ArticlePLoS pathogens2013
Brd4 is displaced from HPV replication factories as they expand and amplify viral DNA.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
- BRD4: From molecular understanding to therapeutics development.Molecular cell · 2026Review
- Eyes Toward the Clinic: Selective Inhibition and Degradation Approaches to Bromodomain-Containing Proteins.Chembiochem : a European journal of chemical biology · 2026Review
- Topoisomerase IIα orchestrates secretion of IL-6 and IL-8 with human papillomavirus replication.Virologica Sinica · 2025Article
- Association of hepatitis B virus genomes with active chromatin hubs challenges host replication fidelity, leading to DNA damage.Journal of virology · 2025Article
- Activation of the HPV16 late promoter by viral E2 and cellular BRD4 and ZC3H4 proteins.Journal of virology · 2025Article
- Chromatin assembly by the histone chaperone HIRA facilitates Human Papillomavirus replication.bioRxiv : the preprint server for biology · 2025Article
- BRD4 as a potential target for human papillomaviruses associated cancer.Journal of medical virology · 2023Review
- Review
- The DNA Damage Sensor MRE11 Regulates Efficient Replication of the Autonomous Parvovirus Minute Virus of Mice.Journal of virology · 2023Article
- Effects of Caffeine, a DNA Damage Response Inhibitor, on Papillomavirus Genome Replication.Pathogens (Basel, Switzerland) · 2022Article
- Viral Hijacking of BET Proteins.Viruses · 2022Review
- Article
- Relevance of BET Family Proteins in SARS-CoV-2 Infection.Biomolecules · 2021Review
- BRD4S interacts with viral E2 protein to limit human papillomavirus late transcription.Journal of virology · 2021Article
- Persistent Human Papillomavirus Infection.Viruses · 2021Review
- Article
- Multiple Roles of Brd4 in the Infectious Cycle of Human Papillomaviruses.Frontiers in molecular biosciences · 2021Review
- Article
- Uncovering the Role of the E1 Protein in Different Stages of Human Papillomavirus 18 Genome Replication.Journal of virology · 2020Article
- Phosphorylation of the Human Papillomavirus E2 Protein at Tyrosine 138 Regulates Episomal Replication.Journal of virology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Replication foci are generated by many viruses to concentrate and localize viral DNA synthesis to specific regions of the cell. Expression of the HPV16 E1 and E2 replication proteins in keratinocytes results in nuclear foci that recruit proteins associated with the host DNA damage response. We show that the Brd4 protein localizes to these foci and is essential for their formation. However, when E1 and E2 begin amplifying viral DNA, Brd4 is displaced from the foci and cellular factors associated with DNA synthesis and homologous recombination are recruited. Differentiated HPV-infected keratinocytes form similar nuclear foci that contain amplifying viral DNA. We compare the different foci and show that, while they have many characteristics in common, there is a switch between early Brd4-dependent foci and mature Brd4-independent replication foci. However, HPV genomes encoding mutated E2 proteins that are unable to bind Brd4 can replicate and amplify the viral genome. We propose that, while E1, E2 and Brd4 might bind host chromatin at early stages of infection, there is a temporal and functional switch at later stages and increased E1 and E2 levels promote viral DNA amplification, displacement of Brd4 and growth of a replication factory. The concomitant DNA damage response recruits proteins required for DNA synthesis and repair, which could then be utilized for viral DNA replication. Hence, while Brd4 can enhance replication by concentrating viral processes in specific regions of the host nucleus, this interaction is not absolutely essential for HPV replication.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.