Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclinl to negatively regulate antiviral innate immunity

作     者：Xiaojuan Chen Kai Wang Yaling Xing Jian Tu Xingxing Yang Qian Zhao Kui Li Zhongbin Chen 

作者机构：Division of Infection and Immunity Department of Electromagnetic and Laser Biology Beijing Institute of Radiation Medicine Beijing 100850 China Department of Immunology Bengbu Medical College Bengbu 233030 China Prince of Wales Clinical School The University of New South Wales Sydney NSW 2052 Australia Department of Microbiology Immunology and Biochemistry University of Tennessee Health Science Center Memphis TN 38163 USA 

出 版 物：《Protein & Cell》 (蛋白质与细胞（英文版）)

年 卷 期：2014年第5卷第12期

页      面：912-927页

核心收录：

学科分类：071010[理学-生物化学与分子生物学] 081704[工学-应用化学] 07[理学] 08[工学] 0710[理学-生物学] 0831[工学-生物医学工程（可授工学、理学、医学学位）] 1007[医学-药学(可授医学、理学学位)] 0832[工学-食品科学与工程（可授工学、农学学位）] 1002[医学-临床医学] 0817[工学-化学工程与技术] 0703[理学-化学] 083202[工学-粮食、油脂及植物蛋白工程] 0836[工学-生物工程] 

基　　金：This research was supported by grants from the National Natural Science Foundation of China (Grant Nos. 81273231 81172799 to Z. C. and 81102478  81471947 to Y. X.) 

主　　题：coronavirus papain-like proteaseautophagy antiviral immunity Beclinl STING 

摘      要：Autophagy plays important roles in modulating viral replication and antiviral immune response. Coronavirus infection is associated with the autophagic process, however, little is known about the mechanisms of autophagy induction and its contribution to coronavirus regulation of host innate responses. Here, we show that the membrane-associated papain-like protease PLP2 （PLP2-TM） of coronaviruses acts as a novel autophagy- inducing protein. Intriguingly, PLP2-TM induces incom- plete autophagy process by increasing the accumula- tion of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2- TM interacts with the key autophagy regulators, LC3 and Beclinl, and promotes Beclinl interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclinl partially reverses PLP2-TM＇s inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results sug- gested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclinl, which in turn modulates coronavirus replication and antiviral innate immunity.