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.
cccDNA was first described in bacteriophages, but it was also found in some cell cultures where an infection of DNA viruses (Polyomaviridae) was detected.[1][2] 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).[3] 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.[4]