Journal article
Predicting Permissive Mutations That Improve the Fitness of A(H1N1)pdm09 Viruses Bearing the H275Y Neuraminidase Substitution
R Farrukee, V Gunalan, S Maurer-Stroh, PC Reading, AC Hurt
Journal of Virology | Published : 2022
DOI: 10.1128/jvi.00918-22
Open access
Abstract
Oseltamivir-resistant influenza viruses arise due to amino acid mutations in key residues of the viral neuraminidase (NA). These changes often come at a fitness cost; however, it is known that permissive mutations in the viral NA can overcome this cost. This result was observed in former seasonal A(H1N1) viruses in 2007 which expressed the H275Y substitution (N1 numbering) with no apparent fitness cost and lead to widespread oseltamivir resistance. Therefore, this study aims to predict permissive mutations that may similarly enable fit H275Y variants to arise in currently circulating A(H1N1)pdm09 viruses. The first approach in this study utilized in silico analyses to predict potentially per..
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Awarded by National Medical Research Council
Funding Acknowledgements
We thank Rebecca Bowyer, Thomas Cumming, Anthony Gomes, Simone Azzopardi, Charlene Plasencia, and Danijela Krmek at the Bio-resource facility of University of Melbourne for providing assistance in animal handling. We also thank Michelle Wille for assisting in establishing the bioinformatics analysis and Leo Lee for providing assistance with animal experiments. Finally, this project would not have been possible without the generous support and guidance of Jesse Bloom whose protocols and pipelines were utilized heavily throughout the manuscript for creating and analyzing virus libraries. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. Authors Sebastian MaurerStorh acknowledges support by NMRC grant MOH-OFIRG19nov-0013/MOH-000565-00. We declare no competing interests.