Abstract
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.
Highlights
Innate immune signaling during early infection constitutes an important line of defense against viruses
The presence of some interferon-stimulating pathogen variants in a given host may be sufficient for triggering innate immune responses, negatively impacting the fitness of interferon-blocking pathogens and posing a major hurdle for the evolution of innate immunity evasion
By allowing for the insulation of interferon-stimulating and interferon-blocking virus variants, spatial structure should play a central role in the evolution of innate immunity evasion
Summary
Innate immune signaling during early infection constitutes an important line of defense against viruses. Innate immunity imposes a strong selective pressure on viruses, which have evolved a variety of evasion mechanisms at the level of viral sensing, signal transduction, and/or gene expression [2,3,4] If successful, these mechanisms lead to avoidance or shutdown of IFN secretion. We have recently shown that a mutant of vesicular stomatitis virus (VSV) that fails to block IFN secretion reduces the fitness of neighbor, IFN-blocking VSV by triggering local antiviral responses [5] This interference defines IFN shutdown as a social trait, since the fitness of a given virus infecting a given cell (focal virus) depends on other members of the viral population (neighborhood). This fitness effect is indirect because it is determined by cells not infected by the focal virus, is exerted through paracrine signaling, and depends on the spatial distribution of infected cells and immunized cells
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