ArticleNucleic acids research2024
G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes.
Article in Nucleic acids research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Regulatory roles of G-quadruplexes and G-quadruplex-binding proteins across the enhancer and promoter of the HBV genome.Virology journal · 2026Article
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A key role for the exoribonuclease XRN1 in regulating the hepatitis B viral transcriptome.iScience · 2026Article
- hnRNPA2B1 induces HBV cccDNA degradation by recruiting APOBEC3B.Nucleic acids research · 2026Article
- Higher Selective Targeting of Telomeric Multimeric G-quadruplex by Natural Product Berberine.Current medicinal chemistry · 2026Article
- Role of cccDNA in the Quest for HBV Cure- Implications for HIV-HBV Coinfection.Current HIV/AIDS reports · 2025Review
- Perspectives on NcRNAs in HBV/cccDNA-driven HCC progression.Cancer cell international · 2025Review
- Beyond Structure: Methylation Fine-Tunes Stability and Folding Kinetics of bcl2Mid G-Quadruplex.Angewandte Chemie (International ed. in English) · 2025Article
- Tandemly Repeated G-Quadruplex Structures in the Pseudorabies Virus Genome: Implications for Epiberberine-Based Antiviral Therapy.International journal of molecular sciences · 2025Article
- HBV cccDNA: The Molecular Reservoir of Hepatitis B Persistence and Challenges to Achieve Viral Eradication.Biomolecules · 2025Review
- Review
- Emerging roles of liquid-liquid phase separation in liver innate immunity.Cell communication and signaling : CCS · 2024Review
- Review
- Mechanisms of Hepatitis B Virus cccDNA and Minichromosome Formation and HBV Gene Transcription.Viruses · 2024Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Phase separation regulates fundamental processes in gene expression and is mediated by the local concentration of proteins and nucleic acids, as well as nucleic acid secondary structures such as G-quadruplexes (G4s). These structures play fundamental roles in both host gene expression and in viral replication due to their peculiar localisation in regulatory sequences. Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is an episomal minichromosome whose persistence is at the basis of chronic infection. Identifying the mechanisms controlling its transcriptional activity is indispensable to develop new therapeutic strategies against chronic hepatitis B. The aim of this study was to determine whether G4s are formed in cccDNA and regulate viral replication. Combining biochemistry and functional studies, we demonstrate that cccDNA indeed contains ten G4s structures. Furthermore, mutations disrupting two G4s located in the enhancer I HBV regulatory region altered cccDNA transcription and viral replication. Finally, we showed for the first time that cccDNA undergoes phase separation in a G4-dependent manner to promote its transcription in infected hepatocytes. Altogether, our data give new insight in the transcriptional regulation of the HBV minichromosome that might pave the way for the identification of novel targets to destabilize or silence cccDNA.
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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.