HLA-Associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins

Z.L. Brumme; M. John; J.M. Carlson; C.J. Brumme; D. Chan; M.A. Brockman; L.C. Swenson; I. Tao; S. Szeto; P. Rosato; J. Sela; C.M. Kadie; N. Frahm; C. Brander; D.W. Haas; S.A. Riddler; R. Haubrich; B.D. Walker; P.R. Harrigan; D. Heckerman; S. Mallal; D.F. Nixon

doi:10.1371/journal.pone.0006687

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HLA-Associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins

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HLA-Associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins

Z.L. Brumme, M. John, J.M. Carlson, C.J. Brumme, D. Chan, M.A. Brockman, L.C. Swenson, I. Tao, S. Szeto, P. Rosato, …

PLoS ONE, Vol.4(8), e6687

2009

DOI: https://doi.org/10.1371/journal.pone.0006687

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Abstract

Background: Despite the extensive genetic diversity of HIV-1, viral evolution in response to immune selective pressures follows broadly predictable mutational patterns. Sites and pathways of Human Leukocyte-Antigen (HLA)-associated polymorphisms in HIV-1 have been identified through the analysis of population-level data, but the full extent of immune escape pathways remains incompletely characterized. Here, in the largest analysis of HIV-1 subtype B sequences undertaken to date, we identify HLA-associated polymorphisms in the three HIV-1 proteins most commonly considered in cellular-based vaccine strategies. Results are organized into protein-wide escape maps illustrating the sites and pathways of HLA-driven viral evolution. Methodology/Principal Findings: HLA-associated polymorphisms were identified in HIV-1 Gag, Pol and Nef in a multicenter cohort of >1500 chronically subtype-B infected, treatment-naïve individuals from established cohorts in Canada, the USA and Western Australia. At q≤0.05, 282 codons commonly mutating under HLA-associated immune pressures were identified in these three proteins. The greatest density of associations was observed in Nef (where close to 40% of codons exhibited a significant HLA association), followed by Gag then Pol (where ∼15-20% of codons exhibited HLA associations), confirming the extensive impact of immune selection on HIV evolution and diversity. Analysis of HIV codon covariation patterns identified over 2000 codon-codon interactions at q≤0.05, illustrating the dense and complex networks of linked escape and secondary/compensatory mutations. Conclusions/Significance: The immune escape maps and associated data are intended to serve as a user-friendly guide to the locations of common escape mutations and covarying codons in HIV-1 subtype B, and as a resource facilitating the systematic identification and classification of immune escape mutations. These resources should facilitate research in HIV epitope discovery and host-pathogen co-evolution, and are relevant to the continued search for an effective CTL-based AIDS vaccine.

Details

Title: HLA-Associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins
Authors/Creators: Z.L. Brumme (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
M. John (Author/Creator) - Royal Perth Hospital
J.M. Carlson (Author/Creator) - Microsoft (United States)
C.J. Brumme (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
D. Chan (Author/Creator) - AIDS Vancouver
M.A. Brockman (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
L.C. Swenson (Author/Creator) - AIDS Vancouver
I. Tao (Author/Creator) - AIDS Vancouver
S. Szeto (Author/Creator) - AIDS Vancouver
P. Rosato (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
J. Sela (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
C.M. Kadie (Author/Creator) - Microsoft (United States)
N. Frahm (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
C. Brander (Author/Creator) - Institució Catalana de Recerca i Estudis Avançats
D.W. Haas (Author/Creator) - Vanderbilt University
S.A. Riddler (Author/Creator) - University of Pittsburgh
R. Haubrich (Author/Creator) - University of California San Diego
B.D. Walker (Author/Creator) - Howard Hughes Medical Institute
P.R. Harrigan (Author/Creator) - University of British Columbia
D. Heckerman (Author/Creator) - Microsoft (Canada)
S. Mallal (Author/Creator) - Royal Perth Hospital
D.F. Nixon (Author/Creator)
Publication Details: PLoS ONE, Vol.4(8), e6687
Publisher: Public Library of Science
Identifiers: 991005541470707891
Copyright: © 2009 Brumme et al.
Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV Pathogenesis
Web Of Science research areas: Virology
ESI research areas: Microbiology