Inhibition of NF-κB activity by the porcine epidemic diarrhea virus nonstructural protein 1 for innate immune evasion

Porcine epidemic diarrhea virus emerged in the US is known to suppress the type I interferons response during infection. In the present study using porcine epithelial cells, we showed that PEDV inhibited both NF-κB and proinflammatory cytokines. PEDV blocked the p65 activation in infected cells and suppressed the PRD II-mediated NF-κB activity. Of the total of 22 viral proteins, nine proteins were identified as NF-κB antagonists, and nsp1 was the most potent suppressor of proinflammatory cytokines. Nsp1 interfered the phosphorylation and degradation of IκBα, and thus blocked the p65 activation. Mutational studies demonstrated the essential requirements of the conserved residues of nsp1 for NF-κB suppression. Our study showed that PEDV inhibited NF-κB activity and nsp1 was a potent NF-κB antagonist for suppression of both IFN and early production of pro-inflammatory cytokines. - Highlights: • PEDV inhibits type I IFNs and NF-κB-mediated pro-inflammatory cytokines. • PEDV blocks p65 nuclear translocation in virus-infected cells. • Among 22 viral proteins, nsp1, nsp3, nsp5, nsp7, nsp14, nsp15, nsp16, ORF3, and E are NF-κB antagonists. • Nsp1 suppresses pro-inflammatory cytokines and p65 activation by blocking IκBα phosphorylation. • The conserved residues of nsp1 are crucial for NF-κB suppression.