Acute liver injury following infection with a cytopathic strain of duck hepatitis B virus

A variant avian hepadnavirus that has been shown to destroy hepatocytes in vitro was found to be cytopathic in viva. A single amino acid change of gly cine to glutamic acid at position 133 (G133E) in the preS protein of duck h epatitis B virus (DHBV) caused an increase in the intranuclear pool of vira l covalently closed circular DNA (cccDNA), resulting in a transient elevati on of viral replication and eventual hepatocyte destruction. In vivo viral infection with the G133E virus was compared with infection with wild-type v irus over a 72-day period. Birds were inoculated with virus at day 2 post-h atch to ensure a high percentage of infected hepatocytes and potential pers istence of virus. Birds infected with the G133E virus had increased peripor tal cellular proliferation and numerous lysed apoptotic hepatocytes followi ng 100% infection of hepatocytes. The liver damage within G133E virus-infec ted birds subsided over time, resulting in mild chronic hepatitis that was similar to that observed within wild-type virus-infected birds. The subside nce of liver damage in G133E virus-infected birds coincided with a reductio n of viral cccDNA to wild-type virus levels in the liver. Our study indicat es that maintenance of wild-type levels of viral cccDNA promotes persistenc e of virus infection by establishing a noncytopathic infection.