Influence of HLA-C expression level on HIV control

Apps, R., Qi, Y., Carlson, J.M., Chen, H., Gao, X., Thomas, R., Yuki, Y., Del Prete, G.Q., Goulder, P., Brumme, Z.L., Brumme, C.J., John, M., Mallal, S., Nelson, G., Bosch, R., Heckerman, D., Stein, J.L., Soderberg, K.A., Moody, M.A., Denny, T.N., Zeng, X., Fang, J., Moffett, A., Lifson, J.D., Goedert, J.J., Buchbinder, S., Kirk, G.D., Fellay, J., McLaren, P., Deeks, S.G., Pereyra, F., Walker, B., Michael, N.L., Weintrob, A., Wolinsky, S., Liao, W. and Carrington, M. (2013) Influence of HLA-C expression level on HIV control. Science, 340 (6128). pp. 87-91.

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.

Item Type:	Journal Article
Murdoch Affiliation(s):	Institute for Immunology and Infectious Diseases
Publisher:	American Association for the Advancement of Science
URI:	http://researchrepository.murdoch.edu.au/id/eprint/14965

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