Rapamycin-induced autophagy restricts porcine epidemic diarrhea virus infectivity in porcine intestinal epithelial cells

Abstract

Porcine epidemic diarrhea virus (PEDV) invades porcine intestinal epithelial cells (IECs) and causes diarrhea and dehydration in pigs. In the present study, we showed a suppression of PEDV infection in porcine jejunum intestinal epithelial cells (IPEC-J2) by an increase in autophagy. Autophagy was activated by rapamycin at a dose that does not affect cell viability and tight junction permeability. The induction of autophagy was examined by LC3I/LC3II conversion. To confirm the autophagic-flux (entire autophagy pathway), autophagolysosomes were examined by an immunofluorescence assay. Pre-treatment with rapamycin significantly restricted not only a 1 h infection but also a longer infection (24 h) with PEDV, while this effect disappeared when autophagy was blocked. Co-localization of PEDV and autophagosomes suggests that PEDV could be a target of autophagy. Moreover, alleviation of PEDV-induced cell death in IPEC-J2 cells pretreated with rapamycin demonstrates a protective effect of rapamycin against PEDV-induced epithelial cell death. Collectively, the present study suggests an early prevention against PEDV infection in IPEC-J2 cells via autophagy that might be an effective strategy for the restriction of PEDV, and opens up the possibility of the use of rapamycin in vivo as an effective prophylactic and prevention treatment.

Nonstructural protein 6 of porcine epidemic diarrhea virus induces autophagy to promote viral replication via the PI3K/Akt/mTOR axis

“…These results were consistent with previous research on PEDV-induced autophagy in Vero cells by Guo X. et al (Guo et al, 2017). However, Ko S. et al reported that PEDV infection is suppressed in IPEC-J2 cells by an increase in autophagy induced by rapamycin (Ko et al, 2017). These different results might occur because of the different degrees of virulence of different PEDV strains.…”

BST2 suppresses porcine epidemic diarrhea virus replication by targeting and degrading virus nucleocapsid protein with selective autophagy

“…It has been reported that autophagy was triggered by the effective replication of PEDV and benefited PEDV replication by using autophagy regulators and RNA interference in Vero cells [31,63]. Still, rapamycin-induced autophagy reduces PEDV infection in porcine IECs [32]. Here, we demonstrated that BST2 and PEDV could induce autophagy in Vero or LLC-PK1 cells, and BST2 could increase the levels of autophagy in cells expressing N protein.…”

“…It has been demonstrated that PEDV utilizes autophagy to facilitate its replication in Vero cells [31]. However, another study suggested that rapamycin-induced autophagy restricted PEDV infectivity in porcine intestinal epithelial cells (IECs) [32]. Therefore, the effects of autophagy on PEDV replication may differ in different cells.…”

Antiviral activity of anisomycin against spring viraemia of carp virus in epithelioma papulosum cyprini cells and zebrafish

“…For instance, dexamethasone, a classic immunosuppressive agent, has been reported with antiviral activity against Human immunodeficiency virus and Parainfluenza virus (Bourinbaiar and Leehuang, 1995;Liliana et al, 2003). Rapamycin, the third-generation immunosuppressive agent, was found with antiviral activity against infectious hematopoietic necrosis virus, rift valley fever virus and so on (Bell et al, 2017;Ko et al, 2017;Zhao et al, 2017). In addition, these immunosuppressive agents usually possess anti-inflammatory activity and can improve pathological features (Attur et al, 2000;Liliana et al, 2003;Song et al, 2015).…”