Background & Aims: HBV persists in the nucleus of infected hepatocytes as a covalently closed circular DNA (cccDNA) episome that constitutes the template for viral RNA and protein synthesis. Both HBx and HBc (core) viral proteins associate with cccDNA but, while HBx is required for viral transcription, the role of HBc is still unclear. The aim of this study was to determine if HBc derived from incoming nucleocapsid can associate with cccDNA before the onset of viral transcription and protein production.
Methods: Chromatin immunoprecipitation assays were performed in native conditions. In addition, differentiated HepaRG (dHepaRG) cells infected with HBx-deficient HBV were used to investigate if HBc delivered by incoming virions can associate with cccDNA.
Results: Our results indicate that HBc can associate with cccDNA in the absence of viral transcription and protein synthesis. In dHepaRG cells, this association is stable for at least 6 weeks.
Conclusion: These results suggest that virion-delivered HBc may participate at an early stage of cccDNA formation and/or transcription.
Lay Summary: The hepatitis B virus genome is released into the nucleoplasm of infected cells after disassembly of the viral nucleocapsids at the nuclear membrane. Herein, we show for the first time that virion-delivered hepatitis B core protein, a component of the viral capsid, can stably associate with integrated viral DNA.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363821 | PMC |
| http://dx.doi.org/10.1016/j.jhepr.2021.100330 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters.
Clin Mol Hepatol
December 2024
Department of Medicine, Queen Mary Hospital, The University of Hong Kong.
Background: Plasma pregenomic hepatitis B virus RNA (pgRNA) is a novel biomarker in chronic hepatitis B infection (CHB). We aimed to describe the longitudinal profile of pgRNA and factors influencing its levels in CHB patients on nucleoside analogue (NUC).
Methods: Serial plasma samples from 1354 CHB patients started on first-line NUC were evaluated.
HBV serum RNA kinetics during nucleic acid polymers based therapy predict functional cure.
Antiviral Res
December 2024
Program for Experimental & Theoretical Modeling, Division of Hepatology, Department of Medicine, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA. Electronic address:
Serum HBV-RNA (seRNA) was proposed to be a circulating marker of cccDNA transcriptional activity in hepatocytes. The combination of tenofovir-disoproxil-fumarate (TDF) and pegylated-interferon-alpha-2a (pegIFN) with nucleic-acid polymer (NAP) treatment was associated with a relatively high rate of functional cure (FC) 48 weeks after discontinuation of all therapy. We aim to characterize seRNA kinetics under TDF and pegIFN±NAP combination therapies.
View Article and Find Full Text PDFRNA Helicase DDX5 in Association With IFI16 and the Polycomb Repressive Complex 2 Silences Transcription of the Hepatitis B Virus by Interferon.
J Med Virol
December 2024
Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana, USA.
RNA helicase DDX5 is a host restriction factor for hepatitis B virus (HBV) biosynthesis. Mass spectrometry (LC-MS/MS) identified significant DDX5-interacting partners, including interferon-inducible protein 16 (IFI16) and RBBP4/7, an auxiliary subunit of polycomb repressive complex 2 (PRC2). DDX5 co-eluted with IFI16, RBBP4/7, and core PRC2 subunits in size exclusion chromatography fractions derived from native nuclear extracts.
View Article and Find Full Text PDFAugmented epigenetic repression of hepatitis B virus covalently closed circular DNA by interferon-α and small-interfering RNA synergy.
mBio
December 2024
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Research Unit of Cure of Chronic Hepatitis B Virus Infection (CAMS), Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, School of Basic Medical Sciences, Shanghai Medical College Fudan University, Shanghai, China.
Unlabelled: The persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key obstacle for HBV cure. This study aims to comprehensively assess the effect of interferon (IFN) and small-interfering RNA (siRNA) combination on the cccDNA minichromosome. Utilizing both cell and mouse cccDNA models, we compared the inhibitory effects of IFNα, siRNA, and their combination on cccDNA activity and assessed its epigenetic state.
View Article and Find Full Text PDFHBV Antigen-Guided Switching Strategy From Nucleos(t)ide Analogue to Interferon: Avoid Virologic Breakthrough and Improve Functional Cure.
J Med Virol
November 2024
Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Article Synopsis
- A study involving 80 patients with chronic hepatitis B (CHB) found that 15% experienced virologic breakthrough (VBT) after switching from nucleos(t)ide analogue (NA) therapy to pegylated interferon alpha (Peg-IFN-α) treatment.
- Patients who had higher levels of HBcrAg (≥5 logU/mL) and HBsAg (≥100 IU/mL) showed a significantly increased risk of VBT and were less likely to achieve HBsAg clearance post-therapy.
- The research indicates that monitoring HBcrAg and HBsAg levels can provide insights into immune responses and help prevent VBT, potentially improving the chances of achieving a functional cure for CH
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!