ArticlePLoS pathogens2018
Flap endonuclease 1 is involved in cccDNA formation in the hepatitis B virus.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 109 citations in OpenAlex.
- Orthogonal CRISPR screens and human liver chimeric mice identify hepatitis B virus host factors.bioRxiv : the preprint server for biology · 2026Article
- Review
- DOCK11 promotes HBV cccDNA formation through a PARP1-dependent mechanism.Microbiology spectrum · 2026Article
- Nucleotide excision repair and poly(ADP-ribose) polymerase 1 cooperate in HBV cccDNA synthesis: A potential viral therapeutic target.JHEP reports : innovation in hepatology · 2026Article
- Lead Optimization of Xanthone Derivatives as Hepatitis B Virus cccDNA Reducers: Design, Synthesis, and Bioevaluation.ACS medicinal chemistry letters · 2026Article
- Insight into the Biology of Hepatitis B Virus and Recent Therapeutic Approaches.Current microbiology · 2026Review
- Identification of glycogen synthase kinase 3alpha/beta as a host factor required for HBV transcription using high-throughput screening.Hepatology (Baltimore, Md.) · 2025Article
- Association of hepatitis B virus genomes with active chromatin hubs challenges host replication fidelity, leading to DNA damage.Journal of virology · 2025Article
- Translesion DNA polymerases Rev1 and PolH promote LTR-retrotransposon transcription by safeguarding Pol II occupancy in both germline and somatic tissues of Drosophila.Nucleic acids research · 2025Article
- Genome integration of human DNA oncoviruses.Journal of virology · 2025Review
- Syndecan 2 proteoglycan serves as a hepatitis B virus cell attachment receptor.Journal of virology · 2025Article
- NEDD4-binding protein 1 suppresses hepatitis B virus replication by regulating viral RNAs.The Journal of general virology · 2025Article
- Host 3' flap endonuclease Mus81 plays a critical role in trimming the terminal redundancy of hepatitis B virus relaxed circular DNA during covalently closed circular DNA formation.PLoS pathogens · 2025Article
- Hepatitis B core-related antigen as a promising serological marker for monitoring hepatitis B virus cure.World journal of hepatology · 2025Review
- From the Cytoplasm into the Nucleus-Hepatitis B Virus Travel and Genome Repair.Microorganisms · 2025Review
- Hepatitis B virus hijacks MRE11-RAD50-NBS1 complex to form its minichromosome.PLoS pathogens · 2025Article
- Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA.Genes & diseases · 2025Review
- Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.Pathogens (Basel, Switzerland) · 2024Review
- Meeting report of the 37th International Conference on Antiviral Research in Gold Coast, Australia, May 20-24, 2024, organized by the International Society for Antiviral Research.Antiviral research · 2024Article
- Exosomes for CRISPR-Cas9 Delivery: The Cutting Edge in Genome Editing.Molecular biotechnology · 2024Review
10 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV) is one of the major etiological pathogens for liver cirrhosis and hepatocellular carcinoma. Chronic HBV infection is a key factor in these severe liver diseases. During infection, HBV forms a nuclear viral episome in the form of covalently closed circular DNA (cccDNA). Current therapies are not able to efficiently eliminate cccDNA from infected hepatocytes. cccDNA is a master template for viral replication that is formed by the conversion of its precursor, relaxed circular DNA (rcDNA). However, the host factors critical for cccDNA formation remain to be determined. Here, we assessed whether one potential host factor, flap structure-specific endonuclease 1 (FEN1), is involved in cleavage of the flap-like structure in rcDNA. In a cell culture HBV model (Hep38.7-Tet), expression and activity of FEN1 were reduced by siRNA, shRNA, CRISPR/Cas9-mediated genome editing, and a FEN1 inhibitor. These reductions in FEN1 expression and activity did not affect nucleocapsid DNA (NC-DNA) production, but did reduce cccDNA levels in Hep38.7-Tet cells. Exogenous overexpression of wild-type FEN1 rescued the reduced cccDNA production in FEN1-depleted Hep38.7-Tet cells. Anti-FEN1 immunoprecipitation revealed the binding of FEN1 to HBV DNA. An in vitro FEN activity assay demonstrated cleavage of 5'-flap from a synthesized HBV DNA substrate. Furthermore, cccDNA was generated in vitro when purified rcDNA was incubated with recombinant FEN1, DNA polymerase, and DNA ligase. Importantly, FEN1 was required for the in vitro cccDNA formation assay. These results demonstrate that FEN1 is involved in HBV cccDNA formation in cell culture system, and that FEN1, DNA polymerase, and ligase activities are sufficient to convert rcDNA into cccDNA in vitro.
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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.