Other Hepadnaviridae (Avihepadnaviridae (DHBV) and Orthohepadnaviridae (WHV))

All members of the family Hepadnaviridae are primarily hepatotropic viruses that contain double-stranded DNA genomes that are replicated via reverse transcription of a pregenomic RNA template. There are two subgroups within this family: mammalian and avian. The avian members include duck hepatitis B virus (DHBV), heron hepatitis B virus, Ross goose hepatitis B virus, stork hepatitis B virus, and the recently identifi ed parrot hepatitis B virus. The DHBV model was essential in determining the novel and complex replication strategy of Hepadnaviruses and was a very useful model in the assessment and development of potential direct-acting antiviral agents. The detection of endogenous avian hepadnavirus DNA integrated into the genomes of zebra fi nches has revealed the deep evolutionary origin of Hepadnaviruses. The animal nonhuman primate members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), ground squirrel hepatitis virus, and arctic squirrel virus. The WHV and its host, the eastern woodchuck (Marmota marmot), have also comprised a very valuable model system for studying hepatitis B virus infection in humans. Its mode of replication and its pathogenesis resemble very much acute and chronic hepatitis B infection. Since the establishment of immunological tools to characterize the immune response in this model, woodchucks can now be used to test new antiviral drugs and also develop new vaccines, especially immunomodulatory approaches to treat chronic hepadnaviral infections. Combining antiviral treatment with nucleos(t)ide analogs and therapeutic vaccines, including prime boost regimens, has been shown to induce a potent T cell response in chronic WHV carrier woodchucks. This combination therapy seems to be a promising approach for the treatment of chronic hepatitis B to suppress viral replication and even eliminate HBV in the human host.