dc.contributor.author | Brumme, Zabrina L. | |
dc.contributor.author | John, Mina | |
dc.contributor.author | Carlson, Jonathan M. | |
dc.contributor.author | Brumme, Chanson J. | |
dc.contributor.author | Chan, Dennison | |
dc.contributor.author | Brockman, Mark A. | |
dc.contributor.author | Swenson, Luke C. | |
dc.contributor.author | Tao, Iris | |
dc.contributor.author | Szeto, Sharon | |
dc.contributor.author | Rosato, Pamela | |
dc.contributor.author | Sela, Jennifer | |
dc.contributor.author | Kadie, Carl M. | |
dc.contributor.author | Frahm, Nicole | |
dc.contributor.author | Brander, Christian | |
dc.contributor.author | Haas, David W. | |
dc.contributor.author | Riddler, Sharon A. | |
dc.contributor.author | Haubrich, Richard | |
dc.contributor.author | Walker, Bruce D. | |
dc.contributor.author | Harrigan, P. Richard | |
dc.contributor.author | Heckerman, David | |
dc.contributor.author | Mallal, Simon | |
dc.date.accessioned | 2010-03-10T17:53:54Z | |
dc.date.available | 2010-03-10T17:53:54Z | |
dc.date.issued | 2009-08 | |
dc.date.submitted | 2009-05 | |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/52468 | |
dc.description.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. | en |
dc.description.sponsorship | National Institute of Allergy and Infectious Diseases (Award Number U01AI068636 and AI068634) | en |
dc.language.iso | en_US | |
dc.publisher | Public Library of Science | en |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.pone.0006687 | en |
dc.rights | Creative Commons Attribution | en |
dc.rights.uri | http://creativecommons.org/licenses/by/2.5/ | en |
dc.source | PLoS | en |
dc.subject | Bill and Melinda Gates Foundation | en |
dc.title | HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins | en |
dc.type | Article | en |
dc.identifier.citation | Brumme, Zabrina L. et al. “HLA-Associated Immune Escape Pathways in HIV-1 Subtype B Gag, Pol and Nef Proteins.” PLoS ONE 4.8 (2009): e6687. | en |
dc.contributor.department | Ragon Institute of MGH, MIT and Harvard | en_US |
dc.contributor.approver | Brander, Christian | |
dc.contributor.mitauthor | Walker, Bruce D. | |
dc.contributor.mitauthor | Frahm, Nicole | |
dc.contributor.mitauthor | Sela, Jennifer | |
dc.contributor.mitauthor | Rosato, Pamela | |
dc.contributor.mitauthor | Brockman, Mark A. | |
dc.contributor.mitauthor | Brumme, Chanson J. | |
dc.contributor.mitauthor | Brumme, Zabrina L. | |
dc.contributor.mitauthor | Brander, Christian | |
dc.relation.journal | PLoS ONE | en |
dc.eprint.version | Final published version | en |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en |
dspace.orderedauthors | Brumme, Zabrina L.; John, Mina; Carlson, Jonathan M.; Brumme, Chanson J.; Chan, Dennison; Brockman, Mark A.; Swenson, Luke C.; Tao, Iris; Szeto, Sharon; Rosato, Pamela; Sela, Jennifer; Kadie, Carl M.; Frahm, Nicole; Brander, Christian; Haas, David W.; Riddler, Sharon A.; Haubrich, Richard; Walker, Bruce D.; Harrigan, P. Richard; Heckerman, David; Mallal, Simon | en |
mit.license | PUBLISHER_CC | en |
mit.metadata.status | Complete | |