Abstract 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 intermediate MOIs lead to faster convergence on the SGF. For low MOIs, this effect occurs because of the requirements for infection, whereas for intermediate MOIs this effect is also due to the high levels of variation generated in the genome formula (GF). Third, we explored the conditions under which a bipartite virus could outcompete a monopartite one. As the heterogeneity between environments and specificity of gene-expression requirements for each environment increased, the bipartite virus was more likely to outcompete the monopartite virus. Under some conditions, changes in the GF helped to exclude the monopartite competitor, highlighting the versatility of the GF. Our results show the inextricable relationship between MOI and the SGF, and suggest that under some conditions, the cost of multipartition can be outweighed by its benefits for the rapid tuning of viral gene expression.

中文翻译：

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多方病毒进化建模：基因组公式有助于快速适应异质环境†

摘要 多体病毒具有两个或多个基因组片段，并将不同的片段包装成不同的粒子类型。尽管多分区被认为会为病毒传播带来成本，但其好处尚不清楚。最近的实验工作表明，病毒基因组片段的平衡频率，即设定点基因组公式 (SGF)，可能不平衡且依赖于宿主物种。这些观察结果重新激发了这样一种假设，即基因组片段频率的变化会导致病毒基因表达的变化，这可能是适应性的。在这里，我们通过开发二分病毒感染模型来探索这一假设，从而产生三方面的贡献。首先，我们表明 SGF 取决于细胞感染复数 (MOI)，当感染的要求与针对每个细胞的病毒颗粒产量优化 SGF 发生冲突时。其次，我们发现 SGF 的收敛速度非常快，通常发生在几轮细胞感染中。低和中等 MOI 导致 SGF 上的收敛速度更快。对于低 MOI，这种影响是由于感染的要求而发生的，而对于中等 MOI，这种影响也是由于基因组公式 (GF) 中产生的高水平变异。第三，我们探索了二分病毒可以胜过单分病毒的条件。随着环境之间的异质性和每个环境的基因表达要求的特异性增加，二分病毒更有可能胜过单分病毒。在某些条件下，GF 的变化有助于排除单一竞争者，突出了 GF 的多功能性。我们的结果显示了 MOI 和 SGF 之间密不可分的关系，并表明在某些条件下，多分区的成本可以被其快速调整病毒基因表达的好处所抵消。