dc.contributor.authorButler, Jeff
dc.contributor.authorHooper, Kathryn A.
dc.contributor.authorPetrie, Stephen
dc.contributor.authorLee, Raphael
dc.contributor.authorMaurer-Stroh, Sebastian
dc.contributor.authorReh, Lucia
dc.contributor.authorGuarnaccia, Teagan
dc.contributor.authorBaas, Chantal
dc.contributor.authorXue, Lumin
dc.contributor.authorVitesnik, Sophie
dc.contributor.authorLeang, Sook-Kwan
dc.contributor.authorMcVernon, Jodie
dc.contributor.authorKelso, Anne
dc.contributor.authorBarr, Ian G.
dc.contributor.authorMcCaw, James M.
dc.contributor.authorBloom, Jesse D.
dc.contributor.authorHurt, Aeron C.
dc.contributor.editorPerez, Daniel R.*
dc.identifier.citationButler, J., Hooper, K. A., Petrie, S., Lee, R., Maurer-Stroh, S., Reh, L., et al. (2014). Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses. PLoS Pathogens, 10(4), e1004065-.en_US
dc.description.abstractOseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide.en_US
dc.relation.ispartofseriesPLoS pathogensen_US
dc.rights© 2014 Butler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectDRNTU::Science::Biological sciences::Microbiology::Virology
dc.titleEstimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza virusesen_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.versionPublished versionen_US

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