| Summary: | 碩士 === 慈濟大學 === 醫學生物技術研究所 === 98 === Infection with hepatitis C virus (HCV) will cause chronic infection, liver cirrhosis, and even hepatocellular carcinoma (HCC). At present, neither an effective treatment for chronic HCV infection nor a vaccine to prevent HCV infection is available. Identification of host factors involved in viral replication is critical for understanding the molecular mechanism of virus replication. Identification of host factors involved in viral replication also facilitates the development of anti-viral agents. Genes differentially expressed (over-expressed or down-regulated) in HuH7 cells with (Replicon cell) or without (RE* cell) HCV sub-genomic replicon were identified by dd-RT-PCR. Genes over-expressed in HCV replicon cells could be the factors facilitating HCV replication while down-regulated genes could be the factors repressing the HCV replication. Heparin cofactor II (HCII) identified by ddRT-PCR was down-regulated in HCV replicon cells. To determine whether HCII represses HCV replication in the HCV replicon systems, both loss-of-function (knockdown of HC II) and gain-of-function (over-expression of HC II) approaches were used. Our results showed HC II could indeed inhibit HCV replication. Furthermore, heparin could reverse the suppressive effect of HC II on HCV replication. HCII represses the HCV replication possibly through interacting with HCV NS3 protein. The binding domains of HCII and HCV NS3 proteins were also determined by yeast two-hybrid system.
In conclusion, our studies suggested HC II could interact with HCV NS3 protein and in turn represses HCV replication. Further studies to characterize the mechanisms how HCV down-regulates the expression of HC II are needed.
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