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

Control of cccDNA function in hepatitis B virus infection☆

  • Massimo Levrero

      Affiliations

    • Department of Internal Medicine, Sapienza University of Rome, Policlinico Umberto I, Viale del Policlinico 155, 0061 Rome, Italy
    • Oncogenomic Center, Andrea Cesalpino Foundation, Laboratory of Gene Expression, Regina Elena Cancer Institute, Rome, Italy
    • Laboratory of Gene Expression, Cenci Bolognetti Foundation, Sapienza University of Rome, Rome, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39 06 52662601, +39 06 49970892; fax: +39 06 49383333.
    • ,
  • Teresa Pollicino

      Affiliations

    • Department of Internal Medicine, Unit of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
    • ,
  • Jorg Petersen

      Affiliations

    • Liver Centre Hamburg, IFI Institute for Interdisciplinary Medicine at Asclepius Klinik S. Georg, Hamburg, Germany
    • ,
  • Laura Belloni

      Affiliations

    • Department of Gene Expression, Sapienza University of Rome, Rome, Italy
    • ,
  • Giovanni Raimondo

      Affiliations

    • Department of Internal Medicine, Unit of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy
    • ,
  • Maura Dandri

      Affiliations

    • Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

published online 10 June 2009.

Associate Editor: F. Zoulim

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

 

☆ 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.

PII: S0168-8278(09)00389-4

doi:10.1016/j.jhep.2009.05.022

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

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