NS5 protein is known to frequently use multiple strategies to suppress the JAK-STAT signaling pathway and consequently type I IFN response to mammalianNS5. ZIKV inhibits the phosphorylation of STAT1 and leads to degradation of STAT2; JEV, DENV, and WNV antagonize this pathway tooSTAT2 is frequently targeted for NS5-mediated IFN suppression in flaviviruses, so modifications in NS5 could impact host immune response to viral infection. This evidence concerns the gene RAF1 and viral infectious disease.