Schematic of the model.

(A) The overall model architecture demonstrating the infection of target cells by virions to yield infected cells, within which viral replication results in the production of wild-type (blue) and mutant (red) genomes, leading in turn to the production of virions carrying these genomes. The separation into intracellular and extracellular evolutionary and dynamical scales is highlighted. (B) Representation of genomes as strings of nucleotides. A hypothetical substring of two nucleotides of interest yields 6 different single mutants and 9 double mutants. (C) Schematic of the intracellular model. A virion carrying a genome of type i infects the cell, triggering the replication of genomes from positive-strand (RNAi) to negative-strand (RCi) and vice versa. Mutation can give rise to altered genomes, RNAj and RCj, resulting in the production of virions Vj in addition to Vi. The events are summarized along with their rates in Table 2. (D) Schematic of the extracellular model. Target cells, T, are produced, die, proliferate, and get infected by virions Vj to yield infected cells Ij, which also proliferate, produce progeny virions, and die. The probability of infection and the type of virions produced are determined from the stochastic intracellular model. The parameters used are in Table 1.