KIR2DS4 promotes HIV-1 pathogenesis: New evidence from analyses of immunogenetic data and natural killer cell function

Aimee M. Merino, Anne Sophie Dugast, Craig M. Wilson, Paul A. Goepfert, Galit Alter, Richard A. Kaslow, Jianming Tang

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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. Methodology/Principal Findings: 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/Significance: Full-length KIR2DS4 promotes HIV-1 pathogenesis during chronic infection, probably through the maintenance of an excessively pro-inflammatory state.

Original languageEnglish (US)
Article numbere99353
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 5 2014

Fingerprint Dive into the research topics of 'KIR2DS4 promotes HIV-1 pathogenesis: New evidence from analyses of immunogenetic data and natural killer cell function'. Together they form a unique fingerprint.

Cite this