Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/785
Título: The Combined Effect of Oseltamivir and Favipiravir on Influenza A Virus Evolution
Autor: Ormond, Louise
Liu, Ping
Matuszewski, Sebastian
Renzette, Nicholas
Bank, Claudia
Zeldovich, Konstantin
Bolon, Daniel N.
Kowalik, Timothy F.
Finberg, Robert W.
Jensen, Jeffrey D.
Wang, Jennifer P.
Palavras-chave: influenza
population genetics
genetic hitchhiking
mutational meltdown
Data: 19-Jul-2017
Editora: Oxford University Press
Citação: Louise Ormond, Ping Liu, Sebastian Matuszewski, Nicholas Renzette, Claudia Bank, Konstantin Zeldovich, Daniel N. Bolon, Timothy F. Kowalik, Robert W. Finberg, Jeffrey D. Jensen, Jennifer P. Wang; The Combined Effect of Oseltamivir and Favipiravir on Influenza A Virus Evolution, Genome Biology and Evolution, Volume 9, Issue 7, 1 July 2017, Pages 1913–1924, https://doi.org/10.1093/gbe/evx138
Resumo: Influenza virus inflicts a heavy death toll annually and resistance to existing antiviral drugs has generated interest in the development of agents with novel mechanisms of action. Favipiravir is an antiviral drug that acts by increasing the genome-wide mutation rate of influenza A virus (IAV). Potential synergistic benefits of combining oseltamivir and favipiravir have been demonstrated in animal models of influenza, but the population-level effects of combining the drugs are unknown. In order to elucidate the underlying evolutionary processes at play, we performed genome-wide sequencing of IAV experimental populations subjected to serial passaging in vitro under a combined protocol of oseltamivir and favipiravir. We describe the interplay between mutation, selection, and genetic drift that ultimately culminates in population extinction. In particular, selective sweeps around oseltamivir resistance mutations reduce genome-wide variation while deleterious mutations hitchhike to fixation given the increased mutational load generated by favipiravir. This latter effect reduces viral fitness and accelerates extinction compared with IAV populations treated with favipiravir alone, but risks spreading both established and newly emerging mutations, including possible drug resistance mutations, if transmission occurs before the viral populations are eradicated.
Descrição: This deposit is composed by the main article plus the supplementary materials of the publication.
Peer review: yes
URI: http://hdl.handle.net/10400.7/785
DOI: 10.1093/gbe/evx138
Versão do Editor: https://academic.oup.com/gbe/article-lookup/doi/10.1093/gbe/evx138
Aparece nas colecções:ED- Artigos

Ficheiros deste registo:
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Ormond_GenomeBiolEvol._2017.pdfmain article913,64 kBAdobe PDFVer/Abrir
Ormond_GenomeBiolEvol._2017-SM1.pdfsupplementary material 1245,06 kBAdobe PDFVer/Abrir
Ormond_GenomeBiolEvol._2017-SM2.xlsxsupplementary material 294,89 kBMicrosoft Excel XMLVer/Abrir


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