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Elife ; 82019 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-30964004

RESUMEN

HIV +Elite and Viremic controllers (EC/VCs) are able to control virus infection, perhaps because of host genetic determinants. We identified 16% (21 of 131) EC/VCs with CD4 +T cells with resistance specific to R5-tropic HIV, reversed after introduction of ccr5. R5 resistance was not observed in macrophages and depended upon the method of T cell activation. CD4 +T cells of these EC/VCs had lower ccr2 and ccr5 RNA levels, reduced CCR2 and CCR5 cell-surface expression, and decreased levels of secreted chemokines. T cells had no changes in chemokine receptor mRNA half-life but instead had lower levels of active transcription of ccr2 and ccr5, despite having more accessible chromatin by ATAC-seq. Other nearby genes were also down-regulated, over a region of ~500 kb on chromosome 3p21. This same R5 resistance phenotype was observed in family members of an index VC, also associated with ccr2/ccr5 down-regulation, suggesting that the phenotype is heritable.


Asunto(s)
Resistencia a la Enfermedad , Regulación hacia Abajo , Familia , Infecciones por VIH/inmunología , Sobrevivientes de VIH a Largo Plazo , Receptores CCR5/biosíntesis , Adulto , Anciano , Linfocitos T CD4-Positivos/química , Linfocitos T CD4-Positivos/virología , Células Cultivadas , Femenino , VIH-1/crecimiento & desarrollo , Humanos , Macrófagos/química , Macrófagos/virología , Masculino , Persona de Mediana Edad , Receptores CCR2/biosíntesis , Tropismo Viral , Adulto Joven
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