Influenza virus drug resistance: a time-sampled population genetics perspective.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_0719718A8EE7
Type
Article: article from journal or magazin.
Collection
Publications
Title
Influenza virus drug resistance: a time-sampled population genetics perspective.
Journal
PLoS genetics
Author(s)
Foll M., Poh Y.P., Renzette N., Ferrer-Admetlla A., Bank C., Shim H., Malaspinas A.S., Ewing G., Liu P., Wegmann D., Caffrey D.R., Zeldovich K.B., Bolon D.N., Wang J.P., Kowalik T.F., Schiffer C.A., Finberg R.W., Jensen J.D.
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
02/2014
Peer-reviewed
Oui
Volume
10
Number
2
Pages
e1004185
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
The challenge of distinguishing genetic drift from selection remains a central focus of population genetics. Time-sampled data may provide a powerful tool for distinguishing these processes, and we here propose approximate Bayesian, maximum likelihood, and analytical methods for the inference of demography and selection from time course data. Utilizing these novel statistical and computational tools, we evaluate whole-genome datasets of an influenza A H1N1 strain in the presence and absence of oseltamivir (an inhibitor of neuraminidase) collected at thirteen time points. Results reveal a striking consistency amongst the three estimation procedures developed, showing strongly increased selection pressure in the presence of drug treatment. Importantly, these approaches re-identify the known oseltamivir resistance site, successfully validating the approaches used. Enticingly, a number of previously unknown variants have also been identified as being positively selected. Results are interpreted in the light of Fisher's Geometric Model, allowing for a quantification of the increased distance to optimum exerted by the presence of drug, and theoretical predictions regarding the distribution of beneficial fitness effects of contending mutations are empirically tested. Further, given the fit to expectations of the Geometric Model, results suggest the ability to predict certain aspects of viral evolution in response to changing host environments and novel selective pressures.
Keywords
Bayes Theorem, Drug Resistance, Viral/genetics, Genetic Drift, Genetics, Population, Humans, Influenza A Virus, H1N1 Subtype/drug effects, Influenza A Virus, H1N1 Subtype/genetics, Influenza, Human/genetics, Influenza, Human/virology, Mutation, Oseltamivir/pharmacology, Selection, Genetic
Pubmed
Web of science
Open Access
Yes
Create date
16/06/2019 15:10
Last modification date
07/08/2024 10:27
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