Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, CA 92093-0723, USA.
Mol Cell. 2012 Oct 26;48(2):313-21. doi: 10.1016/j.molcel.2012.07.032. Epub 2012 Sep 6.
Innate immunity controls pathogen replication and spread. Yet, certain pathogens, such as Hepatitis C Virus (HCV), escape immune elimination and establish persistent infections that promote chronic inflammation and related diseases. Whereas HCV regulatory proteins that attenuate antiviral responses are known, those that promote inflammation and liver injury remain to be identified. Here, we show that transient expression of HCV RNA-dependent RNA polymerase (RdRp), NS5B, in mouse liver and human hepatocytes results in production of small RNA species that activate innate immune signaling via TBK1-IRF3 and NF-κB and induce cytokine production, including type I interferons (IFN) and IL-6. NS5B-expression also results in liver damage.
先天免疫控制病原体的复制和传播。然而，某些病原体，如丙型肝炎病毒 (HCV)，逃脱了免疫清除，建立了持续性感染，从而促进慢性炎症和相关疾病。虽然已经知道 HCV 调节蛋白会减弱抗病毒反应，但那些促进炎症和肝损伤的蛋白仍有待确定。在这里，我们表明 HCV RNA 依赖性 RNA 聚合酶 (RdRp)、NS5B 的瞬时表达会导致小鼠肝脏和人肝细胞中产生小 RNA 种类，这些小 RNA 种类通过 TBK1-IRF3 和 NF-κB 激活先天免疫信号，并诱导细胞因子的产生，包括 I 型干扰素 (IFN) 和 IL-6。NS5B 的表达也会导致肝损伤。
