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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
Mechanisms of Hepatitis B Virus cccDNA and Minichromosome Formation and HBV Gene Transcription
Andoni Gómez-Moreno1, Alexander Ploss1
1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Insights
Hepatitis B virus (HBV) persistence relies on covalently closed circular DNA (cccDNA) formation. This review explores cccDNA minichromosome assembly and HBV gene transcription regulation, identifying research gaps.
Area of Science:
- Virology
- Molecular Biology
- Hepatology
Background:
- Hepatitis B virus (HBV) causes chronic hepatitis B, risking fibrosis, cirrhosis, and liver cancer in over 300 million people.
- HBV, a Hepadnaviridae family virus, has a complex replication cycle, with key aspects remaining unclear.
- Covalently closed circular DNA (cccDNA) is crucial for HBV persistence, serving as the primary template for viral gene transcription.
Purpose of the Study:
- To review the formation of HBV cccDNA and its associated viral minichromosome.
- To examine the regulation of HBV gene transcription from the cccDNA template.
- To identify and highlight unresolved questions in HBV cccDNA biology and transcription.
Main Methods:
- Literature review of HBV replication and cccDNA formation.
- Analysis of studies on HBV minichromosome structure and function.
- Synthesis of research on transcriptional regulation of HBV genes.
Main Results:
- cccDNA is formed from relaxed circular DNA (rcDNA) and persists as a chromatinized minichromosome.
- This minichromosome is the central hub for HBV gene expression.
- Mechanisms of cccDNA formation and transcription regulation are complex and not fully elucidated.
Conclusions:
- Understanding cccDNA formation and transcriptional control is vital for combating chronic HBV infection.
- Further research is needed to address knowledge gaps in HBV persistence and gene regulation.
- Targeting cccDNA and its transcription could offer new therapeutic strategies for hepatitis B.
Abstract:
Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus of the Hepadnaviridae family. While HBV was discovered more than 50 years ago, many aspects of its replicative cycle remain incompletely understood. Central to HBV persistence is the formation of covalently closed circular DNA (cccDNA) from the incoming relaxed circular DNA (rcDNA) genome. cccDNA persists as a chromatinized minichromosome and is the major template for HBV gene transcription. Here, we review how cccDNA and the viral minichromosome are formed and how viral gene transcription is regulated and highlight open questions in this area of research.
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