Epistatic Interaction Between KIR3DS1 and HLA-B Delays the Progression to AIDS

Authors

• Maureen P. Martin, National Cancer Institute at Frederick
• Xiaojiang Gao, National Cancer Institute at Frederick
• Jeong-Hee Lee, National Cancer Institute at Frederick
• George W. Nelson, National Cancer Institute at Frederick
• Roger Detels, University of California - Los Angeles
• James J. Goedert, National Cancer Institute at Bethesda
• Susan Buchbinder, San Francisco Department of Public Health
• Keith Hoots, University of Texas Health Science Center at Houston
• David Vlahov, Johns Hopkins School of Hygiene and Public Health
• John Trowsdale, University of Cambridge - United Kingdom
• Michael Wilson, University of Cambridge - United Kingdom
• Stephen J. O'Brien, National Cancer Institute at FrederickFollow
• Mary Carrington, National Cancer Institute at Frederick

ORCID

0000-0001-7353-8301

ResearcherID

N-1726-2015

Document Type

Article

Publication Title

Nature Genetics

ISSN

1061-4036

Publication Date

8-2002

Abstract

Natural killer (NK) cells provide defense in the early stages of the innate immune response against viral infections by producing cytokines and causing cytotoxicity. The killer immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of human leukocyte antigen (HLA) class I molecules on target cells. KIR and HLA loci are both highly polymorphic, and some HLA class I products bind and trigger cell-surface receptors specified by KIR genes. Here we report that the activating KIR allele KIR3DS1, in combination with HLA-B alleles that encode molecules with isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed progression to AIDS in individuals infected with human immunodeficiency virus type 1 (HIV-1). In the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated with any of the AIDS outcomes measured. By contrast, in the absence of HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more rapid progression to AIDS. These observations are strongly suggestive of a model involving an epistatic interaction between the two loci. The strongest synergistic effect of these loci was on progression to depletion of CD4⁺ T cells, which suggests that a protective response of NK cells involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1 infection.

Volume

31

Issue

4

First Page

429

Last Page

434

Comments

©2002 Nature Publishing Group

NSUWorks Citation

Martin, Maureen P.; Xiaojiang Gao; Jeong-Hee Lee; George W. Nelson; Roger Detels; James J. Goedert; Susan Buchbinder; Keith Hoots; David Vlahov; John Trowsdale; Michael Wilson; Stephen J. O'Brien; and Mary Carrington. 2002. "Epistatic Interaction Between KIR3DS1 and HLA-B Delays the Progression to AIDS." Nature Genetics 31, (4): 429-434. https://nsuworks.nova.edu/cnso_bio_facarticles/590