Tumor suppressor p53 inhibits porcine epidemic diarrhea virus infection via interferon-mediated antiviral immunity

Abstract

A B S T R A C T p53 is a tumor suppressor gene that can be activated in many contexts, such as DNA damage or stressful conditions. p53 has also been shown to be important for responses to certain viral infections. Porcine epidemic diarrhea virus (PEDV) is a major enteric pathogen of the coronavirus family that causes extensive mortality among piglets. The involvement of p53 during PEDV infection has not previously been investigated. In this study, we detected p53 upregulation in response to PEDV infection. Treatment with a p53 specific activator or p53 overexpression markedly decreased viral replication, and we showed that there was more viral progeny produced in p53 knock-out cells than in p53 wild-type cells. Finally, we demonstrated that inhibition of viral infection by p53 was mediated via p53-dependent IFN signaling, leading to IFN-stimulated response element (ISRE) activation, as well as the upregulation of IFN-stimulated genes (ISGs) and IFN-β released from infected cells. These findings demonstrate that p53 suppresses PEDV infection, offering a novel therapeutic strategy for combatting this deadly disease in piglets. as a central regulator of the innate immune response (Rivas et al., https://doi.

P53 in the impaired lungs

“…P53 transactivates interferon regulatory factor 7 (IRF7) to regulate the expression of IFNα and IFNβ. Overexpression of P53 in porcine epidemic diarrhea virus (PEDV) infection, a pathogen from the coronavirus family, negatively regulates viral replication [ 137 ]. Other studies suggested that papain-like proteases (PLPs) may serve as a potential therapeutic target for viral infections [ [138] , [139] , [140] ].…”

Molecular mechanisms and pharmacological interventions in the replication cycle of human coronaviruses

“…SARS-CoV promotes the expression of a truncated form of p53 that inhibits apoptosis mediated by wild-type p53 (Leong et al, 2005). This is supported by the observation that the Porcine epidemic diarrhea virus (PEDV) production is increased in p53 knockout cells (Hao et al, 2019).…”

A tissue- and gender-specific regulation of the SARS-CoV-2 receptor ACE2 by p53 in pigs

“…Little is known about the role of p53 in the regulation of ACE2. An earlier study reported that p53 suppresses the replication of coronavirus through ACE2 degradation in humans [ 23 ] and inhibits the interferon-mediated antiviral immunity in pigs [ 24 ]. In this study, we show that the absence of the p53 binding site increases the activity of ACE2 promoter in porcine kidney cells.…”