Coronavirus membrane-associated papain-like proteases induce autophagy through interacting with Beclin1 to negatively regulate antiviral innate immunity
Protein & Cell
; (12): 912-927, 2014.
Article
em En
| WPRIM
| ID: wpr-757631
Biblioteca responsável:
WPRO
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.
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Autofagia
/
Virologia
/
Replicação Viral
/
Fagossomos
/
Células HeLa
/
Papaína
/
Transdução de Sinais
/
Regulação da Expressão Gênica
/
Interferon gama
/
RNA Interferente Pequeno
Limite:
Humans
Idioma:
En
Revista:
Protein & Cell
Ano de publicação:
2014
Tipo de documento:
Article