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Review | Open Access

Research progress in hepatitis B virus covalently closed circular DNA

Xiaodong Zhang1 ( ), Yufei Wang2, Guang Yang1
Department 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
Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China
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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.

Keywords

therapyHepatitis B viruscccDNAHBxhepatocarcinogenesisepigenetic modulation

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Cancer Biology & Medicine
Volume 19 Issue 4,
April 2022
Pages 415-431
DOI: 10.20892/j.issn.2095-3941.2021.0454
Cite this article:
Zhang X, Wang Y, Yang G. Research progress in hepatitis B virus covalently closed circular DNA. Cancer Biology & Medicine, 2022, 19(4): 415-431. https://doi.org/10.20892/j.issn.2095-3941.2021.0454

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Received: 26 August 2021
Accepted: 16 November 2021
Published: 01 April 2022
©2022 Cancer Biology & Medicine.

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