The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.
Publication/Presentation Date
12-10-2010
Abstract
Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.
Volume
330
Issue
6010
First Page
1551
Last Page
1557
ISSN
1095-9203
Published In/Presented At
International HIV Controllers Study, Pereyra, F., Jia, X., McLaren, P. J., Telenti, A., de Bakker, P. I., Walker, B. D., Ripke, S., Brumme, C. J., Pulit, S. L., Carrington, M., Kadie, C. M., Carlson, J. M., Heckerman, D., Graham, R. R., Plenge, R. M., Deeks, S. G., Gianniny, L., Crawford, G., Sullivan, J., … Zhao, M. (2010). The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science (New York, N.Y.), 330(6010), 1551–1557. https://doi.org/10.1126/science.1195271
Disciplines
Medicine and Health Sciences
PubMedID
21051598
Department(s)
Department of Medicine
Document Type
Article