Figure 2.

Cascade of events that leads to interferons (IFN) mediated antiviral response. The blue pathway leads to the phosphorylation and nuclear translocation of IRF3 thus activating the transcription of the IFN1 and IFN3 genes. This allows the secretion of both IFNs followed by the binding to their respective receptors leading to the activation of the JAK1/TYK2 pathway (depicted in orange). This is followed by the formation of the tripartite transcription factor (ISGF3) complex thus activating interferon stimulated response elements (ISRE) sites resulting in an effective antiviral response (depicted in green). After STAT2 degradation, STAT1 phosphorylation and homo-dimerization increases leading to the formation of gamma activated factor (GAF) elements and up-regulation of IRF1 [44]. This leads to the up-regulation of pro-inflammatory cytokines. ZIKV NS5 interferes at the steps colored in yellow; NS5 binds to TBK1 preventing its phosphorylation and activation by the TRAF’s and also binds STAT2 marking it for proteasomal degradation [26,27,45].