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2018 ; 14
(3
): e1006950
Nephropedia Template TP
Contreras X
; Salifou K
; Sanchez G
; Helsmoortel M
; Beyne E
; Bluy L
; Pelletier S
; Rousset E
; Rouquier S
; Kiernan R
PLoS Pathog
2018[Mar]; 14
(3
): e1006950
PMID29554134
show ga
Expression from the HIV-1 LTR can be repressed in a small population of cells,
which contributes to the latent reservoir. The factors mediating this repression
have not been clearly elucidated. We have identified a network of nuclear RNA
surveillance factors that act as effectors of HIV-1 silencing. RRP6, MTR4, ZCCHC8
and ZFC3H1 physically associate with the HIV-1 TAR region and repress
transcriptional output and recruitment of RNAPII to the LTR. Knock-down of these
factors in J-Lat cells increased the number of GFP-positive cells, with a
concomitant increase in histone marks associated with transcriptional activation.
Loss of these factors increased HIV-1 expression from infected PBMCs and led to
reactivation of HIV-1 from latently infected PBMCs. These findings identify a
network of novel transcriptional repressors that control HIV-1 expression and
which could open new avenues for therapeutic intervention.