HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C.

Published

Journal Article

A variant 35 kb upstream of the HLA-C gene (-35C/T) was previously shown to associate with HLA-C mRNA expression level and steady-state plasma HIV RNA levels. We genotyped this variant in 1,698 patients of European ancestry with HIV. Individuals with known seroconversion dates were used for disease progression analysis and those with longitudinal viral load data were used for viral load analysis. We further tested cell surface expression of HLA-C in normal donors using an HLA-C-specific antibody. We show that the -35C allele is a proxy for high HLA-C cell surface expression, and that individuals with high-expressing HLA-C alleles progress more slowly to AIDS and control viremia significantly better than individuals with low HLA-C expressing alleles. These data strongly implicate high HLA-C expression levels in more effective control of HIV-1, potentially through better antigen presentation to cytotoxic T lymphocytes or recognition and killing of infected cells by natural killer cells.

Full Text

Cited Authors

  • Thomas, R; Apps, R; Qi, Y; Gao, X; Male, V; O'hUigin, C; O'Connor, G; Ge, D; Fellay, J; Martin, JN; Margolick, J; Goedert, JJ; Buchbinder, S; Kirk, GD; Martin, MP; Telenti, A; Deeks, SG; Walker, BD; Goldstein, D; McVicar, DW; Moffett, A; Carrington, M

Published Date

  • December 2009

Published In

Volume / Issue

  • 41 / 12

Start / End Page

  • 1290 - 1294

PubMed ID

  • 19935663

Pubmed Central ID

  • 19935663

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng.486

Language

  • eng