Identifying selection in the within-host evolution of influenza using viral sequence data.

The within-host evolution of influenza is a vital component of its epidemiology. A question of particular interest is the role that selection plays in shaping the viral population over the course of a single infection. We here describe a method to measure selection acting upon the influenza virus wi...

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Main Authors: Christopher J R Illingworth, Andrej Fischer, Ville Mustonen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-07-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1003755
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author Christopher J R Illingworth
Andrej Fischer
Ville Mustonen
author_facet Christopher J R Illingworth
Andrej Fischer
Ville Mustonen
author_sort Christopher J R Illingworth
collection DOAJ
description The within-host evolution of influenza is a vital component of its epidemiology. A question of particular interest is the role that selection plays in shaping the viral population over the course of a single infection. We here describe a method to measure selection acting upon the influenza virus within an individual host, based upon time-resolved genome sequence data from an infection. Analysing sequence data from a transmission study conducted in pigs, describing part of the haemagglutinin gene (HA1) of an influenza virus, we find signatures of non-neutrality in six of a total of sixteen infections. We find evidence for both positive and negative selection acting upon specific alleles, while in three cases, the data suggest the presence of time-dependent selection. In one infection we observe what is potentially a specific immune response against the virus; a non-synonymous mutation in an epitope region of the virus is found to be under initially positive, then strongly negative selection. Crucially, given the lack of homologous recombination in influenza, our method accounts for linkage disequilibrium between nucleotides at different positions in the haemagglutinin gene, allowing for the analysis of populations in which multiple mutations are present at any given time. Our approach offers a new insight into the dynamics of influenza infection, providing a detailed characterisation of the forces that underlie viral evolution.
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spelling doaj-art-12748e2b592849d6aa25cf6089598b502025-08-20T02:22:38ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582014-07-01107e100375510.1371/journal.pcbi.1003755Identifying selection in the within-host evolution of influenza using viral sequence data.Christopher J R IllingworthAndrej FischerVille MustonenThe within-host evolution of influenza is a vital component of its epidemiology. A question of particular interest is the role that selection plays in shaping the viral population over the course of a single infection. We here describe a method to measure selection acting upon the influenza virus within an individual host, based upon time-resolved genome sequence data from an infection. Analysing sequence data from a transmission study conducted in pigs, describing part of the haemagglutinin gene (HA1) of an influenza virus, we find signatures of non-neutrality in six of a total of sixteen infections. We find evidence for both positive and negative selection acting upon specific alleles, while in three cases, the data suggest the presence of time-dependent selection. In one infection we observe what is potentially a specific immune response against the virus; a non-synonymous mutation in an epitope region of the virus is found to be under initially positive, then strongly negative selection. Crucially, given the lack of homologous recombination in influenza, our method accounts for linkage disequilibrium between nucleotides at different positions in the haemagglutinin gene, allowing for the analysis of populations in which multiple mutations are present at any given time. Our approach offers a new insight into the dynamics of influenza infection, providing a detailed characterisation of the forces that underlie viral evolution.https://doi.org/10.1371/journal.pcbi.1003755
spellingShingle Christopher J R Illingworth
Andrej Fischer
Ville Mustonen
Identifying selection in the within-host evolution of influenza using viral sequence data.
PLoS Computational Biology
title Identifying selection in the within-host evolution of influenza using viral sequence data.
title_full Identifying selection in the within-host evolution of influenza using viral sequence data.
title_fullStr Identifying selection in the within-host evolution of influenza using viral sequence data.
title_full_unstemmed Identifying selection in the within-host evolution of influenza using viral sequence data.
title_short Identifying selection in the within-host evolution of influenza using viral sequence data.
title_sort identifying selection in the within host evolution of influenza using viral sequence data
url https://doi.org/10.1371/journal.pcbi.1003755
work_keys_str_mv AT christopherjrillingworth identifyingselectioninthewithinhostevolutionofinfluenzausingviralsequencedata
AT andrejfischer identifyingselectioninthewithinhostevolutionofinfluenzausingviralsequencedata
AT villemustonen identifyingselectioninthewithinhostevolutionofinfluenzausingviralsequencedata