Journal article

Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1) pdm09 Influenza Viruses

Jeff Butler, Kathryn A Hooper, Stephen Petrie, Raphael Lee, Sebastian Maurer-Stroh, Lucia Reh, Teagan Guarnaccia, Chantal Baas, Lumin Xue, Sophie Vitesnik, Sook-Kwan Leang, Jodie McVernon, Anne Kelso, Ian G Barr, James M McCaw, Jesse D Bloom, Aeron C Hurt

PLOS PATHOGENS | PUBLIC LIBRARY SCIENCE | Published : 2014

Abstract

Oseltamivir 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 ..

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Grants

Awarded by Australian Research Council Future Fellowship


Awarded by NIAID of the National Institutes of Health


Awarded by Victorian Life Sciences Computation Initiative (VLSCI)


Awarded by A*STAR Singapore


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. JMM is supported by an Australian Research Council Future Fellowship (FT110100250) and the Defence Science Institute. JM is supported by a National Health and Medical Research Council Career Development Fellowship. Funding for this research was also kindly provided by the University of Melbourne Research Grants Support Scheme. JDB and KAH were supported by a grant from the NIAID of the National Institutes of Health under award K22AI093789. The authors acknowledge use of computing resources for the quantification of within-host fitness provided by the NeCTAR research cloud (an Australian Government project conducted as part of the Super Science initiative and financed by the Education Investment Fund) and by the Victorian Life Sciences Computation Initiative (VLSCI), grant number VR0274, on its Peak Computing Facility at the University of Melbourne (an initiative of the Victorian Government, Australia.). This work was partially supported by the Australian NHMRC and A*STAR Singapore through the joint grant 12/1/06/24/5793 to ACH and SMS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.