The Study Of The Genetic Variation And T Cell Response Of Hepatitis C Virus Non-structural 3 Region

Hepatitis C virus(HCV) was a major etiologic agent of most non-A,non-B hepatitis, more than 170 million of the world's population is infected,most of them will develop to chronic hepatitis , cirrhosis and hepatocelluar carcinoma. It is crucial to study the pathogenesis of HCV infection, and develop an efficient vaccine. So the first aim of this study is to investigate the genetic variation of NS3 region of hepatitis C virus (HCV) and the role of variant epitope in HCV infection, the second is to find an conserved epitope for designing vaccine and the role of DNA-vaccine in HCV infection. There are five parts in this study.1 The dynamic research of genetic variation of the gene of C terminal in HCV NS3 region. Serum samples containing the gene of C terminal of HCV NS3 region from two chronic HCV patients (coded 291 and 941 respectively) during 5 and 3 years and one person recovered from HCV infection (coded 681) were amplified by RT-PCR, then sequenced, five clones were sequenced each year, totally 30 clones, The results of this study demonstrated that there were some characteristics in genetic variation of C terminal of HCV NS3 region. 1 .The sequences of genes of C terminal of HCV NS3 region were highly conserved. More than 89 percent nucleotides were same in all sequences, more than 92 percent similarity was found comparing with reference sequence (HC-HB isolation). The similarity in same year at the same patient was more than 96 percent.2 The sequences of amino acid were also highly conserved in all sequences, no insert, delete mutation was found. Only one terminal code was found in one sequence, and the amino acid sequence of the site cleaved by the NS3 serine protease, demonstrating the importance of HCV NS3 domain in HCV replicate and process. 3 The clones of 291 patient exist in cross manner, no obvious dominant clones were found. Dominant clones drift was found in 941 patient. 2. The study of the of CTL response of C terminal in HCV NS3 region. Long-term evolution of NS3 C-terminal protein containing the predicted CTL...