title: Within-host stochastic emergence dynamics of immune-escape mutants.
abstract: 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 measured. Further analysis of the model shows that, in the short-term, mutant strains that enlarge their replication rate due to evolving an increased growth rate are more favoured than strains that suffer a lower immune-mediated death rate ('immune tolerance'), as the latter does not completely evade ongoing immune proliferation due to inter-parasitic competition. We end by discussing the model in relation to within-host evolution of human pathogens (including HIV, hepatitis C virus, and cancer), and how ongoing immune growth can affect their evolutionary dynamics.
authors.affiliation: Laboratoire MIVEGEC (UMR CNRS 5290, IRD 224, UM1, UM2), 911 avenue Agropolis, Montpellier, France.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hartfield
authors.affiliation: Laboratoire MIVEGEC (UMR CNRS 5290, IRD 224, UM1, UM2), 911 avenue Agropolis, Montpellier, France.
authors.forename: Samuel
authors.initials: S
authors.lastname: Alizon
mesh_terms: D019295:Computational Biology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007239:Infections / Q000276:immunology*; D008954:Models, Biological; D015233:Models, Statistical; D009154:Mutation / Q000276:immunology*