Apoptosis Induced By Core Protein Of Hepatitis C Virus

Hepatitis C virus(HCV) is the major causative agent of acute and chronic hepatitis originally identified as non-A non-B hepatitis, which may lead to liver cirrhosis and hepatocellular carcinoma. The molecular mechanism of HCV persistence and pathogenesis is not well understood. So it is important to study the replication of HCV and the functions of all proteins encoded by HCV genome.In order to study the possible functions of HCV core protein in eukaryotic cells, the recombinant plasmid pCDNA3-Core was constructed by inserting HCV-1 core gene(l-574bp) into the site between EcoR I and Xba I, downstream of CMV promoter of eukaryotic expression vector pCDNA3. The recombinant plasmid pCDNA3-Core was transfected to Hela and Cos-7 cell lines by LipoVec? pCDNA3 and pEGFP-N1 as negative and positive control respectively. The expression of core protein in Hela and Cos-7 cell lines was detected by immunofluresence and immunol dot-blot respectively 24hr after transfection. The nuclear cracks in transfected cells was observed by Hoechst 33258 staining and the 180-200bp DNA ladders also was detected 72h after transfection in Cos-7 cell line. These results reveal that HCV Core protein can induce apoptosis in Cos-7 cell.Low virus titre and persistent infection are the major character of HCV-mediated hepatitis, which may be related to the balance between the HCV replication and its host immune system. In our study we have observed that the apoptosis induced by core protein acts very slowly and has a relationship with the amount of core protein expressed. Only when coreprotein accumulates high enough can it has effect on cell growth anddifferentiation leading to apoptosis. Thus HCV can maintain its low virus titre in the infected cells even in the presence of host's immune system. This function of core protein may play an potential critical role in HCV pathogenesis and persistent infection.