PMID- 24603468
OWN - NLM
STAT- MEDLINE
DCOM- 20141125
LR  - 20220311
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 10
IP  - 3
DP  - 2014 Mar
TI  - LILRB2 interaction with HLA class I correlates with control of HIV-1 infection.
PG  - e1004196
LID - 10.1371/journal.pgen.1004196 [doi]
LID - e1004196
AB  - Natural progression of HIV-1 infection depends on genetic variation in the human 
      major histocompatibility complex (MHC) class I locus, and the CD8+ T cell 
      response is thought to be a primary mechanism of this effect. However, 
      polymorphism within the MHC may also alter innate immune activity against human 
      immunodeficiency virus type 1 (HIV-1) by changing interactions of human leukocyte 
      antigen (HLA) class I molecules with leukocyte immunoglobulin-like receptors 
      (LILR), a group of immunoregulatory receptors mainly expressed on myelomonocytic 
      cells including dendritic cells (DCs). We used previously characterized HLA 
      allotype-specific binding capacities of LILRB1 and LILRB2 as well as data from a 
      large cohort of HIV-1-infected individuals (N = 5126) to test whether LILR-HLA 
      class I interactions influence viral load in HIV-1 infection. Our analyses in 
      persons of European descent, the largest ethnic group examined, show that the 
      effect of HLA-B alleles on HIV-1 control correlates with the binding strength 
      between corresponding HLA-B allotypes and LILRB2 (p = 10(-2)). Moreover, overall 
      binding strength of LILRB2 to classical HLA class I allotypes, defined by the 
      HLA-A/B/C genotypes in each patient, positively associates with viral replication 
      in the absence of therapy in patients of both European (p = 10(-11)-10(-9)) and 
      African (p = 10(-5)-10(-3)) descent. This effect appears to be driven by 
      variations in LILRB2 binding affinities to HLA-B and is independent of individual 
      class I allelic effects that are not related to the LILRB2 function. 
      Correspondingly, in vitro experiments suggest that strong LILRB2-HLA binding 
      negatively affects antigen-presenting properties of DCs. Thus, we propose an 
      impact of LILRB2 on HIV-1 disease outcomes through altered regulation of DCs by 
      LILRB2-HLA engagement.
FAU - Bashirova, Arman A
AU  - Bashirova AA
AD  - Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos 
      Biomedical Research Inc., Frederick National Laboratory for Cancer Research, 
      Frederick, Maryland, United States of America; Ragon Institute of MGH, MIT and 
      Harvard, Boston, Massachusetts, United States of America.
FAU - Martin-Gayo, Enrique
AU  - Martin-Gayo E
AD  - Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of 
      America.
FAU - Jones, Des C
AU  - Jones DC
AD  - Department of Pathology, Cambridge University, Cambridge, United Kingdom.
FAU - Qi, Ying
AU  - Qi Y
AD  - Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos 
      Biomedical Research Inc., Frederick National Laboratory for Cancer Research, 
      Frederick, Maryland, United States of America.
FAU - Apps, Richard
AU  - Apps R
AD  - Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos 
      Biomedical Research Inc., Frederick National Laboratory for Cancer Research, 
      Frederick, Maryland, United States of America.
FAU - Gao, Xiaojiang
AU  - Gao X
AD  - Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos 
      Biomedical Research Inc., Frederick National Laboratory for Cancer Research, 
      Frederick, Maryland, United States of America.
FAU - Burke, Patrick S
AU  - Burke PS
AD  - Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of 
      America.
FAU - Taylor, Craig J
AU  - Taylor CJ
AD  - Tissue Typing Laboratories, Addenbrookes Hospital, Cambridge, United Kingdom.
FAU - Rogich, Jerome
AU  - Rogich J
AD  - Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of 
      America.
FAU - Wolinsky, Steven
AU  - Wolinsky S
AD  - Northwestern University Medical School, Chicago, Illinois, United States of 
      America.
FAU - Bream, Jay H
AU  - Bream JH
AD  - Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg 
      School of Public Health, Baltimore, Maryland, United States of America.
FAU - Duggal, Priya
AU  - Duggal P
AD  - Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg 
      School of Public Health, Baltimore, Maryland, United States of America.
FAU - Hussain, Shehnaz
AU  - Hussain S
AD  - Fielding School of Public Health, University of California at Los Angeles, Los 
      Angeles, California, United States of America.
FAU - Martinson, Jeremy
AU  - Martinson J
AD  - University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
FAU - Weintrob, Amy
AU  - Weintrob A
AD  - USU Infectious Disease Clinical Research Program, Bethesda, Maryland, United 
      States of America.
FAU - Kirk, Gregory D
AU  - Kirk GD
AD  - Johns Hopkins University School of Public Health, Baltimore, Maryland, United 
      States of America.
FAU - Fellay, Jacques
AU  - Fellay J
AD  - School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne, 
      Switzerland.
FAU - Buchbinder, Susan P
AU  - Buchbinder SP
AD  - San Francisco Department of Public Health, San Francisco, California, United 
      States of America.
FAU - Goedert, James J
AU  - Goedert JJ
AD  - Division of Cancer Epidemiology & Genetics, NCI, Bethesda, Maryland, United 
      States of America.
FAU - Deeks, Steven G
AU  - Deeks SG
AD  - University of California at San Francisco Medical School, San Francisco, 
      California, United States of America.
FAU - Pereyra, Florencia
AU  - Pereyra F
AD  - Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of 
      America; Infectious Disease Division, Brigham and Women's Hospital, Boston, 
      Massachusetts, United States of America.
FAU - Trowsdale, John
AU  - Trowsdale J
AD  - Department of Pathology, Cambridge University, Cambridge, United Kingdom.
FAU - Lichterfeld, Mathias
AU  - Lichterfeld M
AD  - Infectious Disease Division, Massachusetts General Hospital, Boston, 
      Massachusetts, United States of America.
FAU - Telenti, Amalio
AU  - Telenti A
AD  - Institute of Microbiology, University Hospital and University of Lausanne, 
      Lausanne, Switzerland.
FAU - Walker, Bruce D
AU  - Walker BD
AD  - Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of 
      America; Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of 
      America.
FAU - Allen, Rachel L
AU  - Allen RL
AD  - St George's Medical School, University of London, London, United Kingdom.
FAU - Carrington, Mary
AU  - Carrington M
AD  - Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos 
      Biomedical Research Inc., Frederick National Laboratory for Cancer Research, 
      Frederick, Maryland, United States of America; Ragon Institute of MGH, MIT and 
      Harvard, Boston, Massachusetts, United States of America.
FAU - Yu, Xu G
AU  - Yu XG
AD  - Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of 
      America.
LA  - eng
GR  - P30 MH062246/MH/NIMH NIH HHS/United States
GR  - R01 AI078799/AI/NIAID NIH HHS/United States
GR  - UL1 RR025005/RR/NCRR NIH HHS/United States
GR  - G0901682/MRC_/Medical Research Council/United Kingdom
GR  - R56 AI098484/AI/NIAID NIH HHS/United States
GR  - UL1 RR024131/RR/NCRR NIH HHS/United States
GR  - U01-AI-35041/AI/NIAID NIH HHS/United States
GR  - UM1 AI035043/AI/NIAID NIH HHS/United States
GR  - R01 AI087145/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 AI035043/AI/NIAID NIH HHS/United States
GR  - U01 AI035040/AI/NIAID NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - U01 AI035042/AI/NIAID NIH HHS/United States
GR  - U01 DA036297/DA/NIDA NIH HHS/United States
GR  - R01 AI087452/AI/NIAID NIH HHS/United States
GR  - U01-AI-35043/AI/NIAID NIH HHS/United States
GR  - 13-0074/AICR_/Worldwide Cancer Research/United Kingdom
GR  - U01-AI-35042/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - K24 AI069994/AI/NIAID NIH HHS/United States
GR  - U01 AI035041/AI/NIAID NIH HHS/United States
GR  - R24 AI067039/AI/NIAID NIH HHS/United States
GR  - UL1-RR025005/RR/NCRR NIH HHS/United States
GR  - U01-AI-35040/AI/NIAID NIH HHS/United States
GR  - Wellcome Trust/United Kingdom
GR  - U01-AI-35039/AI/NIAID NIH HHS/United States
GR  - R01 DA012568/DA/NIDA NIH HHS/United States
GR  - NIH/NIAID R01 AI078799/PHS HHS/United States
GR  - 100140/Wellcome Trust/United Kingdom
GR  - R01 AI089339/AI/NIAID NIH HHS/United States
GR  - P30 MH62246/MH/NIMH NIH HHS/United States
GR  - U01 AI035039/AI/NIAID NIH HHS/United States
GR  - P30 AI060354/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 - 20140306
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (LILRB2 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Alleles
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Dendritic Cells/immunology
MH  - Female
MH  - HIV Infections/genetics/*immunology/virology
MH  - HIV-1/genetics/immunology
MH  - Histocompatibility Antigens Class I/genetics/*immunology
MH  - Humans
MH  - Immunity, Innate/*genetics
MH  - Membrane Glycoproteins/*genetics/immunology
MH  - Receptors, Immunologic/*genetics/immunology
MH  - Viral Load/genetics/immunology
PMC - PMC3945438
COIS- The authors have declared that no competing interests exist.
EDAT- 2014/03/08 06:00
MHDA- 2014/12/15 06:00
PMCR- 2014/03/06
CRDT- 2014/03/08 06:00
PHST- 2013/04/09 00:00 [received]
PHST- 2013/12/25 00:00 [accepted]
PHST- 2014/03/08 06:00 [entrez]
PHST- 2014/03/08 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
PHST- 2014/03/06 00:00 [pmc-release]
AID - PGENETICS-D-13-00955 [pii]
AID - 10.1371/journal.pgen.1004196 [doi]
PST - epublish
SO  - PLoS Genet. 2014 Mar 6;10(3):e1004196. doi: 10.1371/journal.pgen.1004196. 
      eCollection 2014 Mar.