Bromodomain Proteins in HIV Infection

Bromodomains are conserved protein modules of ~110 amino acids that bind acetylated lysine residues in histone and non-histone proteins. Bromodomains are present in many chromatin-associated transcriptional regulators and have been linked to diverse aspects of the HIV life cycle, including transcription and integration. Here, we review the role of bromodomain-containing proteins in HIV infection. We begin with a focus on acetylated viral factors, followed by a discussion of structural and biological studies defining the involvement of bromodomain proteins in the HIV life cycle. We end with an overview of promising new studies of bromodomain inhibitory compounds for the treatment of HIV latency.

• Publication year

  2013

• Venue

  Viruses

• Publication date

  2013-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/v5061571PMID 23793227PMCID 3717722
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Chromatin organization and transcriptional regulation.

  2013cited by this paper
• The search for an HIV cure: tackling latent infection.

  2013cited by this paper
• BET bromodomain-targeting compounds reactivate HIV from latency via a Tat-independent mechanism

  2013cited by this paper
• PCAF acetylates Runx2 and promotes osteoblast differentiation

  2013cited by this paper
• The BAF complex and HIV latency

  2012cited by this paper
• Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family

  2012cited by this paper
• Benzodiazepines and benzotriazepines as protein interaction inhibitors targeting bromodomains of the BET family

  2012cited by this paper
• The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation

  2012cited by this paper
• Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV‐1 reservoirs: results from a multicentre randomized clinical study

  2012cited by this paper
• BET bromodomain inhibition as a novel strategy for reactivation of HIV‐1

  2012cited by this paper
• Down-regulation of NF-κB Transcriptional Activity in HIV-associated Kidney Disease by BRD4 Inhibition*

  2012cited by this paper
• Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

  2012cited by this paper
• The bromodomain interaction module

  2012cited by this paper
• Design and Implementation of a Randomized Crossover Study of Valproic Acid and Antiretroviral Therapy to Reduce the HIV Reservoir

  2012cited by this paper
• Reactivation of latent HIV-1 by inhibition of BRD4.

  2012cited by this paper
• Bromodomain and Extra-terminal (BET) Bromodomain Inhibition Activate Transcription via Transient Release of Positive Transcription Elongation Factor b (P-TEFb) from 7SK Small Nuclear Ribonucleoprotein*

  2012cited by this paper
• HIV-1 Vif promotes the G₁- to S-phase cell-cycle transition.

  2011cited by this paper
• Analysis of the human endogenous coregulator complexome.

  2011cited by this paper
• Identification of cellular factors binding to acetylated HIV-1 integrase

  2011cited by this paper
• RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia

  2011cited by this paper
• Regulation of Tat Acetylation and Transactivation Activity by the Microtubule-associated Deacetylase HDAC6*

  2011cited by this paper
• Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia

  2011cited by this paper
• Two-pronged Binding with Bromodomain-containing Protein 4 Liberates Positive Transcription Elongation Factor b from Inactive Ribonucleoprotein Complexes*

  2011cited by this paper
• Repressive LTR Nucleosome Positioning by the BAF Complex Is Required for HIV Latency

  2011cited by this paper
• Regulation of chromatin by histone modifications

  2011cited by this paper
• Varying modulation of HIV-1 LTR activity by Baf complexes.

  2011cited by this paper
• The TRIM family protein KAP1 inhibits HIV-1 integration.

  2011cited by this paper
• HIV-1 Tat assembles a multifunctional transcription elongation complex and stably associates with the 7SK snRNP.

  2010cited by this paper
• HIV-1 Tat and host AFF4 recruit two transcription elongation factors into a bifunctional complex for coordinated activation of HIV-1 transcription.

  2010cited by this paper
• Transcription through the HIV-1 nucleosomes: effects of the PBAF complex in Tat activated transcription.

  2010cited by this paper
• PML Nuclear Body Component Sp140 Is a Novel Autoantigen in Primary Biliary Cirrhosis

  2010cited by this paper
• Selective inhibition of BET bromodomains

  2010cited by this paper
• Suppression of inflammation by a synthetic histone mimic

  2010cited by this paper
• Cooperative binding of two acetylation marks on a histone tail by a single bromodomain

  2009cited by this paper
• Structures of the Dual Bromodomains of the P-TEFb-activating Protein Brd4 at Atomic Resolution*

  2009cited by this paper
• Short communication: activation of latent HIV type 1 gene expression by suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor approved for use to treat cutaneous T cell lymphoma.

  2009cited by this paper
• GCN5-dependent acetylation of HIV-1 integrase enhances viral integration

  2009cited by this paper
• Acetylation of cyclin T1 regulates the equilibrium between active and inactive P‐TEFb in cells

  2009cited by this paper
• Suberoylanilide Hydroxamic Acid Reactivates HIV from Latently Infected Cells*

  2009cited by this paper
• Tat acetylation modulates assembly of a viral-host RNA–protein transcription complex

  2009cited by this paper
• Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions

  2009cited by this paper
• The Bromodomain Protein Brd4 Stimulates G1 Gene Transcription and Promotes Progression to S Phase*

  2008cited by this paper
• Lysine acetylation: codified crosstalk with other posttranslational modifications.

  2008cited by this paper
• Bromodomain Protein Brd4 Regulates Human Immunodeficiency Virus Transcription through Phosphorylation of CDK9 at Threonine 29

  2008cited by this paper
• Structural insights into human KAP1 PHD finger–bromodomain and its role in gene silencing

  2008cited by this paper
• c-Myc and Sp1 Contribute to Proviral Latency by Recruiting Histone Deacetylase 1 to the Human Immunodeficiency Virus Type 1 Promoter

  2007influential reference
• Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription

  2007cited by this paper
• Distinct GCN5/PCAF-containing complexes function as co-activators and are involved in transcription factor and global histone acetylation

  2007cited by this paper
• Brd4 Recruits P-TEFb to Chromosomes at Late Mitosis To Promote G1 Gene Expression and Cell Cycle Progression

  2007cited by this paper
• The Double Bromodomain-containing Chromatin Adaptor Brd4 and Transcriptional Regulation*

  2007cited by this paper
• CBF‐1 promotes transcriptional silencing during the establishment of HIV‐1 latency

  2007cited by this paper
• NF‐κB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation

  2006cited by this paper
• Transcriptional Repression of Human Immunodeficiency Virus Type 1 by AP-4*

  2006cited by this paper
• The SWI/SNF Chromatin-remodeling Complex Is a Cofactor for Tat Transactivation of the HIV Promoter*

  2006cited by this paper
• Identification of transcription complexes that contain the double bromodomain protein Brd2 and chromatin remodeling machines.

  2006cited by this paper
• Requirement for SWI/SNF chromatin‐remodeling complex in Tat‐mediated activation of the HIV‐1 promoter

  2006cited by this paper
• Acetylation of HIV‐1 integrase by p300 regulates viral integration

  2005cited by this paper
• Recruitment of P-TEFb for stimulation of transcriptional elongation by the bromodomain protein Brd4.

  2005cited by this paper
• SIRT1 Regulates HIV Transcription via Tat Deacetylation

  2005cited by this paper
• Selective small molecules blocking HIV-1 Tat and coactivator PCAF association.

  2005cited by this paper
• Acetylation of Tat defines a cyclinT1-independent step in HIV transactivation.

  2003cited by this paper
• The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif

  2003cited by this paper
• Phase I clinical trial of histone deacetylase inhibitor: suberoylanilide hydroxamic acid administered intravenously.

  2003cited by this paper
• Regulation of HIV‐1 gene expression by histone acetylation and factor recruitment at the LTR promoter

  2003influential reference
• The double bromodomain protein Brd4 binds to acetylated chromatin during interphase and mitosis

  2003cited by this paper
• Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators

  2002influential reference
• Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF bromodomain.

  2002cited by this paper
• Tat Acetyl-acceptor Lysines Are Important for Human Immunodeficiency Virus Type-1 Replication*

  2002cited by this paper
• Transcriptional synergy between Tat and PCAF is dependent on the binding of acetylated Tat to the PCAF bromodomain

  2002cited by this paper
• Implication of the Lymphocyte-Specific Nuclear Body Protein Sp140 in an Innate Response to Human Immunodeficiency Virus Type 1

  2002influential reference
• The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription

  2001cited by this paper
• The Histone Acetyltransferase, hGCN5, Interacts with and Acetylates the HIV Transactivator, Tat*

  2001cited by this paper
• Acetylation of Histones and Transcription-Related Factors

  2000cited by this paper
• Structure and function of a human TAFII250 double bromodomain module.

  2000cited by this paper
• The Human Factors YY1 and LSF Repress the Human Immunodeficiency Virus Type 1 Long Terminal Repeat via Recruitment of Histone Deacetylase 1

  2000cited by this paper
• Acetylation of the HIV-1 Tat protein by p300 is important for its transcriptional activity.

  1999cited by this paper
• HIV‐1 Tat transcriptional activity is regulated by acetylation

  1999influential reference
• Structure and ligand of a histone acetyltransferase bromodomain

  1999cited by this paper
• HIV-1 tat binds TAFII250 and represses TAFII250-dependent transcription of major histocompatibility class I genes.

  1998cited by this paper
• HIV-1 tat transactivator recruits p300 and CREB-binding protein histone acetyltransferases to the viral promoter.

  1998cited by this paper
• Transcriptional activation and chromatin remodeling of the HIV‐1 promoter in response to histone acetylation.

  1996cited by this paper
• LYSP100-associated nuclear domains (LANDs): description of a new class of subnuclear structures and their relationship to PML nuclear bodies.

  1996cited by this paper
• Identification and Characterization of a Leukocyte-specific Component of the Nuclear Body*

  1996cited by this paper
• Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation.

  1993cited by this paper
• brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2.

  1992cited by this paper

• Acetylation in Viral Infection and Disease.

  2025cites this paper
• Efficacy and Toxicity Analysis of Selective BET Bromodomain Inhibitors in Models of Inflammatory Liver Disease.

  2025cites this paper
• Successes and challenges in the development of BD1-selective BET inhibitors: a patent review

  2024cites this paper
• Bromodomain and Extra-Terminal Proteins in Brain Physiology and Pathology: BET-ing on Epigenetic Regulation

  2023cites this paper
• Latency Reversal and Clearance of Persistent HIV Infection.

  2022cites this paper
• Viral Hijacking of BET Proteins

  2022cites this paper
• Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections

  2022cites this paper
• Are BET Inhibitors yet Promising Latency-Reversing Agents for HIV-1 Reactivation in AIDS Therapy?

  2021cites this paper
• Chemogenomics for drug discovery: clinical molecules from open access chemical probes

  2021cites this paper
• Pharmacological Activation of Non-canonical NF-κB Signaling Activates Latent HIV-1 Reservoirs In Vivo

  2020cites this paper
• Inhibitors of bromodomain and extra‐terminal proteins for treating multiple human diseases

  2020cites this paper
• A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

  2020cites this paper
• Genetic and epigenetic regulation of natural resistance to HIV-1 infection: new approaches to unveil the HESN secret

  2020cites this paper
• Curing HIV: Seeking to Target and Clear Persistent Infection.

  2020cites this paper
• Bromodomain and BET family proteins as epigenetic targets in cancer therapy: their degradation, present drugs, and possible PROTACs

  2020cites this paper
• Novel phenanthridin-6(5H)-one derivatives as potent and selective BET bromodomain inhibitors: Rational design, synthesis and biological evaluation.

  2019cites this paper
• HIV "shock and kill" therapy: In need of revision.

  2019cites this paper
• Post-translational Modification-Based Regulation of HIV Replication

  2018cites this paper
• The Short Isoform of BRD4 Promotes HIV-1 Latency by Engaging Repressive SWI/SNF Chromatin-Remodeling Complexes.

  2017cites this paper
• The identification of new ATAD2 bromodomain inhibitors: the application of combined ligand and structure-based virtual screening

  2017cites this paper
• Stochastic principles governing alternative splicing of RNA

  2017cites this paper
• Inhibitors of BRD4 Protein from a Marine-Derived Fungus Alternaria sp. NH-F6

  2017cites this paper
• Drug Discovery Targeting Bromodomain-Containing Protein 4

  2017cites this paper
• Predicting and Monitoring Responses to Epigenetic Drugs

  2016cites this paper
• Interaction of vectors and parental viruses with the host genome.

  2016cites this paper
• Therapeutics Targeting Protein Acetylation Perturb Latency of Human Viruses.

  2016cites this paper
• Open Access Target Validation Is a More Efficient Way to Accelerate Drug Discovery

  2015cites this paper
• Histone Recognition

  2015cites this paper
• Manipulation of the host protein acetylation network by human immunodeficiency virus type 1

  2015influential citation
• Discovery of Chemical Inhibitors of Human Bromodomains.

  2015cites this paper
• Activating Latent HIV by Inhibiting Bromodomain Proteins

  2015cites this paper
• How Might We Cure HIV?

  2014cites this paper
• Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review 11

  2014cites this paper
• Emerging strategies to deplete the HIV reservoir

  2014cites this paper
• INTERNATIONAL UNION OF BASIC AND CLINICAL PHARMACOLOGY REVIEW Epigenetic pathway targets for the treatment of disease: accelerating progress in the development of pharmacological tools: IUPHAR Review 11

  2014cites this paper
• HIV Eradication: Combinatorial Approaches to Activate Latent Viruses

  2014cites this paper
• The bromodomain: from epigenome reader to druggable target.

  2014influential citation