Molecular Biology of HBV and HCV Replication

The group has shown the presence of HBV replication proteins, polymerase and X protein within different cytoplasmic compartments as well as the nucleus of HBV infected hepatocytes. We are currently investigating the functions of the proteins during the replication cycle of HBV.

We have developed retroviral and adeno-associated virus (AAV) vectors that can integrate into the genome of HBV producing cell lines and express siRNA molecules that inhibit HBV replication by more than 98%. The development of in vivo models for RNA interference (RNAi) and the investigation of its effects on HBV replication are currently underway.

Our studies on the effects of HCV virus proteins on host cells have shown that, a number of potentially important genes show altered expression and antiviral mechanisms are inhibited by HCV proteins. In particular, we have shown that NS3 can inhibit the antiviral effect of interferon alpha. We are investigating the mechanism of this inhibition by mutational analysis of NS3 protease and helicase activities.

Using an RNA replicon cell line, which we have developed, we have shown that HCV RNA and viral proteins can be reduced by around 98% when a plasmid that expresses a HCV siRNA is introduced. This model is being used to investigate the effects of inhibiting HCV RNA on the formation of virus replication complexes. In addition models for the use of the HCV siRNAi in vivo are being developed.