TARDBP Inhibits Porcine Epidemic Diarrhea Virus Replication through Degrading Viral Nucleocapsid Protein and Activating Type I Interferon Signaling

PEDV refers to the highly contagious enteric coronavirus that has quickly spread globally and generated substantial financial damage to the global swine industry. During virus infection, the host regulates the innate immunity and autophagy process to inhibit virus infection. However, the virus has evolved plenty of strategies with the purpose of limiting IFN-I production and autophagy processes. Here, we identified that TARDBP expression was downregulated via the transcription factor KLF16 during PEDV infection. TARDBP could inhibit PEDV replication through the combination as well as degradation of PEDV-encoded nucleocapsid (N) protein via proteasomal and autophagic degradation pathways and promoted host antiviral innate immune response by inducing IFN expression through the MyD88-TRAF3-IRF3 pathway. In sum, our data identify a novel antiviral function of TARDBP and provide a better grasp of the innate immune response and protein degradation pathway against PEDV infection.