Covalently closed circular DNA (cccDNA) of hepatitis B virus aggregates in the nucleus of infected hepatocytes as the original replication template of HBV to form a pool of cccDNA with a long half-life that cannot be cleared by existing antiviral drugs, and is the key to persistent infection of host hepatocytes and relapse after tolerance and discontinuation of antiviral therapy. The role of cccDNA in persistent HBV infection is unquestionable, and a cure for chronic hepatitis B will have to overcome this challenge. Currently, limited by the limitations of in vivo and in vitro experimental models, the biological properties of cccDNA
The establishment of cellular infection systems and small animal models will hopefully answer these questions in the near future. The complete elimination of
The complete elimination of cccDNA may be difficult to achieve with only one strategy, and the combined understanding of the biochemical characteristics of cccDNA, the way the body’s immune system clears cccDNA during acute infection, and the manipulation of the editing DNA
The combination of knowledge of the biochemical characteristics of cccDNA, the way the body’s immune system clears cccDNA during acute infection, and new techniques for manipulating edited DNA may hold promise. Hopefully, one day, slow hepatitis B will be cured in the same way as slow hepatitis C.