CHARACTERIZATION OF HEPATITIS-B VIRUS CORE MUTANTS THAT INHIBIT VIRALREPLICATION

We have generated and functionally characterized dominant negative cor e protein variants of the hepadnaviruses to determine their effects on ''wild type'' viral replication. Plasmids expressing these constructs were introduced into hepatoma cell lines by transient transfection an d effects on wild type woodchuck hepatitis virus (WHV) and hepatitis a virus (HBV) replication were evaluated by Southern blot analysis of p urified viral core particles. WHV and HBV constructs expressing a trun cated core protein fused in frame with the C-terminus of the small sur face protein were found to inhibit viral replication by 90-95% due to disruption of the viral nucleocapsid assembly process and preventing e ncapsidation of pregenomic RNA. The antiviral effects were found to be specific for the targeted virus. These results demonstrate that mutan ts of hepadnaviral core protein may represent a novel class of antivir al agents. (C) 1994 Academic Press, Inc.