Please use this identifier to cite or link to this item: https://doi.org/10.1128/JVI.01657-16
Title: Deep sequencing of influenza A virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification
Authors: Leonard, A.S
McClain, M.T
Smith, G.J.D 
Wentworth, D.E
Halpin, R.A
Lin, X
Ransier, A
Stockwell, T.B
Das, S.R
Gilbert, A.S
Lambkin-Williams, R
Ginsburg, G.S
Woods, C.W
Koelle, K
Keywords: virus hemagglutinin
virus nucleoprotein
virus RNA
Article
controlled study
disease course
genetic distance
genetic variation
human
human experiment
Influenza A virus
Influenza A virus (H3N2)
inoculation
molecular evolution
nasal lavage fluid
next generation sequencing
nonhuman
normal human
priority journal
quantitative analysis
virus gene
animal
biological model
chicken
genetic selection
genetic variation
genetics
growth, development and aging
high throughput sequencing
influenza
virology
virus genome
zygote
Animals
Chickens
Evolution, Molecular
Genetic Variation
Genome, Viral
High-Throughput Nucleotide Sequencing
Humans
Influenza A Virus, H3N2 Subtype
Influenza, Human
Models, Genetic
RNA, Viral
Selection, Genetic
Zygote
Issue Date: 2016
Publisher: American Society for Microbiology
Citation: Leonard, A.S, McClain, M.T, Smith, G.J.D, Wentworth, D.E, Halpin, R.A, Lin, X, Ransier, A, Stockwell, T.B, Das, S.R, Gilbert, A.S, Lambkin-Williams, R, Ginsburg, G.S, Woods, C.W, Koelle, K (2016). Deep sequencing of influenza A virus from a human challenge study reveals a selective bottleneck and only limited intrahost genetic diversification. Journal of Virology 90 (24) : 11247-11258. ScholarBank@NUS Repository. https://doi.org/10.1128/JVI.01657-16
Rights: Attribution 4.0 International
Abstract: Knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. Here, we analyze a unique viral data set of next-generation sequencing (NGS) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with cell- and egg-passaged virus. Nasal wash samples collected from 7 of these subjects were successfully deep sequenced. From these, we characterized changes in the subjects' viral populations during infection and identified differences between the virus in these samples and the viral stock used to inoculate the subjects. We first calculated pairwise genetic distances between the subjects' nasal wash samples, the viral stock, and the influenza virus A/Wisconsin/67/2005 (H3N2) reference strain used to generate the stock virus. These distances revealed that considerable viral evolution occurred at various points in the human challenge study. Further quantitative analyses indicated that (i) the viral stock contained genetic variants that originated and likely were selected for during the passaging process, (ii) direct intranasal inoculation with the viral stock resulted in a selective bottleneck that reduced nonsynonymous genetic diversity in the viral hemagglutinin and nucleoprotein, and (iii) intrahost viral evolution continued over the course of infection. These intrahost evolutionary dynamics were dominated by purifying selection. Our findings indicate that rapid viral evolution can occur during acute influenza infection in otherwise healthy human hosts when the founding population size of the virus is large, as is the case with direct intranasal inoculation. © 2016, American Society for Microbiology. All Rights Reserved.
Source Title: Journal of Virology
URI: https://scholarbank.nus.edu.sg/handle/10635/179610
ISSN: 0022-538X
DOI: 10.1128/JVI.01657-16
Rights: Attribution 4.0 International
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