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).
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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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 | | | |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Nixon, Douglas F. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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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