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

Brumme, ZL and John, M and Carlson, JM and Brumme, CJ and Chan, D and Brockman, MA and Swenson, LC and Tao, I and Szeto, S and Rosato, P and Sela, J and Kadie, CM and Frahm, N and Brander, C and Haas, DW and Riddler, SA and Haubrich, R and Walker, BD and Harrigan, PR and Heckerman, D and Mallal, S (2009) HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins. PLoS ONE, 4 (8).

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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. © 2009 Brumme et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Brumme, ZL John, M Carlson, JM Brumme, CJ Chan, D Brockman, MA Swenson, LC Tao, I Szeto, S Rosato, P Sela, J Kadie, CM Frahm, N Brander, C Haas, DW Riddler, SA riddler@pitt.edu RIDDLER Haubrich, R Walker, BD Harrigan, PR Heckerman, D Mallal, S
Contributors:	Contribution Contributors Name Email Pitt Username ORCID Editor Nixon, Douglas F. UNSPECIFIED UNSPECIFIED UNSPECIFIED
Date:	18 August 2009
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	4
Number:	8
DOI or Unique Handle:	10.1371/journal.pone.0006687
Refereed:	Yes
MeSH Headings:	Amino Acid Sequence; Cohort Studies; Gene Products, gag--chemistry; Gene Products, gag--immunology; Gene Products, nef--immunology; Gene Products, pol--immunology; Genotype; HIV Infections--immunology; HIV-1--genetics; HIV-1--immunology; HLA Antigens--immunology; Humans; Immune Evasion; Molecular Sequence Data
Other ID:	NLM PMC2723923
PubMed Central ID:	PMC2723923
PubMed ID:	19690614
Date Deposited:	03 Aug 2012 16:08
Last Modified:	05 Feb 2019 03:55
URI:	http://d-scholarship.pitt.edu/id/eprint/13264

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