KIR2DS4 Promotes HIV-1 Pathogenesis: New Evidence from Analyses of Immunogenetic Data and Natural Killer Cell Function
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Merino-2014-KIR2DS4 Promotes HIV.pdf
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Author(s)
Merino, Aimee M.
Dugast, Anne-Sophie
Wilson, Craig M.
Goepfert, Paul A.
Alter, Galit
Kaslow, Richard A.
Tang, Jianming
Date Issued
June 2014
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Merino, Aimee M., Anne-Sophie Dugast, Craig M. Wilson, Paul A. Goepfert, Galit Alter, Richard A. Kaslow, and Jianming Tang. “KIR2DS4 Promotes HIV-1 Pathogenesis: New Evidence from Analyses of Immunogenetic Data and Natural Killer Cell Function.” Edited by Derya Unutmaz. PLoS ONE 9, no. 6 (June 5, 2014): e99353.
Version
Final published version
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[superscript +] 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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Ragon Institute of MGH, MIT and Harvard
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DOI of Published Version
https://doi.org/10.1371/journal.pone.0099353
