Sir Donna, Liang Chengyu, Chen Wen-ling, Jung Jae U, Ou Jing-hsiung James
Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, California 90033, USA.
Autophagy. 2008 Aug;4(6):830-1. doi: 10.4161/auto.6566. Epub 2008 Jul 8.
Autophagy removes long-lived proteins and damaged organelles and is important for maintaining cellular homeostasis. It can also serve in innate immunity to remove intracellular pathogens. As such, viruses have evolved different mechanisms to subvert this innate immune response. We have recently demonstrated that hepatitis C virus (HCV) can also suppress autophagic protein degradation by suppressing the fusion between autophagosomes and lysosomes. This suppression causes the accumulation of autophagosomes and enhances HCV RNA replication.(1) Our further analysis indicated that the induction of autophagosomes by HCV is dependent on the unfolded protein response (UPR). Our studies thus delineate a molecular pathway by which HCV induces autophagosomes. The prolonged perturbation of the autophagic pathway by HCV likely plays an important role in HCV pathogenesis.
自噬可清除长寿蛋白和受损细胞器，对维持细胞内稳态至关重要。它还可参与固有免疫以清除细胞内病原体。因此，病毒进化出了不同机制来颠覆这种固有免疫反应。我们最近证明，丙型肝炎病毒（HCV）也可通过抑制自噬体与溶酶体之间的融合来抑制自噬蛋白降解。这种抑制导致自噬体积累并增强HCV RNA复制。（1）我们的进一步分析表明，HCV诱导自噬体依赖于未折叠蛋白反应（UPR）。因此，我们的研究描绘了一条HCV诱导自噬体的分子途径。HCV对自噬途径的长期干扰可能在HCV发病机制中起重要作用。
