Affiliation
Kaleebu, Pontiano P.
Unknown Affiliation
Ramjee, Gita A.
Unknown Affiliation
Ssali, Francis N.
Unknown Affiliation
Tambussi, Giuseppe
Unknown Affiliation
Statistics
Citations: 39
Authors: 22
Affiliations: 4
Identifiers
Doi:
10.1128/JVI.01545-08
ISSN:
0022538X
Research Areas
Environmental
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative