Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells

Author:

Ramsuran Veron1234ORCID,Naranbhai Vivek1245ORCID,Horowitz Amir6ORCID,Qi Ying1,Martin Maureen P.1,Yuki Yuko1,Gao Xiaojiang1,Walker-Sperling Victoria7ORCID,Del Prete Gregory Q.8ORCID,Schneider Douglas K.8,Lifson Jeffrey D.8,Fellay Jacques9ORCID,Deeks Steven G.10ORCID,Martin Jeffrey N.11ORCID,Goedert James J.12,Wolinsky Steven M.13,Michael Nelson L.14ORCID,Kirk Gregory D.15,Buchbinder Susan101116,Haas David17ORCID,Ndung’u Thumbi2181920ORCID,Goulder Philip1821ORCID,Parham Peter22,Walker Bruce D.21823ORCID,Carlson Jonathan M.24ORCID,Carrington Mary12ORCID

Affiliation:

1. Cancer and Inflammation Program, Leidos Biomedical Research, 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, Cambridge, MA 02139, USA.

3. KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

4. Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa.

5. Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

6. Department of Oncological Sciences, Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

7. Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.

8. AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.

9. School of Life Sciences, École Polytechnique Fédérale de Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland.

10. Department of Medicine University of California, San Francisco, CA 94143, USA.

11. Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94143, USA.

12. Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.

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

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

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

16. San Francisco Department of Public Health, HIV Research Section, San Francisco, CA 94102, USA.

17. Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

18. African Health Research Institute, Durban, South Africa.

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

20. Max Planck Institute for Infection Biology, Berlin, Germany.

21. Department of Paediatrics, University of Oxford, Oxford, UK.

22. Departments of Structural Biology and Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.

23. Institute for Medical and Engineering Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

24. Microsoft Research, Redmond, WA 98052, USA.

Abstract

Inhibiting natural killer cells in AIDS The human leukocyte antigen (HLA) gene complex varies enormously among individuals and helps explain individual variation in immunity to infectious diseases. Ramsuran et al. examined data from almost 10,000 HIV infections. Expression of the HLA-A and - B alleles was associated with higher viral load, reduced CD4 + T cell counts, and accelerated progression to AIDS. Higher levels of HLA-A expression increased expression of HLA-E , which blocks a specific receptor (NKG2A) on the immune cells that normally eliminate virus-infected cells. Thus, targeting NKG2A might provide a therapeutic avenue for HIV treatment. Science , this issue p. 86

Funder

Wellcome Trust

Rhodes Scholarships

Swiss National Science Foundation

NIH

NIAID

Collaboration for AIDS Vaccine Discovery of the Bill and Melinda Gates Foundation

NIH CFAR

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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