AIMS Deguelin, a natural compound derived from Mundulea sericea (Leguminosae) and some other plants exhibits an activity to inhibit autophagy, a cellular machinery required for hepatitis C virus (HCV) replication. This study aimed to illuminate the impact of deguelin on HCV replication and mechanism(s) involved. METHODS HCV JFH-1-Huh7 infectious system was used for the investigation. Real time RT-PCR, Western blot, fluorescent microscopy assay were used to measure the expression levels of viral or cellular factors. Overexpression and silencing expression techniques were used to determine the role of key cellular factors. RESULTS Deguelin treatment of Huh7 cells significantly inhibited HCV JFH-1 replication in a dose- and time-dependent manner. Deguelin treatment suppressed autophagy in Huh7 cells, evidenced by the decrease of LC3B-II levels, the conversion of LC3B-I to LC3B-II, and the formation of GFP-LC3 puncta as well as the increase of p62 level in deguelin-treated cells compared with control cells. HCV infection could induce autophagy which was also suppressed by deguelin treatment. Mechanism research reveals that deguelin inhibited expression of Beclin1, which is a key cellular factor for the initiation of the autophagosome formation in autophagy. Overexpression or silencing expression of Beclin1 in deguelin-treated Huh7 cells could weaken or enhance the inhibitory effect on autophagy by deguelin, respectively, and thus partially recover or further inhibit HCV replication correspondingly. CONCLUSIONS Deguelin may serve as a novel anti-HCV compound via its inhibitory effect on autophagy, which warrants further investigation as a potential therapeutic agent for HCV infection.

中文翻译：

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Deguelin通过下调人肝癌细胞中Beclin1表达的表达来抑制细胞自噬，从而抑制HCV复制。

AIMS Deguelin是一种天然的化合物，它来自Mundulea sericea（豆科）和其他一些植物，具有抑制自噬的活性，自噬是丙型肝炎病毒（HCV）复制所必需的细胞机制。这项研究旨在阐明地精蛋白对HCV复制和所涉及机制的影响。方法采用HCV JFH-1-Huh7感染系统进行调查。实时RT-PCR，蛋白质印迹，荧光显微镜法用于测量病毒或细胞因子的表达水平。过表达和沉默表达技术用于确定关键细胞因子的作用。结果Deguelin处理Huh7细胞以剂量和时间依赖性显着抑制HCV JFH-1复制。Deguelin处理抑制了Huh7细胞的自噬，这可通过LC3B-II水平的降低来证明，与对照细胞相比，deguelin处理的细胞中LC3B-I向LC3B-II的转化以及GFP-LC3点的形成以及p62水平的增加。HCV感染可诱导自噬，而deguelin治疗也可抑制自噬。机制研究表明，杜格琳可以抑制Beclin1的表达，而Beclin1是自噬中自噬体形成的关键细胞因子。Beclin1在Deguelin处理的Huh7细胞中的过表达或沉默表达可能分别减弱或增强Deguelin对自噬的抑制作用，从而相应地部分恢复或进一步抑制HCV复制。结论Deguelin可能通过对自噬的抑制作用而成为一种新型的抗HCV化合物，因此有必要进一步研究其作为HCV感染的潜在治疗剂。