Comprehensive analysis on genes and molecular pathways in host cells associated with Hepatitis C virus infection using next-generation sequencing technology

本研究的目的是阐明宿主细胞中与丙型肝炎病毒（HCV）感染的生命周期相关的分子途径，包括HCV的进入和复制。基因表达数据的综合微阵列分析和层次聚类显示，与脂质代谢的分子途径相关的基因的表达在表达HCV复制子的宿主细胞中显著增加。此外，对HCV-NS 4 B蛋白与细胞干扰素（IFN）介导的抗病毒信号传导之间的相互作用的分析阐明了NS 4 B特异性结合STING，并且NS 4 B抑制STING介导的IFN产生。这些结果表明，我们探索了HCV与宿主信号蛋白之间的新的相互作用，与HCV复制有关。破坏这种相互作用可能会成为根除HCV的一种新的治疗策略。

The objective of this research project is to clarify the molecular pathways in host cells related to life cycle of Hepatitis C virus (HCV) infection, including entry and replication of HCV. Comprehensive microarray analysis and hierarchical clustering of gene expression data revealed that the expressions of genes related to molecular pathways of lipid metabolism are significantly increased in host cells expressing HCV replicon. Furthermore, analysis on the interaction between HCV-NS4B protein and cellular interferon (IFN)-mediated antiviral signaling clarified that NS4B specifically binds STING, and that NS4B suppresses STING-mediated IFN production. These results showed that we explored the new interaction between HCV and host signal protein related to HCV replication. Disruption of that interaction could constitute a novel therapeutic strategy forthe eradication of HCV.