title: KIR2DS4 promotes HIV-1 pathogenesis: new evidence from analyses of immunogenetic data and natural killer cell function.
abstract: BACKGROUND
  KIR2DS4 gene variants encode full-length and truncated protein products, with only the former serving as membrane-bound receptors to activate natural killer (NK) cells. We have previously shown that full-length KIR2DS4 was associated with relatively high viral load and accelerated heterosexual HIV-1 transmission. Our objective here was to provide confirmatory data and to offer new insights about the potential mechanisms.
  
  
  RESULTS
  Mixed models for repeated (longitudinal) outcome measurements on 207 HIV-1 seropositive American youth revealed an association of full-length KIR2DS4 with relatively high viral load and low CD4+ T-cell count (p<0.01 for both). Depending on KIR2DS4 expression (presence or absence) on cell surface, NK cells from 43 individuals with untreated, chronic HIV-1 infection often differed in functional properties, including degranulation and secretion of IFN-γ and MIP-1β. In particular, polyfunctional NK cells were enriched in the KIR2DS4-positive subset.
  
  
  CONCLUSIONS
  Full-length KIR2DS4 promotes HIV-1 pathogenesis during chronic infection, probably through the maintenance of an excessively pro-inflammatory state.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Merino
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Dugast
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Craig M
authors.initials: CM
authors.lastname: Wilson
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Boston, Massachusetts, United States of America.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
mesh_terms: D000293:Adolescent; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity*; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D054340:Receptors, KIR / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load; D055815:Young Adult
chemical_list: D006680:HLA Antigens; C473953:KIR2DS4 protein, human; D054340:Receptors, KIR