Are BET inhibitors yet promising latency-reversing agents for HIV-1 reactivation in AIDS therapy?

Salahong, T., Schwartz, C. and Sungthong, R. (2021) Are BET inhibitors yet promising latency-reversing agents for HIV-1 reactivation in AIDS therapy? Viruses, 13(6), 1026. (doi: 10.3390/v13061026) (PMID:34072421) (PMCID:PMC8228869)

Abstract

AIDS first emerged decades ago; however, its cure, i.e., eliminating all virus sources, is still unachievable. A critical burden of AIDS therapy is the evasive nature of HIV-1 in face of host immune responses, the so-called “latency.” Recently, a promising approach, the “Shock and Kill” strategy, was proposed to eliminate latently HIV-1-infected cell reservoirs. The “Shock and Kill” concept involves two crucial steps: HIV-1 reactivation from its latency stage using a latency-reversing agent (LRA) followed by host immune responses to destroy HIV-1-infected cells in combination with reinforced antiretroviral therapy to kill the progeny virus. Hence, a key challenge is to search for optimal LRAs. Looking at epigenetics of HIV-1 infection, researchers proved that some bromodomains and extra-terminal motif protein inhibitors (BETis) are able to reactivate HIV-1 from latency. However, to date, only a few BETis have shown HIV-1-reactivating functions, and none of them have yet been approved for clinical trial. In this review, we aim to demonstrate the epigenetic roles of BETis in HIV-1 infection and HIV-1-related immune responses. Possible future applications of BETis and their HIV-1-reactivating properties are summarized and discussed.

• Item Type: Articles
• Additional Information: This research received no external funding. During preparation of the manuscript, T.S. had funding support from the Junior Science Talent Project (JSTP)–National Science and Tech-nology Development Agency, Pathumthani, Thailand, and R.S. had financial support from the UK Medical Research Council (Confidence in Concept Award: MRC/Strep POC 304737-01).
• Keywords: HIV-1, latently HIV-1-infected cell, latency-reversing agent, BET protein, BRD2, BRD4, LRA, BETi, epigenetics, immune response.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sungthong, Dr Rungroch

Creator Roles

Sungthong, R.: Conceptualization, Writing – review and editing, Supervision, Funding acquisition

• Authors: Salahong, T., Schwartz, C., and Sungthong, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Viruses
• Publisher: MDPI
• ISSN: 1999-4915
• ISSN (Online): 1999-4915
• Published Online: 29 May 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Viruses 13(6): 1026
• Publisher Policy: Reproduced under a Creative Commons License