Porcine IKKe is involved in the STING-induced type I IFN antiviral response of the cytosolic DNA signaling pathway.

The cyclic GMP-AMP synthase and stimulator of interferon (IFN) genes (cGAS-STING) pathway serves as a crucial component of innate immune defense and exerts immense antiviral activity by inducing the expression of type I IFNs. Currently, STING-activated production of type I IFNs has been thought to be mediated only by TANK-binding kinase 1 (TBK1). Here, we identified that porcine IKKe (pIKKe) is also directly involved in STING-induced type I IFN expression and antiviral response by using IKKe -/- porcine macrophages. Similar to pTBK1, pIKKe interacts directly with pSTING on the C-terminal tail. Furthermore, the TBK1-binding motif of pSTING C-terminal tail is essential for its interaction with pIKKe, and within the TBK1-binding motif, the leucine (L) 373 is also critical for the interaction. On the other hand, both kinase domain and scaffold dimerization domain of pIKKe participate in the interactions with pSTING. Consistently, the reconstitution of pIKKe and its mutants in IKKe -/- porcine macrophages corroborated that IKKe and its kinase domain and scaffold dimerization domain are all involved in the STING signaling and antiviral function. Thus, our findings deepen the understanding of porcine cGAS-STING pathway, which lays a foundation for effective antiviral therapeutics against porcine viral diseases. [ABSTRACT FROM AUTHOR]