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Updated: Oct 9, 2025

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
Research progress in hepatitis B virus covalently closed circular DNA
Xiaodong Zhang1, Yufei Wang2, Guang Yang1
1Department of Gastrointestinal Cancer Biology, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Insights
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) drives viral replication and liver cancer. This review details HBV cccDNA mechanisms, epigenetic modulation, and novel therapeutic strategies for its elimination.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Hepatitis B virus (HBV) infection is a major global health concern.
- HBV covalently closed circular DNA (cccDNA) is essential for viral replication and a persistent obstacle to cure.
- Epigenetic modulation of HBV cccDNA by host factors is linked to hepatocellular carcinoma (HCC) development.
Purpose of the Study:
- To review recent advances in understanding HBV cccDNA.
- To discuss factors influencing HBV cccDNA epigenetic modulation.
- To explore therapeutic strategies targeting HBV cccDNA.
Main Methods:
- Literature review of HBV cccDNA research.
- Analysis of host factors and epigenetic mechanisms.
- Discussion of serological biomarkers and drug effects.
Main Results:
- HBV X protein (HBx) modulates host epigenetic factors, linking cccDNA to hepatocarcinogenesis.
- Measurable serological biomarkers indicate cccDNA transcription.
- Current anti-HBV drugs have limited effects on cccDNA.
Conclusions:
- HBV cccDNA remains a significant challenge in HBV infection and HCC.
- Understanding cccDNA epigenetic modulation is crucial for developing effective therapies.
- Targeting HBV cccDNA offers a promising strategy for HBV cure and liver disease management.
Abstract:
Hepatitis B virus (HBV) infections are a global public health issue. HBV covalently closed circular DNA (cccDNA), the template for the transcription of viral RNAs, is a key factor in the HBV replication cycle. Notably, many host factors involved in HBV cccDNA epigenetic modulation promote the development of hepatocellular carcinoma (HCC). The HBV cccDNA minichromosome is a clinical obstacle that cannot be efficiently eliminated. In this review, we provide an update on the advances in research on HBV cccDNA and further discuss factors affecting the modulation of HBV cccDNA. Hepatitis B virus X protein (HBx) contributes to HBV cccDNA transcription and the development of hepatocarcinogenesis through modulating host epigenetic regulatory factors, thus linking the cccDNA to hepatocarcinogenesis. The measurable serological biomarkers of continued transcription of cccDNA, the effects of anti-HBV drugs on cccDNA, and potential therapeutic strategies targeting cccDNA are discussed in detail. Thus, this review describes new insights into HBV cccDNA mechanisms and therapeutic strategies for cleaning cccDNA, which will benefit patients with liver diseases.
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