Elsevier

Journal of Hepatology

Volume 51, Issue 3, September 2009, Pages 581-592
Journal of Hepatology

Review
Control of cccDNA function in hepatitis B virus infection

https://doi.org/10.1016/j.jhep.2009.05.022Get rights and content
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open access

The template of hepatitis B virus (HBV) transcription, the covalently closed circular DNA (cccDNA), plays a key role in the life cycle of the virus and permits the persistence of infection. Novel molecular techniques have opened new possibilities to investigate the organization and the activity of the cccDNA minichromosome in vivo, and recent advances have started to shed light on the complexity of the mechanisms controlling cccDNA function. Nuclear cccDNA accumulates in hepatocyte nuclei as a stable minichromosome organized by histone and non-histone viral and cellular proteins. Identification of the molecular mechanisms regulating cccDNA stability and its transcriptional activity at the RNA, DNA and epigenetic levels in the course of chronic hepatitis B (CH-B) infection may reveal new potential therapeutic targets for anti-HBV drugs and hence assist in the design of strategies aimed at silencing and eventually depleting the cccDNA reservoir.

Keywords

Hepatitis B virus
Covalently closed circular DNA
Chronic hepatitis B infection
cccDNA function

Abbreviations

HBV
hepatitis B virus
CH-B
chronic hepatitis B
HCC
hepatocellular carcinoma
RC
relaxed circular
PF-RC DNA
protein free relaxed circular
cccDNA
covalently closed circular DNA
NHEJ
nonhomologous end joining
DLS
double-stranded linear (DSL)
pgRNA
pregenomic RNA
LS
viral large surface protein
ChIP
chromatin immuno-precipitation

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The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript.