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

PLoS ONE, ISSN: 1932-6203, Vol: 9, Issue: 6, Page: e99353
2014
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Article Description

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. © 2014 Merino et al.

Bibliographic Details

http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84902436694&origin=inward; http://dx.doi.org/10.1371/journal.pone.0099353; http://www.ncbi.nlm.nih.gov/pubmed/24901871; https://dx.plos.org/10.1371/journal.pone.0099353.g003; http://dx.doi.org/10.1371/journal.pone.0099353.g003; https://dx.plos.org/10.1371/journal.pone.0099353.g001; http://dx.doi.org/10.1371/journal.pone.0099353.g001; https://dx.plos.org/10.1371/journal.pone.0099353; https://dx.plos.org/10.1371/journal.pone.0099353.t002; http://dx.doi.org/10.1371/journal.pone.0099353.t002; https://dx.plos.org/10.1371/journal.pone.0099353.t001; http://dx.doi.org/10.1371/journal.pone.0099353.t001; https://dx.plos.org/10.1371/journal.pone.0099353.g002; http://dx.doi.org/10.1371/journal.pone.0099353.g002; https://dx.doi.org/10.1371/journal.pone.0099353.g003; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0099353.g003; https://dx.doi.org/10.1371/journal.pone.0099353.g002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0099353.g002; https://dx.doi.org/10.1371/journal.pone.0099353; https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099353; https://dx.doi.org/10.1371/journal.pone.0099353.g001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0099353.g001; https://dx.doi.org/10.1371/journal.pone.0099353.t002; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0099353.t002; https://dx.doi.org/10.1371/journal.pone.0099353.t001; https://journals.plos.org/plosone/article/figure?id=10.1371/journal.pone.0099353.t001; http://dx.plos.org/10.1371/journal.pone.0099353.g002; http://dx.plos.org/10.1371/journal.pone.0099353.g003; http://dx.plos.org/10.1371/journal.pone.0099353.t002; http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0099353; https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0099353&type=printable; http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0099353; http://dx.plos.org/10.1371/journal.pone.0099353.t001; http://dx.plos.org/10.1371/journal.pone.0099353; http://www.plosone.org/article/metrics/info:doi/10.1371/journal.pone.0099353; http://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0099353&type=printable; http://dx.plos.org/10.1371/journal.pone.0099353.g001

Aimee M. Merino; Anne-Sophie Dugast; Craig M. Wilson; Paul A. Goepfert; Galit Alter; Richard A. Kaslow; Jianming Tang; Derya Unutmaz

Public Library of Science (PLoS)

Multidisciplinary

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