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 

机构地区：[1]Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing 100850, China [2]Department of Immunology, Bengbu Medical College, Bengbu 233030, China [3]Prince of Wales Clinical School, The University of New South Wales, Sydney, NSW 2052, Australia [4]Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA

出　　处：《Protein & Cell》2014年第12期912-927,共16页蛋白质与细胞（英文版）

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.）.

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.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.

关 键 词：CORONAVIRUS papain-like proteaseautophagy antiviral immunity BECLINL STING 

分 类 号：Q523[生物学—生物化学] TS214.2[轻工技术与工程—粮食、油脂及植物蛋白工程]