Fig. 4: Adaptive mutations on the IAV replication platform.
a Overall assembly of IAV replication platform (without ANP32B), mapping mammalian FluPolA adaptations potentially affecting either ANP32B binding or FluPolR–FluPolE interactions. Mutations in PA are highlighted in red; PB2 adaptations in green. See also Supplementary Table 2. b Close-up view of adaptive cluster including PB2 residues 591, 627, 630 and 631, and their interactions with ANP32B residues 151, 154 and 156. c Close-up view of potential adaptive cluster on the FluPolE–FluPolR PA–PA interface. Residue 383 of FluPolE already is aspartate in wildtype Tky05 FluPolA. Also shown is a pair of adaptations found in human-adapted H5N1 FluPolA, namely S388R (FluPolE) and A448E (FluPolR). d Model for the role of ANP32 proteins in the assembly of the IAV replication platform. Upon nuclear entry (1), vRNP-associated FluPolA docks onto the CTD of RNAP II for primary transcription (2). Viral mRNAs are translated in the cytoplasm and newly synthesised FluPol enters the nucleus (3), where it associates with ANP32 and adopts an encapsidating conformation (4). The RNA-free FluPolE–ANP32 complex then associates with vRNP-associated FluPol, stabilising it in a replicase conformation (FluPolR) and forming a replication platform (5).
