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Nuclear RNA surveillance complexes silence HIV-1 transcription

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Contreras, Xavier | Salifou, Kader | Sanchez, Gabriel | Helsmoortel, Marion | Beyne, Emmanuelle | Bluy, Lisa | Pelletier, Stéphane | Rousset, Emilie | Rouquier, Sylvie | Kiernan, Rosemary

Edité par CCSD ; Public Library of Science -

International audience. 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.

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