Institute for Integrative Systems Biology (I2SysBio), Consejo Superior de Investigaciones Científicas-Universitat de València, València, Spain.
PLoS Comput Biol. 2020 Feb 10;16(2):e1007656. doi: 10.1371/journal.pcbi.1007656. eCollection 2020 Feb.
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.
大多数病毒已经进化出了防止干扰素（IFN）分泌和逃避先天免疫的策略。最近的研究表明，病毒阻止 IFN 分泌可以被视为一种社会特征，因为给定病毒逃避 IFN 介导的免疫的能力取决于邻居病毒的表型。基于这个想法，我们研究了空间结构在先天免疫逃避进化中的作用。为此，我们使用一种空间显式近似值来模拟 IFN 信号转导和病毒传播，该近似值结合了扩散-反应模型和元胞自动机。我们的结果表明，通过旁分泌 IFN 信号，病毒防止 IFN 分泌的益处受到空间结构的强烈影响。因此，基于 IFN 关闭对病毒种群其他成员产生的间接适应度效应，先天免疫逃避可以进化为一种合作甚至利他的特征。我们确定了决定 IFN 介导的免疫逃避是否应该进化的关键因素，例如病毒传播过程中发生的种群瓶颈、细胞感染和 IFN 分泌的相对速度以及介质的扩散特性。
