The role of spatial structure in the evolution of viral innate immunity evasion: A diffusion-reaction cellular automaton model

Most viruses have evolved strategies for preventing interferon (IFN) secretion and evading innate immunity. Recent work has shown that viral shutdown of IFN secretion can be viewed as a social trait, since the ability of a given virus to evade IFN-mediated immunity depends on the phenotype of neighbor viruses. Following this idea, we investigate the role of spatial structure in the evolution of innate immunity evasion. For this, we model IFN signaling and viral spread using a spatially explicit approximation that combines a diffusion-reaction model and cellular automaton. Our results indicate that the benefits of preventing IFN secretion for a virus are strongly determined by spatial structure through paracrine IFN signaling. Therefore, innate immunity evasion can evolve as a cooperative or even altruistic trait based on indirect fitness effects that IFN shutdown exerts on other members of the viral population. We identify key factors determining whether evasion from IFN-mediated immunity should evolve, such as population bottlenecks occurring during viral transmission, the relative speed of cellular infection and IFN secretion, and the diffusion properties of the medium.RS was funded by European Research Council (ERC) Consolidator Grant 724519 Vis-a-Vis (erc.europa.eu).Peer reviewe