Fig. 2.

Schematic of evasion of the host immune response by flavivirus NS1. Schematic representation of the mechanisms utilized by flaviviruses NS1 to inhibit the immune response. Viral components of flaviviruses were sensed via RIG-I and TLR3/4/7/8. TLR3 and TLR4/7/8 recruit TRIF and MyD88 adaptor respectively, while RIG-I interacts with MAVS adaptor. These adaptors were then activate downstream TBK1 and IKKε kinases, which then leads to phosphorylation of IRF3. The phosphorylated IRF3 translocates to the nucleus, thus inducing the production of type I IFNs. NS1 of ZIKV inhibits IFN-β production by preventing TBK1 phosphorylation, and promotes the clevage of cGAS by inhibiting the proteasomal degradation of caspase-1. JEV NS1′ inhibits the production of IFN-β by reducing MAVS expression. NS1 of WNV interact with RIG-I and MDA5 receptors and degrade their expression to inhibit IFN-β production, and simultaneously to inhibit TLR3-mediated IFN-β expression. DENV NS2B directly target cGAS and causing its degradation.