KIR2DS4 promotes HIV-1 pathogenesis: new evidence from analyses of immunogenetic data and natural killer cell function.
PLoS One
; 9(6): e99353, 2014.
Article
en En
| MEDLINE
| ID: mdl-24901871
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/PRINCIPALFINDINGS:
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-1ß. 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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Infecciones por VIH
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VIH-1
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Receptores KIR
Tipo de estudio:
Etiology_studies
/
Observational_studies
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Prevalence_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2014
Tipo del documento:
Article