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

为了检测丙型肝炎病毒非结构蛋白NS3的致瘤性，我们尝试检测与丙型肝炎病毒NS3相互作用的宿主蛋白。通过酵母双杂交实验，我们从人的cDNA文库中发现了几种与NS3结合的宿主蛋白。结果表明：(1)在大肠杆菌中表达的GST融合蛋白在体外能与丙型肝炎病毒NS3结合；(2)哺乳动物细胞转染实验表明，两者在体内存在相互作用；(3)缺失羧基末端的SMD突变蛋白不能与丙型肝炎病毒NS3结合。(4)SMD蛋白能与丙型肝炎病毒RNA的3‘端结合，但不能与5’端结合。这些结果表明，丙型肝炎病毒NS3可以与SMD的羧基末端结合，影响SMD在mRNA生物合成中的功能，从而可能影响P53的表达。此外，SMD还可影响病毒RNA的复制。要了解丙型肝炎病毒NS3与SMD相互作用的生物学意义，还需要进一步的分析。

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.