Figure 3

Mechanism of replicative homeostasis. (A) High concentrations of consensus sequence Env_wt (blue, A) favour high affinity Env_wt:RNA_pol interactions that out-compete variant forms (Env_mt, red), and alter RNA_pol conformation that increase RNA_pol processivity and reduce fidelity, thus increasing the relative output of variant RNAs (red). Subsequent ribosomal (R, green) translation increases concentration of Env_mt (red), relative to Env_wt, reverting the system to equilibrium. Relative excess of Env_mt (B, red) out-compete Env_wt (blue) for interactions with RNA_pol, favouring Env_mt:RNA_pol, and blocking Env_wt:RNA_pol interactions again altering RNA_pol conformation, the Env_mt:RNA_pol complexes decrease RNA_pol processivity and increase fidelity, increasing output of wild-type RNAs. Subsequent increased translation of Env_wt relative to Env_mt restores the equilibrium.