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KIR2DS4 Promotes HIV-1 Pathogenesis: New Evidence from Analyses of Immunogenetic Data and Natural Killer Cell Function

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 hetero...

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Detalles Bibliográficos
Autores principales: Merino, Aimee M., Dugast, Anne-Sophie, Wilson, Craig M., Goepfert, Paul A., Alter, Galit, Kaslow, Richard A., Tang, Jianming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047121/
https://www.ncbi.nlm.nih.gov/pubmed/24901871
http://dx.doi.org/10.1371/journal.pone.0099353
Descripción
Sumario: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.