Viruses, Vol. 12, Pages 191: Benzodiazepines Drive Alteration of Chromatin at the Integrated HIV-1 LTR

Viruses, Vol. 12, Pages 191: Benzodiazepines Drive Alteration of Chromatin at the Integrated HIV-1 LTR Viruses doi: 10.3390/v12020191 Authors: Weam Elbezanti Angel Lin Alexis Schirling Alexandria Jackson Matthew Marshall Rachel Van Duyne Frank Maldarelli Luca Sardo Zachary Klase Antiretroviral therapy (ART) lowers human immunodeficiency virus type 1 (HIV-1) viral load to undetectable levels, but does not eliminate the latent reservoir. One of the factors controlling the latent reservoir is transcriptional silencing of the integrated HIV-1 long terminal repeat (LTR). The molecular mechanisms that control HIV-1 transcription are not completely understood. We have previously shown that RUNX1, a host transcription factor, may play a role in the establishment and maintenance of HIV-1 latency. Prior work has demonstrated that inhibition of RUNX1 by the benzodiazepine (BDZ) Ro5-3335 synergizes with suberanilohydroxamic acid (SAHA) to activate HIV-1 transcription. In this current work, we examine the effect of RUNX1 inhibition on the chromatin state of the integrated HIV-1 LTR. Using chromatin immunoprecipitation (ChIP), we found that Ro5-3335 significantly increased the occupancy of STAT5 at the HIV-1 LTR. We also screened other BDZs for their ability to regulate HIV-1 transcription and demonstrate their ability to increase transcription and alter chromatin at the LTR without negatively affecting Tat activity. These findings shed further light on the mechanis...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
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