| Summary: | 碩士 === 國立臺灣大學 === 微生物學研究所 === 89 === Absctract
Hepatitis C virus (HCV) is the major causative agent of non-A, non-B hepatitis. Alfa interferon (IFN-α) and ribavirin combination therapy is currently the only effective therapy for hepatitis C. However, it only works on less than 50% of the patients. HCV infection often causes persistence in 50-80% of the patitients, 30% of them will eventually progress to cirrhosis and hepatocellular carcinoma. Therefore, it’s important to understand the mechanisms of the pathogenesis and chronicity of HCV infection.
The major function of HCV core protein is to serve as a component of nucleocapsid. However, it has been demonstrated that HCV core protein could regulate gene expression of host cell, induce cell transformation, and influence cell apoptosis. Apoptosis represents one of the abilities of host immunities to clear virus. So, core protein may be an important factor participating in the process of HCV persistent infection.
We evaluated the effects of HCV core protein on the apoptosis induced by the apoptotic inducing agents from TNF-superfamily. Two hepatima cell lines, HuH-7 and HepG2, were used. It was found that HCV core protein sensitized the HuH-7 cells to the α-Fas-, TNF-α-, and TRAIL-mediated apoptosis. The sensitization is less obvious in the α-Fas-induced apoptosis, but much more significant in the TNFα- or TRAIL-induced apoptosis. However, the phenomenon was not observed in core-expression HepG2 cells. Analysis of caspase activities in the apoptotic cells indicated that both caspase 8 and 3, but not caspase 9, activities were enhanced, thus excluding the possibility that the apoptosis is through the mitochondria-mediated pathway. Further Western blot analysis for the expression of FADD, FLICE, and FLIP indicated that the core protein did not affect the levels of these molecules. These results may suggest the HCV core protein sensitize the HuH-7 cells to the TNFα-or TRAIL-mediated apoptosis by enhancing the activation of the apoptosis-related complexes.
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