Koronaviruksen nsp3 on papaiinin kaltaisia proteaaseja PLP, joista PLP2 indusoi vajaan autofagian

Protein Cell. 2014 Dec;5(12):912-27. doi: 10.1007/s13238-014-0104-6. Epub 2014 Oct 15.

Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity.

Chen X¹, Wang K, Xing Y, Tu J, Yang X, Zhao Q, Li K, Chen Z.

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.

PMID:

25311841

PMCID:

PMC4259884

DOI:

10.1007/s13238-014-0104-6

[Indexed for MEDLINE]

Free PMC Article