Type III interferons (IFN-λs) play a vital role to maintain the antiviral state of the mucosal epithelial surface in the gut, and in turn, enteric viruses may have evolved to evade the type III IFN responses during infection. To study of the possible immune evasion of porcine epidemic diarrhea virus (PEDV) from type III IFN response, a line of porcine intestinal epithelial cells was developed as a cell model for PEDV replication. IFN-λ1 and IFN-λ3 inhibited the PEDV replication, indicating the anti-PEDV activity of type III IFNs. Of the 21 PEDV proteins, nsp1, nsp3, nsp5, nsp8, nsp14, nsp15, nsp16, ORF3, E, M, and N were found to suppress the type III IFN activities, and the IRF1 signaling mediated the suppression. PEDV specifically inhibited IRF1 nuclear translocation. Peroxisome is the innate antiviral signaling platform for activation of IRF1-mediated IFN-λ production, and peroxisomes were found to decrease in number in PEDV-infected cells. PEDV nsp1 blocked the nuclear translocation of IRF1 and reduced the number of peroxisomes to suppress IRF1-mediated type III IFNs. Mutational studies showed the conserved residues of nsp1 were crucial for IRF1-mediated IFN-λ suppression. Our study for the first time provides the evidence that the porcine enteric virus PEDV downregulates and evades the IRF1-mediated type III IFN responses by reducing the peroxisomes.IMPORTANCEPorcine epidemic diarrhea virus (PEDV) is a highly contagious enteric coronavirus emerged in swine in the US and has caused severe economic losses. PEDV targets the intestinal epithelial cells in the gut, and intestinal epithelial cells selectively induce and respond to the production of type III interferons (IFNs). However, little is known about modulation of type III IFN response by PEDV in the intestinal epithelial cells. In this study, we established a porcine intestinal epithelial cell model for PEDV replication. We found that PEDV inhibited the IRF1-mediated type III IFN production by decreasing the peroxisomes in number in the porcine intestinal epithelial cells. We also demonstrated that the conserved residues in the PEDV nsp1 protein were crucial for IFN suppression. This study for the first time showed the PEDV evasion of type III IFN response in the intestinal epithelial cells. It provides valuable information on the host cell-virus interactions not only for PEDV but also other enteric viral infections in swine.
Nucleocapsid protein from porcine epidemic diarrhea virus isolates can antagonize interferon-λ production by blocking the nuclear factor-κB nuclear translocation
