show Abstracthide AbstractThe Eastern woodchuck Marmota monax, native to the mid-Atlantic states of North America, is naturally infected with woodchuck hepatitis virus (WHV), a hepadnavirus that is closely related to the human hepatitis B virus (HBV). Neo-natal infection of woodchucks with WHV, parallels the main route of human (vertical) transmission for chronic HBV infection and displays a disease course similar to that in HBV-infected patients. The animal model has been extensively used over the past three decades to study the pathogenesis of chronic HBV infection and in the preclinical evaluation of efficacy, and more importantly, safety of antiviral compounds for the prevention of HBV disease sequelae, including chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC). In this study, we present a high-quality genome sequence and the annotation of the Eastern woodchuck and a comparison of the woodchuck genome with both humans and mice. The overall data provided will be valuable for the continued development of the woodchuck as an animal model for treatment of CHB and HCC from which the current over 350 million chronic carriers of HBV worldwide could greatly benefit.