DUCK HEPATITIS B VIRUS: INFECTION AND DISEASE

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We propose to continue our studies of duck hepatitis B virus (DHBV) infection of domestic ducks as an animal model of hepatitis B virus, which is associated with hepatitis, hepatomas, and immune complex disease in man. DHBV is present in 5-10% of the Peking ducks of many domestic flocks in the U.S. We plan to investigate the long-term course of DHBV-infection and document the associated disease. Hepatomas have been observed in areas of China where DHBV is endemic. We will study duck hepatomas from China and any that might appear in our flock for the presence of DHBV. Tumors will be analyzed for viral DNA by Southern blotting and integrated viral DNA will be cloned for further characterization. We will continue our analysis of DHBV surface and core antigen polypeptides, and will produce monoclonal as well as polyvalent antibodies to them to provide sensitive serological tests. We will study the appearance and relationship of different viral DNA forms during the course of infection in embryonated eggs, and attempt to grow virus in culture of duck embryo cells. Finally we will study the host range of DHBV by injection of the virus into different varieties of ducks, other species of fowl, and non-avian species. This virus-host system may offer certain advantages over other hepadna virus-host systems. Among these is the ease with which ducks and embryonated duck eggs can be obtained and experimentally manipulated, the ease with which embryos can be infected, the ease with which embryonic tissues can be cultured in vitro, the apparent difference in disease manifestations in different hosts (acute hepatitis in Khaki Campbell and not in Peking ducklings) and the possible association of the virus and hepatomas in ducks in China. These advantages justify the further development of the duck virus system in order to understand the mechanism of virus replication and the pathogenesis of diseases associated with infection.