Details

Autor(en) / Beteiligte

• 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
• Nixon, Douglas F.

Titel

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

Ist Teil von

• PloS one, 2009-08, Vol.4 (8), p.e6687-e6687

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2009

Link zum Volltext

Quelle

EZB Free E-Journals

Beschreibungen/Notizen

• 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. 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< or =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 approximately 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< or =0.05, illustrating the dense and complex networks of linked escape and secondary/compensatory mutations. 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.