Modeling multipartite virus evolution: the genome formula facilitates rapid adaptation to heterogeneous environments

Multipartite viruses have two or more genome segments, and package different segments into different particle types. Although multipartition is thought to have a cost for virus transmission, its benefits are not clear. Recent experimental work has shown that the equilibrium frequency of viral genome segments, the setpoint genome formula (SGF), can be unbalanced and host-species dependent. These observations have reinvigorated the hypothesis that changes in genome-segment frequencies can lead to changes in virus-gene expression that might be adaptive. Here we explore this hypothesis by developing models of bipartite virus infection, leading to a threefold contribution. First, we show that the SGF depends on the cellular multiplicity of infection (MOI), when the requirements for infection clash with optimizing the SGF for virus-particle yield per cell. Second, we find that convergence on the SGF is very rapid, often occurring within a few cellular rounds of infection. Low and inter...