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Article Dans Une Revue PLoS Pathogens Année : 2018

Nuclear RNA surveillance complexes silence HIV-1 transcription

Résumé

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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hal-01741841 , version 1 (01-06-2021)

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Xavier Contreras, Kader Salifou, Gabriel Sanchez, Marion Helsmoortel, Emmanuelle Beyne, et al.. Nuclear RNA surveillance complexes silence HIV-1 transcription. PLoS Pathogens, 2018, 14 (3), pp.e1006950. ⟨10.1371/journal.ppat.1006950⟩. ⟨hal-01741841⟩
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