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 autophag...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.展开更多
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.）.
文摘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.
基金This work was supported by the National Natural Science Foundation of China （No. 30571909） the Youth Teacher Foundation of Jiangsu Province （No. BU134701）+1 种基金 Medical Development Foundation of Soochow University （No. EE 134615） We also thank Jin-Sheng YANG for his help in polishing the English language.
