ArticleThe Journal of biological chemistry
Identification and characterization of a G-quadruplex structure in the pre-core promoter region of hepatitis B virus covalently closed circular DNA.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 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
- hnRNPA2B1 induces HBV cccDNA degradation by recruiting APOBEC3B.Nucleic acids research · 2026Article
- Review
- Review
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- G-quadruplex folding in Xist RNA antagonizes PRC2 activity for stepwise regulation of X chromosome inactivation.Molecular cell · 2024Article
- Review
- G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes.Nucleic acids research · 2024Article
- G-Quadruplexes in the Regulation of Viral Gene Expressions and Their Impacts on Controlling Infection.Pathogens (Basel, Switzerland) · 2024Review
- G-Quadruplexes in the Viral Genome: Unlocking Targets for Therapeutic Interventions and Antiviral Strategies.Viruses · 2023Review
- Unfolding of an RNA G-quadruplex motif in the negative strand genome of porcine reproductive and respiratory syndrome virus by host and viral helicases to promote viral replication.Nucleic acids research · 2023Article
- G-quadruplexes in the evolution of hepatitis B virus.Nucleic acids research · 2023Article
- Targeting G-quadruplexes to achieve antiviral activity.Bioorganic & medicinal chemistry letters · 2023Review
- Development and evaluation of a semi-nested PCR technique for amplification and determination of different surface gene variation patterns in patients with chronic HBV infection: development of an amplification method for HBV S gene.Gastroenterology and hepatology from bed to bench · 2023Article
- G4-quadruplex-binding proteins: review and insights into selectivity.Biophysical reviews · 2022Review
- Review
- The emerging role of DEAD/H-box helicases in hepatitis B virus infection.Frontiers in cellular and infection microbiology · 2022Review
- Can G-quadruplex become a promising target in HBV therapy?Frontiers in immunology · 2022Review
- G-Quadruplexes in Neurobiology and Virology: Functional Roles and Potential Therapeutic Approaches.JACS Au · 2021Review
- Molecular mechanism of quorum sensing inhibition in Streptococcus by the phage protein paratox.The Journal of biological chemistry · 2021Article
Corrections and comments
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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
Approximately 250 million people worldwide are chronically infected with the hepatitis B virus (HBV) and are at increased risk of developing cirrhosis and hepatocellular carcinoma. The HBV genome persists as covalently closed circular DNA (cccDNA), which serves as the template for all HBV mRNA transcripts. Current nucleos(t)ide analogs used to treat HBV do not directly target the HBV cccDNA genome and thus cannot eradicate HBV infection. Here, we report the discovery of a unique G-quadruplex structure in the pre-core promoter region of the HBV genome that is conserved among nearly all genotypes. This region is central to critical steps in the viral life cycle, including the generation of pregenomic RNA, synthesis of core and polymerase proteins, and genome encapsidation; thus, an increased understanding of the HBV pre-core region may lead to the identification of novel anti-HBV cccDNA targets. We utilized biophysical methods (circular dichroism and small-angle X-ray scattering) to characterize the HBV G-quadruplex and the effect of three distinct G to A mutants. We also used microscale thermophoresis to quantify the binding affinity of G-quadruplex and its mutants with a known quadruplex-binding protein (DHX36). To investigate the physiological relevance of HBV G-quadruplex, we employed assays using DHX36 to pull-down cccDNA and compared HBV infection in HepG2 cells transfected with wild-type and mutant HBV plasmids by monitoring the levels of genomic DNA, pregenomic RNA, and antigens. Further evaluation of this critical host-protein interaction site in the HBV cccDNA genome may facilitate the development of novel anti-HBV therapeutics against the resilient cccDNA template.
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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.