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• W2073800139 startingPage "e1004149" @default.
• W2073800139 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." @default.
• W2073800139 created "2016-06-24" @default.
• W2073800139 creator A5000460408 @default.
• W2073800139 creator A5083653654 @default.
• W2073800139 date "2015-03-18" @default.
• W2073800139 modified "2023-10-15" @default.
• W2073800139 title "Within-Host Stochastic Emergence Dynamics of Immune-Escape Mutants" @default.
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• W2073800139 doi "https://doi.org/10.1371/journal.pcbi.1004149" @default.
• W2073800139 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4365036" @default.
• W2073800139 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25785434" @default.
• W2073800139 hasPublicationYear "2015" @default.
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