Hepatitis B virus covalently closed circular DNA (cccDNA)

Hepatitis B virus covalently closed circular DNA (cccDNA) is a unique, episomal form of the viral genome that plays a central role in the life cycle and persistence of hepatitis B virus (HBV). It serves as the transcriptional template for all HBV RNAs and is essential for viral replication and chronic infection. It exists as a double-stranded, covalently closed circular DNA molecule that forms a minichromosome within the nucleus of infected hepatocytes. Its stability underlies chronic HBV infection, and it can persist in liver cells even after apparent clinical cure or antiviral treatment—posing a major barrier to eradication efforts. Residual cccDNA may reactivate if immune control wanes or immunosuppression occurs.

Current antiviral therapies suppress HBV replication but do not eliminate nuclear cccDNA. Research focuses on understanding its formation/maintenance mechanisms to develop targeted therapies against it.