Virologica Sinica

, Volume 32, Issue 6, pp 454–464 | Cite as

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

  • Mengying Ji
  • Kanghong HuEmail author


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.


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



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.

Compliance with Ethics Guidelines

The authors declare that they have no conflicts of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Sino-German Biomedical Center, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Provincial Cooperative Innovation Center of Industrial Fermentation, National “111” Center for Cellular Regulation and Molecular PharmaceuticsHubei University of TechnologyWuhanChina

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