English: IFN evasion strategies of Tick-borne encephalitis virus (TBEV). (A) Passive evasion strategy. Viral NS proteins rearrange the ER membrane and induce replication vesicles or membrane packets. Viral replication and dsRNA is hidden away inside these vesicles as a passive way to prevent PPR recognition (red circle) and upregulation of IFNs. Later in infection, dsRNA leaks out and IFNs are upregulated via IRF3 and IPS-1/MAVS. (B) Left panel: PEPD is needed for maturation and subsequent transport of IFNAR1 to the plasma membrane. IFNAR1 and IFNAR2 heterodimer on plasma membrane can be activated by IFNα/β which leads to the signaling cascade and phosphorylation and translocation of STAT1/2-IRF9 into the nucleus and upregulation of ISGs. Right panel: NS5 interferes with IFN signaling. NS5 protein interacts with PEPD thus preventing IFNAR1 plasma membrane localization (red T). NS5 also prevents STAT1 phosphorylation (red T). Arrows indicate protein transport.