Ursodeoxycholic acid against TGEV infection via the JAK-STAT1 signaling pathway.

Abstract

Transmissible gastroenteritis virus (TGEV) causes transmissible gastroenteritis (TGE), leading to severe diarrhea, vomiting, and dehydration in pigs. Mortality rates among newborn piglets are particularly alarming, causing significant economic losses to the livestock industry. In the absence of effective antiviral drugs, developing novel antiviral agents is crucial. Ursodeoxycholic acid (UDCA), as a hydrophilic endogenous bile acid, plays a key role in regulating bile acid metabolism and treating hepatobiliary diseases. Studies indicate that UDCA exhibits specific antiviral effects against the novel coronavirus. Through validation using Western Blot, qPCR, and IFA techniques, we found that UDCA significantly downregulated TGEV N gene copy number, protein levels, viral load, and nuclear translocation in IPEC-J2 cells. Negative staining electron microscopy revealed that UDCA disrupted the structural integrity of TGEV viral particles. In vivo experiments confirmed that UDCA effectively alleviated TGEV infection symptoms and improved piglet survival rates. Data indicate that UDCA exhibits potent antiviral activity against the TGEV Miller strain. Transcriptomic analysis and validation elucidated its mechanism of action: UDCA significantly activates the TLR3-IRF3 signaling axis, induces IFN-λ3 secretion, activates the JAK-STAT1 pathway, and upregulates transcription of downstream interferon-stimulated genes (ISGs). These synergistic effects collectively establish a defense barrier against TGEV invasion and exert antiviral efficacy.