WILD-TYPE LEVELS OF PREGENOMIC RNA AND REPLICATION BUT REDUCED PRE-C RNA AND E-ANTIGEN SYNTHESIS OF HEPATITIS-B VIRUS WITH C(1653)-]T, A(1762)-]T AND G(1764)-]A MUTATIONS IN THE CORE PROMOTER

Hepatitis B virus (HBV) isolates with A-1762 to T and G-1764 to A muta tions in the core promoter have been associated with active hepatitis, severe liver disease following liver transplantation, hepatocellular carcinoma and acute fulminant courses-in the latter case combined with a C-1653 to T mutation, In this study, a mutant core promoter region containing the T-1653, T-1762 and A-1764 mutations was placed into the context of a wild-type HBV genome and analysed by transfection. The m utations reduced the level of pre-C mRNA (by 55%) and e-antigen secret ion. In contrast, no significant effects on the levels of pregenome/C and pre-S/S mRNAs, intracellular core, polymerase, and pre-S1/S2 prote ins and secreted S-antigen were observed, The amount of progeny virus DNA in the cells and in the culture medium was increased marginally, i f at all.