Silencing of hepatitis a virus replication by RNA interference

Post-transcriptional gene silencing (PTGS) by RNA interference (RNAi) can lead to clearance of viral pathogens, including representatives of the picornavirus family. Recently (Biochem. Biophys. Res. Com., 318:341-345 (2004), we have reported that small RNA duplexes (siRNAs) are able to interfere with genome replication of the hepatitis A virus (HAV), a peculiar member of the Picornaviridae. By comparing RNA silencing of replication competent and incompetent HAV genomes, we now show that viral genome replication is not a pre-requisite for siRNA inhibition. Furthermore, siRNA treatment of HAV-infected cells resulted in a 10000-fold suppression of viral replication. Compared with the silencing effect of the viral replicons, these data suggest that additional stages of viral RNA serve as targets for RNAi during the virus life cycle. Collectively, the results demonstrate the potential usefulness of RNAi to cure severe cases of hepatitis A.