NUCLEAR RNA SURVEILLANCE COMPLEXES SILENCE HIV-1 TRANSCRIPTION.

Nuclear RNA surveillance complexes silence HIV-1 transcription.

Nuclear RNA surveillance complexes silence HIV-1 transcription.

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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 Fridge Handle Set 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 Spike open new avenues for therapeutic intervention.

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