title: Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes.
abstract: Decline of peak viremia during acute HIV-1 infection occurs before the development of vigorous adaptive immunity, and the level of decline correlates inversely with the rate of AIDS progression, implicating a potential role for the innate immune response in determining disease outcome. The combined expression of an activating natural killer (NK) cell receptor, the killer immunoglobulin-like receptor (KIR) 3DS1, and its presumed ligand, human leukocyte antigen (HLA)-B Bw4-80I, has been associated in epidemiological studies with a slow progression to AIDS. We examined the functional ability of NK cells to differentially control HIV-1 replication in vitro based on their KIR and HLA types. NK cells expressing KIR3DS1 showed strong, significant dose- and cell contact-dependent inhibition of HIV-1 replication in target cells expressing HLA-B Bw4-80I compared with NK cells that did not express KIR3DS1. Furthermore, KIR3DS1+ NK cells and NKLs were preferentially activated, and lysed HIV-1 infected target cells in an HLA-B Bw4-80I-dependent manner. These data provide the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication.
authors.affiliation: Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.forename: Maureen P
authors.initials: MP
authors.lastname: Martin
authors.forename: Nickolas
authors.initials: N
authors.lastname: Teigen
authors.forename: William H
authors.initials: WH
authors.lastname: Carr
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Suscovich
authors.forename: Arne
authors.initials: A
authors.lastname: Schneidewind
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.forename: Michael
authors.initials: M
authors.lastname: Waring
authors.forename: Angela
authors.initials: A
authors.lastname: Meier
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology*; D007700:Kinetics; D054340:Receptors, KIR / Q000235:genetics* / Q000276:immunology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR