Figure 6

Dynamic progression of RNA_pol functional properties, processivity () and fidelity () predicted by replicative homeostasis. Initial state (A, corresponding to panel A, Figure 7): in a newly infected cell, high-affinity wild-type:RNA_pol interactions will predominate resulting in high RNA_pol processivity but low fidelity causing high-level viraemia with broad virus phenotypic spectrum, maximizing cell tropism. Intracellular accumulation of variant viral proteins (B, c.f. panel B, Figure 7) reduces RNA_pol processivity but increases fidelity reducing viral RNA synthesis and consequently, viraemia before a dynamic, fluctuating equilibrium (C, c.f. panel C or D, Figure 7) develops in which inhibition of RNA_pol by variant viral proteins is balanced by increases in RNA_pol fidelity (with consequent synthesis of wild-type viral products tending to cause high RNA_pol processivity).