Two PDZ binding motifs within NS5 have roles in Tick-borne encephalitis virus replication

► A TBEV replicon model expressing luciferase was constructed. ► Two PDZ binding motifs within NS5 affect TBEV replication. ► Flavivirus NS5 interacts with multiple PDZ domains via C-terminal binding motifs. ► ZO-2 and GIPC interacts with TBEVNS5 in a cellular context.