Nuclear RNA surveillance complexes silence HIV-1 transcription.
Autor: | Xavier Contreras, Kader Salifou, Gabriel Sanchez, Marion Helsmoortel, Emmanuelle Beyne, Lisa Bluy, Stéphane Pelletier, Emilie Rousset, Sylvie Rouquier, Rosemary Kiernan |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: | |
Zdroj: | PLoS Pathogens, Vol 14, Iss 3, p e1006950 (2018) |
Druh dokumentu: | article |
ISSN: | 1553-7366 1553-7374 |
DOI: | 10.1371/journal.ppat.1006950 |
Popis: | 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. |
Databáze: | Directory of Open Access Journals |
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