Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective

Matthieu Foll, Yu Ping Poh, Nicholas Renzette, Anna Ferrer-Admetlla, Claudia Bank, Hyunjin Shim, Anna Sapfo Malaspinas, Gregory Ewing, Ping Liu, Daniel Wegmann, Daniel R. Caffrey, Konstantin B. Zeldovich, Daniel N. Bolon, Jennifer P. Wang, Timothy F. Kowalik, Celia A. Schiffer, Robert W. Finberg, Jeffrey Jensen

Research output: Contribution to journalArticle

60 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere1004185
JournalPLoS Genetics
Volume10
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

Fingerprint

drug resistance
influenza
Population Genetics
Orthomyxoviridae
Drug Resistance
population genetics
Oseltamivir
virus
sialidase
drug
genetic drift
demography
drug therapy
analytical methods
Genetic Drift
Neuraminidase
mutation
drugs
Pharmaceutical Preparations
Human Influenza

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Cancer Research
  • Genetics(clinical)
  • Medicine(all)

Cite this

Foll, M., Poh, Y. P., Renzette, N., Ferrer-Admetlla, A., Bank, C., Shim, H., ... Jensen, J. (2014). Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective. PLoS Genetics, 10(2), [e1004185]. https://doi.org/10.1371/journal.pgen.1004185

Influenza Virus Drug Resistance : A Time-Sampled Population Genetics Perspective. / Foll, Matthieu; Poh, Yu Ping; Renzette, Nicholas; Ferrer-Admetlla, Anna; Bank, Claudia; Shim, Hyunjin; Malaspinas, Anna Sapfo; Ewing, Gregory; Liu, Ping; Wegmann, Daniel; Caffrey, Daniel R.; Zeldovich, Konstantin B.; Bolon, Daniel N.; Wang, Jennifer P.; Kowalik, Timothy F.; Schiffer, Celia A.; Finberg, Robert W.; Jensen, Jeffrey.

In: PLoS Genetics, Vol. 10, No. 2, e1004185, 02.2014.

Research output: Contribution to journalArticle

Foll, M, Poh, YP, Renzette, N, Ferrer-Admetlla, A, Bank, C, Shim, H, Malaspinas, AS, Ewing, G, Liu, P, Wegmann, D, Caffrey, DR, Zeldovich, KB, Bolon, DN, Wang, JP, Kowalik, TF, Schiffer, CA, Finberg, RW & Jensen, J 2014, 'Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective', PLoS Genetics, vol. 10, no. 2, e1004185. https://doi.org/10.1371/journal.pgen.1004185
Foll M, Poh YP, Renzette N, Ferrer-Admetlla A, Bank C, Shim H et al. Influenza Virus Drug Resistance: A Time-Sampled Population Genetics Perspective. PLoS Genetics. 2014 Feb;10(2). e1004185. https://doi.org/10.1371/journal.pgen.1004185
Foll, Matthieu ; Poh, Yu Ping ; Renzette, Nicholas ; Ferrer-Admetlla, Anna ; Bank, Claudia ; Shim, Hyunjin ; Malaspinas, Anna Sapfo ; Ewing, Gregory ; Liu, Ping ; Wegmann, Daniel ; Caffrey, Daniel R. ; Zeldovich, Konstantin B. ; Bolon, Daniel N. ; Wang, Jennifer P. ; Kowalik, Timothy F. ; Schiffer, Celia A. ; Finberg, Robert W. ; Jensen, Jeffrey. / Influenza Virus Drug Resistance : A Time-Sampled Population Genetics Perspective. In: PLoS Genetics. 2014 ; Vol. 10, No. 2.
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