Influence of HLA-C Expression Level on HIV Control

Richard Apps(Ragon Institute of MGH, MIT and Harvard), Qi Ying(Ragon Institute of MGH, MIT and Harvard), Jonathan M. Carlson(Microsoft (United States)), Haoyan Chen(University of California, San Francisco), Xiaojiang Gao(Ragon Institute of MGH, MIT and Harvard), Rasmi Thomas(Science Applications International Corporation (United States)), Yuko Yuki(Ragon Institute of MGH, MIT and Harvard), Greg Q. Del Prete(Frederick National Laboratory for Cancer Research), Philip Goulder(Ragon Institute of MGH, MIT and Harvard), Zabrina L. Brumme(Simon Fraser University), Chanson J. Brumme(AIDS Vancouver), Mina John(Murdoch University), S. Mallal(Murdoch University), George W. Nelson(Frederick National Laboratory for Cancer Research), Ronald J. Bosch(Cancer Research And Biostatistics), David Heckerman(Microsoft (United States)), Judy L. Stein(Duke University), Kelly A. Soderberg(Duke University), M. Anthony Moody(Duke University), Thomas N. Denny(Duke University), Xue Zeng(University of California, San Francisco), Jing‐Yuan Fang(Shanghai Jiao Tong University), Ashley Moffett(University of Cambridge), Jeffrey D. Lifson(Frederick National Laboratory for Cancer Research), James J. Goedert(National Cancer Institute), Susan Buchbinder(San Francisco Department of Public Health), Gregory D. Kirk(Johns Hopkins University), Jacques Fellay(École Polytechnique Fédérale de Lausanne), Paul J. McLaren(École Polytechnique Fédérale de Lausanne), Steven G. Deeks(University of California, San Francisco), Florencia Pereyra(Ragon Institute of MGH, MIT and Harvard), Bruce D. Walker(Ragon Institute of MGH, MIT and Harvard), Nelson L. Michael(Walter Reed Army Institute of Research), Amy Weintrob(Uniformed Services University of the Health Sciences), Steven M. Wolinsky(Northwestern University), Wilson Liao(University of California, San Francisco), Mary Carrington(Ragon Institute of MGH, MIT and Harvard)
Science
April 4, 2013
10.1126/science.1232685
Cited by 382Open Access
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Abstract

A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA allelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.

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