cccDNA (covalently closed circular DNA) is a special DNA structure that arises during the propagation of some viruses in the cell nucleus and may remain permanently there. It is a double-stranded DNA that originates in a linear form that is ligated by means of DNA ligase to a covalently closed ring. In most cases, transcription of viral DNA can occur from the circular form only. The cccDNA of viruses is also known as episomal DNA or occasionally as a minichromosome.
The existence of a cccDNA during the propagation does not differentiate taxonomic group of "real" retroviruses (Orthoretrovirinae) from the pararetrovirus.
cccDNA was first described in bacteriophages, but it was also found in some cell cultures where an infection of DNA viruses (Polyomaviridae) was detected. cccDNA is typical of Caulimoviridae and Hepadnaviridae, including the hepatitis B virus (HBV). cccDNA in HBV is formed by conversion of capsid-associated relaxed circular DNA (rcDNA). Following hepatitis B infections, cccDNA can remain following clinical treatment in liver cells and can rarely reactivate. The relative quantity of cccDNA present is an indicator for HBV treatment.