Influence of HLA-C Expression Level on HIV Control

Author:

Apps Richard12,Qi Ying12,Carlson Jonathan M.3,Chen Haoyan45,Gao Xiaojiang12,Thomas Rasmi1,Yuki Yuko12,Del Prete Greg Q.6,Goulder Philip278,Brumme Zabrina L.910,Brumme Chanson J.9,John Mina11,Mallal Simon11,Nelson George12,Bosch Ronald13,Heckerman David3,Stein Judy L.14,Soderberg Kelly A.14,Moody M. Anthony14,Denny Thomas N.14,Zeng Xue415,Fang Jingyuan5,Moffett Ashley16,Lifson Jeffrey D.6,Goedert James J.17,Buchbinder Susan18,Kirk Gregory D.19,Fellay Jacques20,McLaren Paul20,Deeks Steven G.21,Pereyra Florencia2,Walker Bruce2,Michael Nelson L.22,Weintrob Amy23,Wolinsky Steven24,Liao Wilson4,Carrington Mary12

Affiliation:

1. Cancer and Inflammation Program, Laboratory of Experimental Immunology, Science Applications International Corporation (SAIC)-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

2. Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Boston, MA 02114, USA.

3. Microsoft Research, eScience Group, Los Angeles, CA 90024, USA.

4. Department of Dermatology, University of California, San Francisco, CA 94115, USA.

5. Department of Gastroenterology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Diseases, Shanghai 200001, China.

6. AIDS and Cancer Virus Program, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

7. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa.

8. Department of Paediatrics, Oxford University, Oxford OX1 3SY, UK.

9. British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada V6Z 1Y6.

10. Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada V5A 1S6.

11. Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, 6150.

12. Basic Research Program, Center for Cancer Research Genetics Core, SAIC-Frederick, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

13. Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA 02115, USA.

14. Duke Human Vaccine Institute, Duke University, Durham, NC 27710, USA.

15. Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.

16. Department of Pathology, University of Cambridge, CB2 1QP, UK.

17. Infectious and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20892, USA.

18. San Francisco Department of Public Health, Bridge HIV, San Francisco, CA 94102, USA.

19. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.

20. Institute of Microbiology, University Hospital Lausanne and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.

21. Department of Medicine, University of California, San Francisco, CA 94105, USA.

22. U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.

23. Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD, 20817, USA.

24. Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.

Abstract

Thwarting HIV Multiple genome-wide association studies have revealed that human leukocyte antigen (HLA) genes of the major histocompatibility complex locus have the strongest impact on HIV. In particular, a single-nucleotide polymorphism 35 base pairs upstream of HLA-C shows significant association with viral load and protection against HIV. How HLA-C mediates these effects is unknown. Apps et al. (p. 87 ) now demonstrate that increasing surface expression of HLA-C is associated with reduced viral load and reduced rate of progression to low CD4 + T cell counts in African and European Americans. High HLA-C expression likely promoted improved HIV control through a more effective cytotoxic CD8 + T cell response. In contrast to HIV infection, high HLA-C expression was associated with a higher risk of the inflammatory bowel disease, Crohn's disease.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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