Aweya Jude Juventus, Sze Ching Wooen, Bayega Anthony, Mohd-Ismail Nur Khairiah, Deng Lin, Hotta Hak, Tan Yee-Joo
Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore.
Department of Microbiology, Yong Loo Lin School of Medicine, National University Health System (NUHS), National University of Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A⁎STAR), Singapore 138673, Singapore.
Virology. 2015 Jan 1;474:41-51. doi: 10.1016/j.virol.2014.10.027. Epub 2014 Nov 13.
Hepatitis C virus (HCV) induces cytopathic effects in the form of hepatocytes apoptosis thought to be resulted from the interaction between viral proteins and host factors. Using pathway specific PCR array, we identified 9 apoptosis-related genes that are dysregulated during HCV infection, of which the BH3-only pro-apoptotic Bcl-2 family protein, BIK, was consistently up-regulated at the mRNA and protein levels. Depletion of BIK protected host cells from HCV-induced caspase-3/7 activation but not the inhibitory effect of HCV on cell viability. Furthermore, viral RNA replication and release were significantly suppressed in BIK-depleted cells and over-expression of the RNA-dependent RNA polymerase, NS5B, was able to induce BIK expression. Immunofluorescence and co-immunoprecipitation assays showed co-localization and interaction of BIK and NS5B, suggesting that BIK may be interacting with the HCV replication complex through NS5B. These results imply that BIK is essential for HCV replication and that NS5B is able to induce BIK expression.
丙型肝炎病毒（HCV）以肝细胞凋亡的形式诱导细胞病变效应，认为这是病毒蛋白与宿主因子相互作用的结果。使用通路特异性PCR芯片，我们鉴定出9个在HCV感染期间失调的凋亡相关基因，其中仅含BH3结构域的促凋亡Bcl-2家族蛋白BIK在mRNA和蛋白水平上持续上调。敲低BIK可保护宿主细胞免受HCV诱导的caspase-3/7激活，但不能保护其免受HCV对细胞活力的抑制作用。此外，在敲低BIK的细胞中，病毒RNA复制和释放受到显著抑制，并且RNA依赖性RNA聚合酶NS5B的过表达能够诱导BIK表达。免疫荧光和免疫共沉淀分析显示BIK与NS5B共定位并相互作用，表明BIK可能通过NS5B与HCV复制复合体相互作用。这些结果表明，BIK对HCV复制至关重要，并且NS5B能够诱导BIK表达。
