Synthetic RNA derived from the foot-and-mouth disease virus genome elicits antiviral responses in bovine and porcine cells through IRF3 activation

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly transmissible disease affecting wild and domestic animals including pigs, cattle and sheep. The ability of synthetic RNA transcripts mimicking distinct domains in the non-coding regions of the FMDV genome (ncRNAs) to induce a potent innate immune response in swine cultured cells and mice has been previously described, as well as their enhancing effect on conventional inactivated FMD vaccines. Here, we provide evidence of the activation of interferon regulatory factor 3 (IRF3), a key transcriptional regulator of type I interferon (IFN)-dependent immune responses after transfection of swine and bovine cells with transcripts corresponding to the FMDV 3' non-coding region (3'NCR). Induction of IFN-beta and Mx1 expression, concomitantly with antiviral activity and IRF3 activation was observed in bovine MDBK cells transfected with the 3'NCR. Our results link the stimulation of the innate immune response observed in 3'NCR-transfected cells to the intracellular type I IFN signaling pathway and suggest the potential use of these molecules for antiviral strategies in cattle.