Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
Autophagy. 2011 Nov;7(11):1394-6. doi: 10.4161/auto.7.11.17514. Epub 2011 Nov 1.
Hepatitis C virus (HCV) infects approximately 130 million people worldwide. The clinical sequelae of this chronic disease include cirrhosis, functional failure and carcinoma of the liver. HCV induces autophagy, a fundamental cellular process for maintaining homeostasis and mediating innate immune response, and also inhibits autophagic protein degradation and suppresses antiviral immunity. In addition to this ploy, the HCV serine protease composed of the viral non-structural proteins 3/4A (NS3/4A) can enzymatically digest two cellular proteins, mitochondria-associated anti-viral signaling protein (MAVS) and Toll/interleukin-1 receptor domain containing adaptor inducing IFN-β (TRIF). Since these two proteins are the adaptor molecules in the retinoic acid-inducible gene I (RIG-I) and TLR3 pathways, respectively, their cleavage has been suggested as a pivotal mechanism by which HCV blunts the IFN-α/β signaling and antiviral responses. Thus far, how HCV perturbs autophagy and copes with IFN-α/β in the liver remains unclear.
丙型肝炎病毒（HCV）感染全球约 1.3 亿人。这种慢性疾病的临床后果包括肝硬化、功能衰竭和肝癌。HCV 诱导自噬，这是一种维持体内平衡和介导先天免疫反应的基本细胞过程，也抑制自噬蛋白降解并抑制抗病毒免疫。除了这一策略外，由病毒非结构蛋白 3/4A（NS3/4A）组成的 HCV 丝氨酸蛋白酶还可以酶解两种细胞蛋白，即线粒体相关抗病毒信号蛋白（MAVS）和 Toll/白细胞介素-1 受体域包含衔接诱导 IFN-β（TRIF）。由于这两种蛋白分别是 RIG-I 和 TLR3 途径中的衔接分子，因此它们的切割被认为是 HCV 削弱 IFN-α/β信号和抗病毒反应的关键机制。到目前为止，HCV 如何扰乱自噬并在肝脏中应对 IFN-α/β仍不清楚。
