PMID- 29302013
OWN - NLM
STAT- MEDLINE
DCOM- 20180410
LR  - 20210703
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 359
IP  - 6371
DP  - 2018 Jan 5
TI  - Elevated HLA-A expression impairs HIV control through inhibition of 
      NKG2A-expressing cells.
PG  - 86-90
LID - 10.1126/science.aam8825 [doi]
AB  - The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface 
      proteins that are critical for immunity. HLA-A expression levels vary in an 
      allele-dependent manner, diversifying allele-specific effects beyond 
      peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 
      cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated 
      HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that 
      specifically binds and determines expression levels of HLA-E, the ligand for the 
      inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor 
      NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious 
      effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition 
      impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of 
      HLA-E:NKG2A interaction may yield benefit in HIV disease.
CI  - Copyright (c) 2017, American Association for the Advancement of Science.
FAU - Ramsuran, Veron
AU  - Ramsuran V
AUID- ORCID: 0000-0003-1590-9893
AD  - Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139, USA.
AD  - KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of 
      Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, 
      South Africa.
AD  - Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, 
      South Africa.
FAU - Naranbhai, Vivek
AU  - Naranbhai V
AUID- ORCID: 0000-0003-4281-8882
AD  - Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139, USA.
AD  - Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, 
      South Africa.
AD  - Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, 
      University of Oxford, Oxford, UK.
FAU - Horowitz, Amir
AU  - Horowitz A
AUID- ORCID: 0000-0003-4602-1440
AD  - Department of Oncological Sciences, Precision Immunology Institute, Icahn School 
      of Medicine at Mount Sinai, New York, NY 10029, USA.
FAU - Qi, Ying
AU  - Qi Y
AD  - Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Martin, Maureen P
AU  - Martin MP
AD  - Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Yuki, Yuko
AU  - Yuki Y
AD  - Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Gao, Xiaojiang
AU  - Gao X
AD  - Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Walker-Sperling, Victoria
AU  - Walker-Sperling V
AUID- ORCID: 0000-0001-7847-7931
AD  - Cancer and Inflammation Program, Center for Cancer Research, National Cancer 
      Institute, National Institutes of Health, Frederick, MD 21702, USA.
FAU - Del Prete, Gregory Q
AU  - Del Prete GQ
AUID- ORCID: 0000-0001-6180-5361
AD  - AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Schneider, Douglas K
AU  - Schneider DK
AD  - AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Lifson, Jeffrey D
AU  - Lifson JD
AD  - AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA.
FAU - Fellay, Jacques
AU  - Fellay J
AUID- ORCID: 0000-0002-8240-939X
AD  - School of Life Sciences, Ecole Polytechnique Federale de Lausanne, and Swiss 
      Institute of Bioinformatics, Lausanne, Switzerland.
FAU - Deeks, Steven G
AU  - Deeks SG
AUID- ORCID: 0000-0001-6371-747X
AD  - Department of Medicine University of California, San Francisco, CA 94143, USA.
FAU - Martin, Jeffrey N
AU  - Martin JN
AUID- ORCID: 0000-0002-9773-3256
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA 94143, USA.
FAU - Goedert, James J
AU  - Goedert JJ
AD  - Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and 
      Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 
      20850, USA.
FAU - Wolinsky, Steven M
AU  - Wolinsky SM
AD  - Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern 
      University, Chicago, IL 60611, USA.
FAU - Michael, Nelson L
AU  - Michael NL
AUID- ORCID: 0000-0001-5882-5548
AD  - U.S. Military HIV Research Program, Walter Reed Army Institute of Research, 
      Silver Spring, MD 20910, USA.
FAU - Kirk, Gregory D
AU  - Kirk GD
AD  - Department of Epidemiology, Johns Hopkins University Bloomberg School of Public 
      Health, Baltimore, MD 21205, USA.
FAU - Buchbinder, Susan
AU  - Buchbinder S
AD  - Department of Medicine University of California, San Francisco, CA 94143, USA.
AD  - Department of Epidemiology and Biostatistics, University of California, San 
      Francisco, CA 94143, USA.
AD  - San Francisco Department of Public Health, HIV Research Section, San Francisco, 
      CA 94102, USA.
FAU - Haas, David
AU  - Haas D
AUID- ORCID: 0000-0002-5813-1594
AD  - Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
FAU - Ndung'u, Thumbi
AU  - Ndung'u T
AUID- ORCID: 0000-0003-2962-3992
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139, USA.
AD  - African Health Research Institute, Durban, South Africa.
AD  - HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. 
      Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
AD  - Max Planck Institute for Infection Biology, Berlin, Germany.
FAU - Goulder, Philip
AU  - Goulder P
AUID- ORCID: 0000-0002-9842-4674
AD  - African Health Research Institute, Durban, South Africa.
AD  - Department of Paediatrics, University of Oxford, Oxford, UK.
FAU - Parham, Peter
AU  - Parham P
AD  - Departments of Structural Biology and Microbiology and Immunology, Stanford 
      University, Stanford, CA 94305, USA.
FAU - Walker, Bruce D
AU  - Walker BD
AUID- ORCID: 0000-0001-6122-9245
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139, USA.
AD  - African Health Research Institute, Durban, South Africa.
AD  - Institute for Medical and Engineering Sciences, Massachusetts Institute of 
      Technology, Cambridge, MA 02139, USA.
FAU - Carlson, Jonathan M
AU  - Carlson JM
AUID- ORCID: 0000-0001-6618-3653
AD  - Microsoft Research, Redmond, WA 98052, USA.
FAU - Carrington, Mary
AU  - Carrington M
AUID- ORCID: 0000-0002-2692-2180
AD  - Cancer and Inflammation Program, Leidos Biomedical Research, Inc., Frederick 
      National Laboratory for Cancer Research, Frederick, MD 21702, USA. 
      carringm@mail.nih.gov.
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139, USA.
LA  - eng
GR  - R01 AI133673/AI/NIAID NIH HHS/United States
GR  - R01 AI077505/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - UM1 AI068634/AI/NIAID NIH HHS/United States
GR  - UM1 AI069496/AI/NIAID NIH HHS/United States
GR  - P30 AI027763/AI/NIAID NIH HHS/United States
GR  - U01 AI035039/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180104
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (HLA Antigens)
RN  - 0 (KLRC1 protein, human)
RN  - 0 (Ligands)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily C)
RN  - 0 (Protein Sorting Signals)
SB  - IM
EIN - Science. 2019 Aug 2;365(6452):. PMID: 31371579
MH  - Alleles
MH  - CD4 Lymphocyte Count
MH  - Cohort Studies
MH  - HIV/*immunology
MH  - HIV Infections/drug therapy/genetics/*immunology
MH  - HLA Antigens/genetics/*metabolism
MH  - Humans
MH  - Killer Cells, Natural/*immunology
MH  - Ligands
MH  - NK Cell Lectin-Like Receptor Subfamily C/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Protein Sorting Signals
MH  - Viremia/immunology
PMC - PMC5933048
MID - NIHMS949646
EDAT- 2018/01/06 06:00
MHDA- 2018/04/11 06:00
PMCR- 2018/07/05
CRDT- 2018/01/06 06:00
PHST- 2017/01/30 00:00 [received]
PHST- 2017/10/16 00:00 [revised]
PHST- 2017/12/04 00:00 [accepted]
PHST- 2018/01/06 06:00 [entrez]
PHST- 2018/01/06 06:00 [pubmed]
PHST- 2018/04/11 06:00 [medline]
PHST- 2018/07/05 00:00 [pmc-release]
AID - 359/6371/86 [pii]
AID - 10.1126/science.aam8825 [doi]
PST - ppublish
SO  - Science. 2018 Jan 5;359(6371):86-90. doi: 10.1126/science.aam8825. Epub 2018 Jan 
      4.