Co-operative additive effects between HLA alleles in control of HIV-1.

Autor: Philippa C Matthews, Jennifer Listgarten, Jonathan M Carlson, Rebecca Payne, Kuan-Hsiang Gary Huang, John Frater, Dominique Goedhals, Dewald Steyn, Cloete van Vuuren, Paolo Paioni, Pieter Jooste, Anthony Ogwu, Roger Shapiro, Zenele Mncube, Thumbi Ndung'u, Bruce D Walker, David Heckerman, Philip J R Goulder
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: PLoS ONE, Vol 7, Iss 10, p e47799 (2012)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0047799
Popis: BACKGROUND:HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles--irrespective of linkage disequilibrium--function co-operatively. METHODOLOGY/PRINCIPAL FINDINGS:We here refined a computational approach to the analysis of >2000 subjects infected with C-clade HIV first to discern the individual effect of each allele on disease control, and second to identify pairs of alleles that mediate 'co-operative additive' effects, either to improve disease suppression or to contribute to immunological failure. We identified six pairs of HLA class I alleles that have a co-operative additive effect in mediating HIV disease control and four hazardous pairs of alleles that, occurring together, are predictive of worse disease outcomes (q
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