Interestingly, although PDCoV/PEDV co-infection showed an earlier up-regulatory effect on TRAF6-mediated canonical NF-κB and IRF7 signaling pathways by up-regulating TLRs as compared with single-PDCoV or -PEDV, only the up-regulation of the proinflammatory cytokines IL1-α, IL1-β, and IL18 was observed by 5 DPI. Here, TRAF6 is linked to coinfection.