The objectives of the proposed research are to understand in detail the process by which hepadna viruses infect liver cells and replicate to produce progeny virus. We will use this information to design new strategies for antiviral therapy, and to test such strategies on infected hepatocytes in culture and in animal models. Interruption of the carrier state for hepadna-virus production will greatly reduce the risk for hepatocellular carcinoma in both the primary host and in potential secondary hosts (e.g. children of HBV carrier mothers). We will employ the duck hepatitis B virus model of HBV for these studies, since virus infection can be examined in both cultures of primary hepatocytes and in ducks. We will define and characterize the viral and cellular receptors for virus attachment and uptake. We will examine the functions and behavior of viral gene products in the replicative cycle by controlled expression of their genes in primary hepatocytes. Finally, we will attempt to develop methods for introducing and expressing genes that interfere with virus production in persistently infected cells and animals.
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