Specific inhibition of hepatitis B virus replication by sense RNA

We describe effects of sense RNA molecules on hepatitis B virus (HBV) replication and antigen synthesis in transiently transfected cells. When certain subgenomic fragments of HBV were expressed as sense RNA together with a replication-competent genome of HBV, they inhibited HBV replication by up to 75% and HBsAg secretion by up to 60%. The corresponding antisense sequences had a 50% inhibitory effect in one case and no effect in another case. The sense RNA species did not inhibit duck hepatitis B virus (DHBV) replication, suggesting specific inhibitory effects. HBV transcript levels were unaltered in the presence of sense RNA species, consistent with an inhibitory effect mediated at the posttranscriptional level. The inhibition of HBV replication by overexpression of sense RNA derived from the viral genome represents an example of sense cosuppression of an animal virus.