Complex formation of NS5B with NS3 and NS4A proteins of hepatitis C virus.

At present, the mechanism of replication of the HCV genome remains unclear. Recently, NS5B and NS3 of HCV have been shown to exhibit RNA-dependent RNA polymerase and helicase activities, respectively, both of which are indispensable for virus RNA replication. In this study, we examined the complex formation of NS5B with NS3 and NS4A, a cofactor for NS3. We show here that NS5B forms a complex with NS3 through an amino-terminal portion of NS3. The NS3-NS5B complex formation took place both in the presence and absence of NS4A. We also demonstrate that NS5B form a complex with NS4A in the absence of NS3. These results suggest that NS3, NS4A and NS5B interact with each other to form a complex that functions as part of the replication machinery of HCV.