A large effective population size for established within-host influenza virus infection
Abstract
Strains of the influenza virus form coherent global populations, yet exist at the level of single infections in individual hosts. The relationship between these scales is a critical topic for understanding viral evolution. Here we investigate the within-host relationship between selection and the stochastic effects of genetic drift, estimating an effective population size of infection Ne for influenza infection. Examining whole-genome sequence data describing a chronic case of influenza B in a severely immunocompromised child we infer an Ne of 2.5 x 107 (95% confidence range 1.0 x 107 to 9.0 x 107) suggesting that genetic drift is of minimal importance during an established influenza infection. Our result, supported by data from influenza A infection, suggests that positive selection during within-host infection is primarily limited by the typically short period of infection. Atypically long infections may have a disproportionate influence upon global patterns of viral evolution.
Data availability
All sequence data is taken from previous publications, and is available from the Sequence Read Archive. Where this is sensible, raw data underlying figures has been made available in files which accompany this document.
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Parallel evolution of influenza across multiple spatiotemporal scalesSRA BioProject, PRJNA364676.
Article and author information
Author details
Funding
Wellcome (101239/Z/13/Z)
- Christopher J R Illingworth
Wellcome (101239/Z/13/A)
- Christopher J R Illingworth
Wellcome (105365/Z/14/Z)
- Casper K Lumby
Isaac Newton Trust
- Christopher J R Illingworth
Helsingin Yliopisto
- Christopher J R Illingworth
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Lumby et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The majority of highly polymorphic genes are related to immune functions and with over 100 alleles within a population, genes of the major histocompatibility complex (MHC) are the most polymorphic loci in vertebrates. How such extraordinary polymorphism arose and is maintained is controversial. One possibility is heterozygote advantage (HA), which can in principle maintain any number of alleles, but biologically explicit models based on this mechanism have so far failed to reliably predict the coexistence of significantly more than ten alleles. We here present an eco-evolutionary model showing that evolution can result in the emergence and maintenance of more than 100 alleles under HA if the following two assumptions are fulfilled: first, pathogens are lethal in the absence of an appropriate immune defence; second, the effect of pathogens depends on host condition, with hosts in poorer condition being affected more strongly. Thus, our results show that HA can be a more potent force in explaining the extraordinary polymorphism found at MHC loci than currently recognized.