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Journal article
Alprazolam Prompts HIV-1 Transcriptional Reactivation and Enhances CTL Response Through RUNX1 Inhibition and STAT5 Activation
Frontiers in neurology, v 12, pp 663793-663793
22 Jul 2021
PMID: 34367046
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The HIV-1 pandemic is a significant challenge to the field of medicine. Despite advancements in antiretroviral (ART) development, 38 million people worldwide still live with this disease without a cure. A significant barrier to the eradication of HIV-1 lies in the persistently latent pool that establishes early in the infection. The "shock and kill " strategy relies on the discovery of a latency-reversing agent (LRA) that can robustly reactivate the latent pool and not limit immune clearance. We have found that a benzodiazepine (BDZ), that is commonly prescribed for panic and anxiety disorder, to be an ideal candidate for latency reversal. The BDZ Alprazolam functions as an inhibitor of the transcription factor RUNX1, which negatively regulates HIV-1 transcription. In addition to the displacement of RUNX1 from the HIV-1 5'LTR, Alprazolam potentiates the activation of STAT5 and its recruitment to the viral promoter. The activation of STAT5 in cytotoxic T cells may enable immune activation which is independent of the IL-2 receptor. These findings have significance for the potential use of Alprazolam in a curative strategy and to addressing the neuroinflammation associated with neuroHIV-1.
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Details
- Title
- Alprazolam Prompts HIV-1 Transcriptional Reactivation and Enhances CTL Response Through RUNX1 Inhibition and STAT5 Activation
- Creators
- Angel Lin - Department of Biological Sciences, University of the Sciences, United StatesWeam Othman Elbezanti - University of PennsylvaniaAlexis Schirling - Department of Biological Sciences, University of the Sciences, United StatesAdel Ahmed - Drexel Univ, Dept Biochem & Mol Biol, Coll Med, Philadelphia, PA 19104 USARachel Van Duyne - Drexel UniversitySimon Cocklin - Drexel UniversityZachary Klase - Drexel University
- Publication Details
- Frontiers in neurology, v 12, pp 663793-663793
- Publisher
- Frontiers Media S.A.
- Number of pages
- 15
- Grant note
- DP2 DA044550-01 / NIDA/NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) Drexel University College of Medicine internal funds R01 AI150491 / NIAID/NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Pharmacology and Physiology
- Web of Science ID
- WOS:000687981800001
- Scopus ID
- 2-s2.0-85112624414
- Other Identifier
- 991019169909104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Neurosciences