NS5 of TBEV, JEV, WNV, ZIKV, DENV activates RANTES expression in human glioblastoma cells (and also primary astrocytes for TBEV NS5). TBEV NS5 upregulates RIG-I and MDA5 and, due to its RdRp activity, upregulates the phosphorylation of IRF3 and induces its translocation to the nucleus and binding to ISRE of RANTES promoter. This evidence concerns the gene IRF3 and glioblastoma.