Porcine interferon-induced protein with tetratricopeptide repeats 3, poIFIT3, inhibits swine influenza virus replication and potentiates IFN-β production.

Porcine interferon-induced protein with tetratricopeptide repeats 3 (poIFIT3) is one of the genes most abundantly induced by IFN-α/β and swine influenza virus (SIV). However, little information is available about the role of poIFIT3 in host defense among pigs. In this study, we detected the upregulation of poIFIT3 in porcine alveolar macrophages (PAM) infected with SIV and subsequently cloned poIFIT3 from poly(I:C)-treated PAM cells. The overexpression of poIFIT3 can efficiently suppress the replication of SIV, whereas knockdown of poIFIT3 increases SIV replication. Further experiments on the functional domains showed that the C-terminal of poIFIT3 plays the main role in the antiviral activity of poIFIT3. Moreover, poIFIT3 can significantly enhance poly(I:C)-induced IFN-β promoter activity through both IRF3- and NF-κB-mediated signaling pathways. poIFIT3 potentiates IFN-β production by targeting MAVS, which was further verified by co-immunoprecipitation. This study suggests that poIFIT3 plays a significant role in the clearance of SIV in pigs and potentiates IFN-β production.