Other Hepadnaviridae (Avihepadnaviridae (DHBV) and Orthohepadnaviridae (WHV))
Stephen A. Locarnini
Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia
Search for more papers by this authorMichael Roggendorf
Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Search for more papers by this authorStephen A. Locarnini
Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia
Search for more papers by this authorMichael Roggendorf
Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
Search for more papers by this authorHoward C. Thomas BSc, PhD, FRCP, FRCPath, FMedSci
Emeritus Professor of Hepatology, Department of Medicine, Imperial College London, London, UK
Search for more papers by this authorAnna S.F. Lok MD
Alice Lohrman Andrews Research Professor in Hepatology, Director of Clinical Hepatology, Professor of Internal Medicine, Associate Chair for Clinical Research, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA
Search for more papers by this authorStephen A. Locarnini MBBS, BSc(Hons), PhD, FRCPath
Head, Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, VIC, Australia
Search for more papers by this authorArie J. Zuckerman MD, DSc, FRCP, FRCPath, FMedSci
Emeritus Professor of Medical Microbiology, Formerly Principal and Dean, Royal Free Hospital School of Medicine
Search for more papers by this authorSummary
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 identified 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 finches 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.
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