WOODCHUCK VIRUS--MOLECULAR BIOLOGICAL STUDIES

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The woodchuck hepatitis virus (WHV) is taxonomically and serologically related to the hepatitis B virus (HBV). Infection with each of these viruses is associated with acute and chronic hepatitis and hepatic cell carcinoma in their respective hosts and these associations appear to be etiological in nature. Thus, WHV infection of woodchucks provides a relevant and convenient model for understanding HBV infections of humans. The following experiments were successfully completed: (1) Recombinant WHV DNA was transfected into the liver of susceptible woodchucks and acute and chronic WHV infections were produced. The complete nucleotide sequence of the infectious WHV DNA was determined. (2) Serum pools were prepared from chronically infected animals to be used in future experiments. The virus present in these pooled sera represents the equivalent of "plaque purified" virus in our model system. (3) The mutation rate for WHV replication was estimated to be <2 x 10(-4) changes per genome per year, which is lower than the mutation rate of other viruses whose polymerase also lacks an associated proof-reading function. (4) A primary woodchuck hepatocyte tissue culture system was developed for use in transfection experiments.