Control of cccDNA function in hepatitis B virus infection.
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.
Levrero
Massimo
M
Department of Internal Medicine, Sapienza University of Rome, Policlinico Umberto I, 0061 Rome, Italy. massimo.levrero@uniroma1.it
Pollicino
Teresa
T
Petersen
Jorg
J
Belloni
Laura
L
Raimondo
Giovanni
G
Dandri
Maura
M
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D004270:DNA, Circular / Q000187:drug effects / Q000502:physiology*; D004279:DNA, Viral / Q000187:drug effects / Q000502:physiology*; D044127:Epigenesis, Genetic; D006509:Hepatitis B / Q000188:drug therapy / Q000503:physiopathology* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D014779:Virus Replication / Q000502:physiology
D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral