Within-host stochastic emergence dynamics of immune-escape mutants

Predicting the emergence of new pathogenic strains is a key goal of evolutionary epidemiology. However, the majority of existing studies have focussed on emergence at the population level, and not within a host. In particular, the coexistence of pre-existing and mutated strains triggers a heightened immune response due to the larger total pathogen population; this feedback can smother mutated strains before they reach an ample size and establish. Here, we extend previous work for measuring emergence probabilities in non-equilibrium populations, to within-host models of acute infections. We create a mathematical model to investigate the emergence probability of a fitter strain if it mutates from a self-limiting strain that is guaranteed to go extinct in the long-term. We show that ongoing immune cell proliferation during the initial stages of infection causes a drastic reduction in the probability of emergence of mutated strains; we further outline how this effect can be accurately measu...预测新型致病毒株的出现是进化流行病学的核心研究目标之一。然而，当前绝大多数相关研究均聚焦于种群层面的毒株出现事件，而非宿主内部的演化过程。具体而言，预先存在的毒株与突变毒株共存时，由于病原体总负荷更高，会触发更强的免疫应答；这种免疫反馈可在突变毒株达到足够种群规模并成功定植前，将其抑制乃至清除。本研究将此前针对非平衡种群毒株出现概率的测算方法，拓展至急性感染的宿主内模型场景中。我们构建了一套数学模型，用于分析当高适配度毒株从注定长期灭绝的自限性毒株中突变产生时，该突变毒株的出现概率。研究证实，感染初期阶段持续发生的免疫细胞增殖会大幅降低突变毒株的出现概率；并进一步阐述了如何精准测算这一效应的具体方法……