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 performed: (1) The variability of WHV genomes in an infected animal was determined. (2) Serum pools with and without defective virus were found to induce the same percentage of chronic carriers. This suggests that the presence of defective virus in a WHV inoculum is not a prerequisite for the establishment of persistent hepadnavirus infections. (3) Oligonucleotide directed mutagenesis was used to introduce point mutations in the precore and X genes as well as open reading frames 5 and 6 to determine the importance of these genes in virus replication using woodchuck transfection assays. (4) The WHV and HBV X gene promoters were cloned into the vector pSVOCAT to compare promoter strength in human and woodchuck cells. (5) A New York strain of WHV was cloned in preparation for DNA sequencing.