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

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 functi...

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Bibliographic Details
Published in:PloS one 2012-10, Vol.7 (10), p.e47799-e47799
Main Authors: Matthews, Philippa C, Listgarten, Jennifer, Carlson, Jonathan M, Payne, Rebecca, Huang, Kuan-Hsiang Gary, Frater, John, Goedhals, Dominique, Steyn, Dewald, van Vuuren, Cloete, Paioni, Paolo, Jooste, Pieter, Ogwu, Anthony, Shapiro, Roger, Mncube, Zenele, Ndung'u, Thumbi, Walker, Bruce D, Heckerman, David, Goulder, Philip J R
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Adult
Africa, Southern
AIDS
Alleles
Analysis of Variance
Antigenic determinants
Biology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - virology
Complementarity
Computer applications
Control
Disease control
Gene Frequency
Genotype
HIV
HIV infections
HIV Infections - genetics
HIV Infections - immunology
HIV Infections - virology
HIV-1 - immunology
HLA antigens
HLA Antigens - genetics
HLA Antigens - immunology
Hospitals
Human immunodeficiency virus
Humans
Immunity, Cellular - genetics
Immunology
Infections
Internal medicine
Linkage Disequilibrium
Lymphocytes
Lymphocytes T
Medical research
Medicine
Mutation
Pathogenesis
Patient outcomes
Predictive control
Proteomes
Research Design
Viremia - genetics
Viremia - immunology
Viremia - virology
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Summary: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. 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
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0047799