Interferon gamma inhibits transmissible gastroenteritis virus infection mediated by an IRF1 signaling pathway

Interferon gamma (IFN-gamma) is best known for its ability to regulate host immune responses; however, its direct antiviral activity is less well studied. Transmissible gastroenteritis virus (TGEV) is an economically important swine enteric coronavirus and causes acute diarrhea in piglets. At present, little is known about the function of IFN-gamma in the control of TGEV infection. In this study, we demonstrated that IFN-gamma inhibited TGEV infection directly in ST cells and intestine epithelial IPEC-J2 cells and that the anti-TGEV activity of IFN-gamma was independent of IFN-alpha/beta. Moreover, IFN-gamma suppressed TGEV infection in ST cells more efficiently than did IFN-alpha, and the combination of IFN-gamma and IFN-alpha displayed a synergistic effect against TGEV. Mechanistically, using overexpression and functional knockdown experiments, we demonstrated that porcine interferon regulatory factor 1 (poIRF1) elicited by IFN-gamma primarily mediated IFN-gamma signaling cascades and the inhibition of TGEV infection by IFN-gamma. Importantly, we found that TGEV elevated the expression of poIRF1 and IFN-gamma in infected small intestines and peripheral blood mononuclear cells. Thus, IFN-gamma plays a crucial role in curtailing enteric coronavirus infection and may serve as an effective prophylactic and/or therapeutic agent against TGEV infection.