FIGURE 6.

Model of the interrelationship between optimal growth of FluA and FluB viruses and PA binding affinities. Within a certain range of PA binding affinity (between dashed lines), optimal polymerase activity is ensured. However, FluA and FluB acquired substantially different PA binding affinities during independent evolution, resulting in a limited compatibility of the PA-binding domains between virus types. Lower, but also higher, PA binding affinities result in impaired polymerase activity as exemplified by the indicated PB1 mutants. The question mark indicates that FluB PB1 mutants that exhibit higher PA binding affinities and show impaired polymerase activity are not described yet. For further details, see under “Discussion.”