Figure 6. Model of FluAPol switching from transcription to replication states.

After virus entry, vRNPs are released and transported into nucleus. To initiate genome replication, the FluAPol would form asymmetric or symmetric dimers with the newly synthesized polymerase. Thus, at early stages, the major Pol II activity is genome transcription that depends on the binding to the Pol II CTD, which facilitates the cap-snatching process. The influenza polymerase core is colored in cyan, the cap binding domain (CBD) in purple, the endonuclease domain (Endo) in pink and Pol II in white. The mRNA transcripts are then translated into viral proteins in the cytoplasm, and then the PA-PB1, PB2, and NS2 are transported to the nucleus to regulate polymerase activity. The domain-swapped NS2 dimer binds to the polymerase and induces the formation of FluAPol-NS2 hexamers to inhibit the transcription process.