Figure 11. Model explaining the functional mechanism of the UFS switch.
A proposed mechanistic model of flavivirus vRNA replication. (i) After the viral genome is released into the cytoplasm, first, translation occurs on the circularized genome to generate a sufficient level of viral proteins for downstream vRNA synthesis. (ii) Accumulation of viral replication proteins (only NS5 and NS3 are shown) to high concentrations results in the formation of an RNA-viral replicase complex and initiates (−) RNA synthesis to generate the double-stranded replication form (RF). (iii) Then, the synthesis of nascent (+) RNA using RF as the template is initiated by NS5/viral replicase. During the process, 5′ local structures including UFS are formed in the displaced, parental (+) strand RNA. A free NS5/viral replicase is recruited to bind the 5′ end of the displaced (+) RNA. (iv) As soon as the nascent (+) strand RNA synthesis completes, the released (+) ssRNA genome is circularized by terminal interactions, and the next round of (−) strand synthesis is ready to start.