Journal article
Benzodiazepines Drive Alteration of Chromatin at the Integrated HIV-1 LTR
Viruses, v 12(2), p191
09 Feb 2020
PMID: 32050449
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 mechanism by which RUNX proteins control HIV-1 transcription and suggest that BDZ compounds might be useful in activating HIV-1 transcription through STAT5 recruitment to the HIV-1 LTR.
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Details
- Title
- Benzodiazepines Drive Alteration of Chromatin at the Integrated HIV-1 LTR
- Creators
- Weam Elbezanti - University of the SciencesAngel Lin - University of the SciencesAlexis Schirling - University of the SciencesAlexandria Jackson - University of the SciencesMatthew Marshall - Univ Sci, Dept Biol Sci, Philadelphia, PA 19104 USARachel Van Duyne - University of the SciencesFrank Maldarelli - Center for Cancer ResearchLuca Sardo - United States Military AcademyZachary Klase - University of the Sciences
- Publication Details
- Viruses, v 12(2), p191
- Publisher
- Mdpi
- Number of pages
- 16
- Grant note
- University of the Sciences W. W. Smith Charitable Trust 1DP2DA044550 / National Institutes of Health (NIH)/NIDA Avenir award; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000521256600072
- Scopus ID
- 2-s2.0-85079336272
- Other Identifier
- 991021902507904721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Virology