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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Broad and gag-biased HIV-1 epitope repertoires are associated with lower viral loads
PLoS ONE, Volume 3, No. 1, Article e1424, Year 2008
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Description
Background. HLA class-I alleles differ in their ability to control HIV replication through cell-mediated immune responses. No consistent associations have been found between the breadth of Cytotoxic T Lymphocytes (CTL) responses and the control of HIV-1, and it is unknown whether the size or distribution of the viral proteome-wide epitope repertoire, i.e., the intrinsic ability to present fewer, more or specific viral epitopes, could affect clinical markers of disease progression. Methodology Principal Findings. We used an epitope prediction model to identify all epitope motifs in a set of 302 HIV-1 full-length proteomes according to each individual's HLA (Human Leukocyte Antigen) genotype. The epitope repertoire, i.e., the number of predicted epitopes per HIV-1 proteome, varied considerably between HLA alleles and thus among individual proteomes. In a subgroup of 270 chronically infected individuals, we found that lower viral loads and higher CD4 counts were associated with a larger predicted epitope repertoire. Additionally, in Gag and Rev only, more epitopes were restricted by alleles associated with low viral loads than by alleles associated with higher viral loads. Conclusions/Significance. This comprehensive analysis puts forth the epitope repertoire as a mechanistic component of the multi-faceted HIV-specific CTL response. The favorable impact on markers of disease status of the propensity to present more HLA binding peptides and specific proteins gives impetus to vaccine design strategies that seek to elicit responses to a broad array of HIV-1 epitopes, and suggest a particular focus on Gag. © 2008 Rolland et al.
Authors & Co-Authors
Rolland, Morgane M.
United States, Seattle
University of Washington School of Medicine
Heckerman, David E.
United States, Redmond
Microsoft Research
Deng, Wenjie
United States, Seattle
University of Washington School of Medicine
Rousseau, Christine M.
United States, Seattle
University of Washington School of Medicine
Coovadia, Hoosen Mahomed
South Africa, Durban
University of Kwazulu-natal
Bishop, Karen S.
South Africa, Durban
University of Kwazulu-natal
Goulder, Philip Jeremy Renshaw
South Africa, Durban
University of Kwazulu-natal
United Kingdom, Oxford
Nuffield Department of Medicine
United States, Boston
Massachusetts General Hospital
Walker, Bruce D.
South Africa, Durban
University of Kwazulu-natal
United States, Boston
Massachusetts General Hospital
Brander, Christian
United States, Boston
Massachusetts General Hospital
Mullins, James I.
United States, Seattle
University of Washington School of Medicine
Statistics
Citations: 171
Authors: 10
Affiliations: 5
Identifiers
Doi:
10.1371/journal.pone.0001424
e-ISSN:
19326203
Research Areas
Genetics And Genomics
Infectious Diseases