Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity.
10.1007/s13238-014-0104-6
- Author:
Xiaojuan CHEN
1
;
Kai WANG
;
Yaling XING
;
Jian TU
;
Xingxing YANG
;
Qian ZHAO
;
Kui LI
;
Zhongbin CHEN
Author Information
1. Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
- Publication Type:Journal Article
- MeSH:
Apoptosis Regulatory Proteins;
antagonists & inhibitors;
genetics;
immunology;
Autophagy;
Beclin-1;
Coronavirus NL63, Human;
genetics;
immunology;
Gene Expression Regulation;
HEK293 Cells;
HeLa Cells;
Host-Pathogen Interactions;
immunology;
Humans;
Immune Evasion;
Immunity, Innate;
Interferon-gamma;
genetics;
immunology;
Lysosomes;
metabolism;
virology;
MCF-7 Cells;
Membrane Fusion;
Membrane Proteins;
antagonists & inhibitors;
genetics;
immunology;
Microtubule-Associated Proteins;
genetics;
immunology;
Papain;
genetics;
immunology;
Phagosomes;
metabolism;
virology;
RNA, Small Interfering;
genetics;
immunology;
Signal Transduction;
Virus Replication
- From:
Protein & Cell
2014;5(12):912-927
- CountryChina
- Language:English
-
Abstract:
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 incomplete autophagy process by increasing the accumulation of autophagosomes but blocking the fusion of autophagosomes with lysosomes. Furthermore, PLP2-TM interacts with the key autophagy regulators, LC3 and Beclin1, and promotes Beclin1 interaction with STING, the key regulator for antiviral IFN signaling. Finally, knockdown of Beclin1 partially reverses PLP2-TM's inhibitory effect on innate immunity which resulting in decreased coronavirus replication. These results suggested that coronavirus papain-like protease induces incomplete autophagy by interacting with Beclin1, which in turn modulates coronavirus replication and antiviral innate immunity.
