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Influence of HLA-C expression level on HIV control.

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Date
2013-04-05
Authors
Apps, Richard
Qi, Ying
Carlson, Jonathan M
Chen, Haoyan
Gao, Xiaojiang
Thomas, Rasmi
Yuki, Yuko
Del Prete, Greg Q
Goulder, Philip
Brumme, Zabrina L
Brumme, Chanson J
John, Mina
Mallal, Simon
Nelson, George
Bosch, Ronald
Heckerman, David
Stein, Judy L
Soderberg, Kelly A
Moody, M Anthony
Denny, Thomas N
Zeng, Xue
Fang, Jingyuan
Moffett, Ashley
Lifson, Jeffrey D
Goedert, James J
Buchbinder, Susan
Kirk, Gregory D
Fellay, Jacques
McLaren, Paul
Deeks, Steven G
Pereyra, Florencia
Walker, Bruce
Michael, Nelson L
Weintrob, Amy
Wolinsky, Steven
Liao, Wilson
Carrington, Mary
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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.
Type
Journal article
Subject
African Americans
Alleles
Amino Acid Sequence
Anti-Retroviral Agents
Crohn Disease
Gene Expression Regulation
HIV
HIV Infections
HLA-C Antigens
Humans
Immunodominant Epitopes
Molecular Sequence Data
Mutation
Peptide Fragments
Polymorphism, Single Nucleotide
T-Lymphocytes, Cytotoxic
Viral Load
Permalink
https://hdl.handle.net/10161/14728
Published Version (Please cite this version)
10.1126/science.1232685
Publication Info
Apps, Richard; Qi, Ying; Carlson, Jonathan M; Chen, Haoyan; Gao, Xiaojiang; Thomas, Rasmi; ... Carrington, Mary (2013). Influence of HLA-C expression level on HIV control. Science, 340(6128). pp. 87-91. 10.1126/science.1232685. Retrieved from https://hdl.handle.net/10161/14728.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Denny

Thomas Norton Denny

Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor of Medicine in the Department of Medicine at Duke University Medical Center. He is also an Affiliate Member of the Duke Global Health Institute. Previously, he served on the Health Sector Advisory Council of the Duke University Fuquay School of Business. Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Moody

Michael Anthony Moody

Professor of Pediatrics
Tony Moody, MD is a Professor in the Department of Pediatrics, Division of Infectious Diseases and Professor in the Department of Integrative Immunobiology at Duke University Medical Center. Research in the Moody lab is focused on understanding the B cell responses during infection, vaccination, and disease. The lab has become a resource for human phenotyping, flow characterization, staining and analysis at the Duke Human Vaccine Institute (DHVI). The Moody lab is currently funded to study in
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