Molecular analysis on the tumorigenicity of hepatitis C virus nonstructural protein NS3

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In order to examine the influence of hepatitis C virus (HCV) NS3 to the cells, we used transfection method using lipofectin. Transfectant containing 5'half sequence of the HCV genome segment encoding NS3 (HCV-NS3-N) rapidly proliferated and formed tumors in nude mice. However, after the cotransfection with tumor suppressor gene p53 transfectants (HCV-NS3-N+p53) did not show any tumorigenicity. The result suggest that HCV-NS3 has some influence to the function of p53. To investigate the interaction between HCV-NS3 and p53, we prepared the fusion-protein GST-HCV-NS3 expressed in the bacteria. In the binding experiment in vitro using cell extracts, we did not detect the binding of NS3 to p53. This does not exclude the possibility of the weak or indirect interaction between HCV-NS3 and p53. Actually we found 90 kDa protein which could bind to HCV-NS3. On the other hand, we tried to find the effective antiviral drug using the replication system of HCV-related virus, i.e. Japanese encephalitis virus (JEV). One of tested reagents, furanonaphtoquinone (FNQ) showed antiviral activity (Takegami et al., 1998). To retard the tumorigenesis by HCV,it is important to inhibit viral replication and some reactions between virus and host cells. Further analyzes on the interaction of HCV-NS3 and host proteins including p53, and mechanism of antiviral effect of FNQ are essential.