title: Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity.
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.
authors.affiliation: Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Yaling
authors.initials: Y
authors.lastname: Xing
authors.forename: Jian
authors.initials: J
authors.lastname: Tu
authors.forename: Xingxing
authors.initials: X
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D001343:Autophagy; D000071186:Beclin-1; D058957:Coronavirus NL63, Human / Q000235:genetics / Q000276:immunology*; D000086882:Coronavirus Papain-Like Proteases; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008247:Lysosomes / Q000378:metabolism / Q000821:virology; D061986:MCF-7 Cells; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000276:immunology*; D010206:Papain / Q000235:genetics / Q000276:immunology*; D010588:Phagosomes / Q000378:metabolism / Q000821:virology; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014779:Virus Replication; D000099197:STING Protein
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D000086882:Coronavirus Papain-Like Proteases; D007371:Interferon-gamma; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010206:Papain; D034741:RNA, Small Interfering; C491997:BECN1 protein, human; C477012:MAP1LC3A protein, human; C532857:STING1 protein, human; D000099197:STING Protein