Interaction between hepatitis C virus protein NS3 and host proteins including p53 which are related with hepatocellular carcinoma.

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In order to examine the tumorigenesity of hepatitis C virus nonstructural protein NS3, here we tried to detect host proteins which were interacted with HCV-NS3. By the 2-hybrid assay using yeast, we found several NS3-binding host proteins from human cDNA library. One of those proteins, SmD indicating high activity in the 2-hybrid assay, was analyzed as follows.(1) GST fusion protein expressed in E.coli could bind to HCV-NS3 in vitro.(2) Their interaction in vivo was also shown in the transfection experiment using mammalian cells.(3) SmD mutant protein deleted at carboxyl termini could not bind to HCV-NS3.(4) SmD protein could bind to 3'end of HCV RNA, but not 5' end. These results indicate that the HCV-NS3 could bind to SmD at the carboxyl termini and affect the function of SmD in the biosynthesis of mRNA.On the process, p53 expression might be influenced. In addition SmD could influence virus RNA replication. To know the biological significance of the interaction between HCV-NS3 and SmD, further analysis is necessary.