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: Galit Alter, Maureen P Martin, Nickolas Teigen, William H Carr, Todd J Suscovich, Arne Schneidewind, Hendrik Streeck, Michael Waring, Angela Meier, Christian Brander, Jeffrey D Lifson, Todd M Allen, Mary Carrington, Marcus Altfeld
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 204 Issue 12 Pg. 3027-36 (Nov 26 2007) ISSN: 1540-9538 [Electronic] United States
• PMID: 18025129 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• HLA Antigens
• Receptors, KIR

Topics

• CD4-Positive T-Lymphocytes (immunology, virology)
• HIV Infections (immunology)
• HIV-1 (physiology)
• HLA Antigens (immunology)
• Humans
• Killer Cells, Natural (immunology, virology)
• Kinetics
• Receptors, KIR (genetics, immunology)
• Virus Replication (physiology)