Innate immunity plays a critical role in controlling the early stage of a viral infection and its spread into the organism. The efficacy of innate immunity relies on a set of germ-line encoded receptors, belonging to the family of pattern recognition receptors (PRRs), that can bind conserved features of pathogens, collectively called pathogen-associated molecular patterns (PAMPs). In the case of viruses, PAMPs are mainly represented by their nucleic acids. Their recognition by numerous PRRs activates NF-B and IRF3 leading to the production and secretion of type I interferons (IFNs). By using as experimental model constituted by MEFs knock-out for CIKS, we show that the IL-17R adaptor protein CIKS is involved in this process.
CIKS-/- cells produce and secrete lower amount of IFNβ when challenged by nucleic acids that mimic viral DNA or RNA (pA:T and pI:C respectively). This phenotype is reverted when FLAG-CIKS expression is restored in CIKS-/- cells by lentiviral transduction. IFNβ reduction is not due to alterations in its mRNA stability, rather to a differential phosphorylation of IRF3 between wt and CIKS-/- cells. We also found that wt and ΔUbox CIKS, but not E17A mutant, interacts with Stimulator of interferon genes (STING) and influences its ubiquitination via TRAF6. Moreover, this interaction is a consequence of viral stimulation, especially after DNA treatment.
Here, we describe the role of CIKS in the STING-mediated antiviral signaling, its molecular interactors and the dynamics of this pathway
