1. Volume 42, Issue 3, Pages 302-308 (March 2005)
New insight on hepatitis B virus persistence from the study of intrahepatic viral cccDNA 
Fabien Zoulim 
Journal of Hepatology 
Volume 42, Issue 3, Pages (March 2005)
DOI: /j.jhep
Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

2. Fig. 1
The HBV replication cycle and the viral DNA replicative intermediates. The left panel shows all the major steps required in the viral replication cycle. Nucleoside(tide) analogs mainly inhibit the viral minus strand DNA synthesis (reverse transcription), and plus strand DNA synthesis (DNA dependent DNA polymerase activity) within viral nucleocapsids. These drugs do not directly affect viral cccDNA which is maintained in the nucleus of infected cells, therefore requiring long-term treatment for a sustained control of viral replication. The right panel shows the analysis of intracellular viral DNA by southern blot hybridization after agarose gel electrophoresis. RC: relaxed circular DNA; DSL: double stranded linear DNA; SS: single stranded DNA; ccc: covalently closed circular DNA.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

3. Fig. 2
Formation of the recalcitrant cccDNA, a difficult target for antiviral therapy Formation of cccDNA from incoming virions implies the trafficking of nucleocapsids to the nucleus, the entry of relaxed circular DNA in the nucleus, the completion of plus strand DNA synthesis, the removal of the polymerase primer for minus strand DNA synthesis and of the RNA primer for plus strand DNA synthesis, the ligation of both DNA strand extremities, and its incorporation in the nucleosome to form a non-integrated mini-chromosome. Currently, none of the viral polymerase inhibitors has been able to prevent de novo cccDNA formation.
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

4. Fig. 3
Detection of cccDNA by PCR. The figure shows the structure of RC and ccc DNA and the location of the primers to preferentially amplify cccDNA versus RC DNA (from Ref. [34]).
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

5. Fig. 4
Decline of cccDNA and HBsAg in patients undergoing adefovir dipivoxil therapy. Serum viral load, total intrahepatic DNA, and intrahepatic cccDNA declined during a 48 week period administration of adefovir dipivoxil. Serum HBsAg also declined significantly during antiviral therapy. Viral load declined with the following order: Serum viral load>total intrahepatic DNA>intrahepatic cccDNA (from Ref. [34]).
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2004 European Association for the Study of the Liver Terms and Conditions

6. Fig. 5
Parallel decline of serum HBsAg and intrahepatic cccDNA during adefovir dipivoxil therapy. Quantification of serum HBsAg and intrahepatic cccDNA showed a significant correlation between the changes observed in both markers during antiviral therapy, suggesting that quantification of serum HBsAg may represent an interesting non-invasive surrogate marker of cccDNA (from Ref. [34]).
Journal of Hepatology  , DOI: ( /j.jhep )
Copyright © 2004 European Association for the Study of the Liver Terms and Conditions