IFIT3 inhibits transmissible gastroenteritis virus (TGEV) infection by promoting the phosphorylation of TBK1 and STAT1, which enhances the innate immune response.

TGEV mainly infects pig small intestinal epithelium, resulting in vomiting, diarrhea, dehydration, and death. IFIT3 is involved in resisting viral infection and is an innate immune regulator. In this study, we determined that TGEV infection could induce IFIT3 expression. The overexpression of IFIT3 inhibited TGEV infection, promoted the phosphorylation of TBK1 and STAT1, and upregulated the transcription of IFN-β and interferon-stimulated genes (ISGs). Conversely, knockdown of IFIT3 decreased the activation of the interferon immune response. Blocking the JAK-STAT1 pathway inhibited the transmission of interferon signals and reversed the restriction of IFIT3 to TGEV infection. Immunoprecipitation revealed that IFIT3 interacted with TBK1 and STAT1, indicating that TBK1 and STAT1 are key molecules through which IFIT3 regulates the interferon immune response and inhibits TGEV infection. This study preliminarily revealed that IFIT3 regulated the innate immune response to inhibit TGEV infection, enriching the theoretical understanding of the interaction between TGEV and the host.