This study investigated the expression of HBV genes. In the investigation, a novel phenomenon was found in that the expression of HBV genes on a cloned HBV DNA was inhibited by cotransfection with plasmids containing HBV surface genes. Furthermore, the production of viral particles was also reduced as measured by endogenous DNA polymerase assay. S1 mapping analysis and nuclear run on experiment showed that the inhibition occurred at the RNA level due to a decrease in transcriptional initiation. Both mutational analyses and cycloheximide blockage revealed that the HBV surface proteins were not required for inhibition. The deletion study showed that the nucleotides 129 to 620 on the HBV surface gene sequence and the donor and acceptor site (SD/SA) sequence of SV40 were both required for inhibition activity. Furthermore, there was no anti-sense HBV RNA in the transfected cells. Based on these results, a sense RNA of HBV was proposed as a novel regulator which can inhibit HBV gene expression.
