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. 2017 Dec 21;32(6):454–464. doi: 10.1007/s12250-017-4009-4

Recent advances in the study of hepatitis B virus covalently closed circular DNA

Mengying Ji 1, Kanghong Hu 1,✉
PMCID: PMC6598884  PMID: 29280054

Abstract

Chronic hepatitis B infection is caused by hepatitis B virus (HBV) and a total cure is yet to be achieved. The viral covalently closed circular DNA (cccDNA) is the key to establish a persistent infection within hepatocytes. Current antiviral strategies have no effect on the pre-existing cccDNA reservoir. Therefore, the study of the molecular mechanism of cccDNA formation is becoming a major focus of HBV research. This review summarizes the current advances in cccDNA molecular biology and the latest studies on the elimination or inactivation of cccDNA, including three major areas: (1) epigenetic regulation of cccDNA by HBV X protein, (2) immune-mediated degradation, and (3) genome-editing nucleases. All these aspects provide clues on how to finally attain a cure for chronic hepatitis B infection.

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Keywords: hepatitis B virus (HBV), covalently closed circular DNA (cccDNA), HBx, immunemediated, genome-editing nucleases

Acknowledgments

This study was supported by the Key Project of Hubei Province Natural Science Foundation (2014CFA075), the National Natural Science Foundation of China (31400153) and the Applied Basic Research Program (2015060101010033), Wuhan, China.

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