Modulation of BRD4 in HIV epigenetic regulation: implications for finding an HIV cure

Retrovirology. 2021 Jan 7;18(1):3. doi: 10.1186/s12977-020-00547-9.

Abstract

Following reverse transcription, HIV viral DNA is integrated into host cell genomes and establishes a stable latent infection, which has posed a major obstacle for obtaining a cure for HIV. HIV proviral transcription is regulated in cellular reservoirs by complex host epigenetic and transcriptional machineries. The Bromodomain (BD) and Extra-Terminal Domain (ET) protein, BRD4, is an important epigenetic reader that interacts with acetyl-histones and a variety of chromatin and transcriptional regulators to control gene expression, including HIV. Modulation of BRD4 by a pan BET inhibitor (JQ1) has been shown to activate HIV transcription. Recent studies by my group and others indicate that the function of BRD4 is versatile and its effects on HIV transcription may depend on the partner proteins or pathways engaged by BRD4. Our studies have reported a novel class of small-molecule modulators that are distinct from JQ1 but induce HIV transcriptional suppression through BRD4. Herein, we reviewed recent research on the modulation of BRD4 in HIV epigenetic regulation and discussed their potential implications for finding an HIV cure.

Keywords: BRD4; Epigenetic regulation; HIV; Latency.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Cycle Proteins / genetics*
  • Epigenesis, Genetic / drug effects*
  • Gene Expression Regulation*
  • HIV / drug effects
  • HIV Infections / drug therapy*
  • HIV Infections / genetics*
  • Humans
  • Small Molecule Libraries / pharmacology
  • Transcription Factors / genetics*

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • Small Molecule Libraries
  • Transcription Factors