Analysis of protein originated in hepatitis C virus NS3 domain

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It is well known that in Japan the relation between continued infection of hepatitis C virus (HCV) and liver cell cancer is high. However, its mechanism is not clear. HCV (Hepacivirus) is known to show the structure same as Flavivirus. Paying an attention to this point, we have examined the function of a NS3 domain of HCV.And we discovered that HCV-NS3 protein appears by transformation ability, and it has tumor formation ability for mouse cell NIH3T3 (J.Virol., 69 : 3893, 1995). Thus, a possibility that HCV-NS3 shows a carcinogenic function for the HCV virus infected cells was suggested. However, this mechanism is unidentified. To study this, we introduced two genes, HCV-NS3 and p53 vectors, simultaneously, into either NIH3T3 cells or KN73 cells (stocked, human liver cells originated). As a result we found that both the cell-increase ability and the ability of the tumor formation in nude mouse were significantly decreased in the HCV-NS3 and p53 vector introduced cells. Then, we did screening of the host proteins, which are able to show an interacting with NS3-N end domain. By the screening, we gathered 8 clones that were positive HCV-NS3 combination. By the gene analysis of these clones, it was found that domains of mRNA of small-nuclear RNP (SmD) were inserted in the clones. In addition, it became clear that the C end domain of this SmD was put together with HCV-NS3. These results suggest that the cell transformation mechanism of HCV-NS3 may correlate closely with the host proteins. In addition, the host proteins connected with HCV-NS3 are suggested to be nuclear proteins.