Akil Abdellah, Song Peixuan, Peng Juan, Gondeau Claire, Samuel Didier, Gassama-Diagne Ama
Unité 1193, INSERM, F-94800 Villejuif, France.
UMR-S 1193, Université Paris-Saclay, F-94800 Villejuif, France.
Pathogens. 2021 Oct 15;10(10):1327. doi: 10.3390/pathogens10101327.
Chronic hepatitis C virus (HCV) infection often leads to fibrosis and chronic hepatitis, then cirrhosis and ultimately hepatocellular carcinoma (HCC). The processes of the HVC life cycle involve intimate interactions between viral and host cell proteins and lipid metabolism. However, the molecules and mechanisms involved in this tripartite interaction remain poorly understood. Herein, we show that the infection of HCC-derived Huh7.5 cells with HCV promotes upregulation of the protein inhibitor of activated STAT1 (PIAS1). Reciprocally, PIAS1 regulated the expression of HCV core protein and HCV-induced LD accumulation and impaired HCV replication. Furthermore, PIAS1 controlled HCV-promoted septin 9 filament formation and microtubule polymerization. Subsequently, we found that PIAS1 interacted with septin 9 and controlled its assembly on filaments, which thus affected septin 9-induced lipid droplet accumulation. Taken together, these data reveal that PIAS1 regulates the accumulation of lipid droplets and offer a meaningful insight into how HCV interacts with host proteins.
慢性丙型肝炎病毒（HCV）感染常导致纤维化和慢性肝炎，进而发展为肝硬化并最终引发肝细胞癌（HCC）。HCV生命周期过程涉及病毒与宿主细胞蛋白及脂质代谢之间的密切相互作用。然而，这种三方相互作用所涉及的分子和机制仍知之甚少。在此，我们表明，HCV感染肝癌来源的Huh7.5细胞会促进活化STAT1蛋白抑制剂（PIAS1）的上调。反之，PIAS1调节HCV核心蛋白的表达以及HCV诱导的脂滴积累，并损害HCV复制。此外，PIAS1控制HCV促进的septin 9丝形成和微管聚合。随后，我们发现PIAS1与septin 9相互作用并控制其在丝上的组装，从而影响septin 9诱导的脂滴积累。综上所述，这些数据揭示了PIAS1调节脂滴积累，并为HCV与宿主蛋白的相互作用提供了有意义的见解。
