Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes.
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.
Alter
Galit
G
Partners AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Boston, MA 02129, USA.
Martin
Maureen P
MP
Teigen
Nickolas
N
Carr
William H
WH
Suscovich
Todd J
TJ
Schneidewind
Arne
A
Streeck
Hendrik
H
Waring
Michael
M
Meier
Angela
A
Brander
Christian
C
Lifson
Jeffrey D
JD
Allen
Todd M
TM
Carrington
Mary
M
Altfeld
Marcus
M
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*
D006680:HLA Antigens; D054340:Receptors, KIR