dc.contributor.author	Ormond, Louise
dc.contributor.author	Liu, Ping
dc.contributor.author	Matuszewski, Sebastian
dc.contributor.author	Renzette, Nicholas
dc.contributor.author	Bank, Claudia
dc.contributor.author	Zeldovich, Konstantin
dc.contributor.author	Bolon, Daniel N.
dc.contributor.author	Kowalik, Timothy F.
dc.contributor.author	Finberg, Robert W.
dc.contributor.author	Jensen, Jeffrey D.
dc.contributor.author	Wang, Jennifer P.
dc.date.accessioned	2017-09-06T14:20:11Z
dc.date.available	2017-09-06T14:20:11Z
dc.date.issued	2017-07-19
dc.description	This deposit is composed by the main article plus the supplementary materials of the publication.	pt_PT
dc.description.abstract	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.	pt_PT
dc.description.sponsorship	Office of the Assistant Secretary of Defense for Health Affairs - Peer Reviewed Medical Research Program grant: (W81XWH-15-1-0317); Defense Advanced Research Projects Agency (DARPA) Prophecy Program; Defense Sciences Office (DSO), Contract No. HR0011-11-C-0095, and D13AP00041; MediVector; European Research Council (ERC); Fuji Films; Department of Defense.	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	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	pt_PT
dc.identifier.doi	10.1093/gbe/evx138	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.7/785
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	Oxford University Press	pt_PT
dc.relation	W81XWH-15-1-0317	pt_PT
dc.relation	HR0011-11-C-0095	pt_PT
dc.relation	D13AP00041	pt_PT
dc.relation.publisherversion	https://academic.oup.com/gbe/article-lookup/doi/10.1093/gbe/evx138	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by-nc/4.0/	pt_PT
dc.subject	influenza	pt_PT
dc.subject	population genetics	pt_PT
dc.subject	genetic hitchhiking	pt_PT
dc.subject	mutational meltdown	pt_PT
dc.title	The Combined Effect of Oseltamivir and Favipiravir on Influenza A Virus Evolution	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.citation.endPage	1924	pt_PT
oaire.citation.issue	7	pt_PT
oaire.citation.startPage	1913	pt_PT
oaire.citation.title	Genome Biology and Evolution	pt_PT
oaire.citation.volume	9	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT

The Combined Effect of Oseltamivir and Favipiravir on Influenza A Virus Evolution

Files

Original bundle

License bundle

Collections