Curcumin activates the JAK-STAT signaling pathway to enhance the innate immune response against porcine epidemic diarrhea virus infection in vivo and in vitro

Porcine epidemic diarrhea (PED) is a highly pathogenic infectious disease caused by porcine epidemic diarrhea virus (PEDV), which has caused significant economic losses to the global pig industry. Due to the high mutability of the PEDV genome, the development of effective vaccines or drugs to prevent and control PEDV is still facing great difficulties. In this study, we found that the natural compound curcumin showed effective antiviral activity against PEDV in VERO-E6 and IPEC-J2 cells. The Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) signaling pathway was screened by transcriptomics as a potential innate immune mechanism of IPEC-J2 cells against PEDV infection. For PEDV, a highly pathogenic virus, cellular autoimmune response is not sufficient to fight against its infection. Our results demonstrated that curcumin could exert antiviral effects by enhancing the JAK-STAT cascade reaction mediated by type I interferon IFN-α and IFN-β in IPEC-J2 cells. In vivo experiments further confirmed the protective effect of curcumin on PEDV-infected piglets and its positive regulation of the JAK-STAT signaling pathway. In vivo, curcumin prophylaxis significantly enhanced IFN-α and IFN-β-induced JAK-STAT signaling and the production of interferon-stimulated genes (ISGs), and increased the innate immune response, thus exerting antiviral effects effectively. In conclusion, our data indicate that curcumin can effectively resist PEDV infection in IPEC-J2 cells and piglets, which provides a new reference for the development of anti-PEDV drugs with important application prospects.