Expression from the HIV-1 LTR can be repressed in a small population of cells, Martini Glasses 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 Swing Arm 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.