@article{77a85de6ae2f4a7e8104e893cbaf92f9,
title = "HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C",
abstract = "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.",
author = "Rasmi Thomas and Richard Apps and Ying Qi and Xiaojiang Gao and Victoria Male and Colm O'Huigin and Geraldine O'Connor and Dongliang Ge and Jacques Fellay and Martin, {Jeffrey N.} and Joseph Margolick and Goedert, {James J.} and Susan Buchbinder and Kirk, {Gregory D.} and Martin, {Maureen P.} and Amalio Telenti and Deeks, {Steven G.} and Walker, {Bruce D.} and David Goldstein and McVicar, {Daniel W.} and Ashley Moffett and Mary Carrington",
note = "Funding Information: This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contracts HHSN261200800001E, N02-CP-55504, R01-DA04334 and R01-DA12568. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research was partially funded by a grant from the Bill & Melinda Gates Foundation as part of the Collaboration for AIDS Vaccine Discovery. We would also like to acknowledge the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation, and the SCOPE study was funded by the UL1 RR024131 (Clinical and Translational Sciences Award) and P30 AI27763 (Center for AIDS Research) grants. R.A. is funded by the Cambridge Center for Trophoblast Research. We also thank R. Fernando and the Anthony Nolan Research Institute for the Luminex analysis.",
year = "2009",
month = dec,
doi = "10.1038/ng.486",
language = "English (US)",
volume = "41",
pages = "1290--1294",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "12",
}