The HBV-producing human hepatoblastoma cell line, 2.2.15, has been shown to be an accurate model of chronic cellular viral infection and a predictive model of antiviral response for in vivo hepadnaviral infection. Our laboratory has utilized the 2.2.15 cell line in a standardized assay to examine treatment schemes which use combinations of clinically relevant nucleoside analogues, novel methods to deliver potentially useful nucleoside combinations, and treatments which simultaneously target different parts of the HBV replication pathway. For example, the combination of 3TC (lamivudine) with either alpha interferon or penciclovir significantly enhances the antiviral effectiveness of these agents against HBV replication in 2.2.15 cell culture.