Journal article
In vitro generation of neuraminidase inhibitor resistance in A(H5N1) influenza viruses
AC Hurt, JK Holien, IG Barr
Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2009
DOI: 10.1128/AAC.00334-09
Abstract
To identify mutations that can arise in highly pathogenic A(H5N1) viruses under neuraminidase inhibitor selective pressure, two antigenically different strains were serially passaged with increasing levels of either oseltamivir or zanamivir. Under oseltamivir pressure, both A(H5N1) viruses developed a H274Y neuraminidase mutation, although in one strain the mutation occurred in combination with an I222M neuraminidase mutation. The H274Y neuraminidase mutation reduced oseltamivir susceptibility significantly (900- to 2,500-fold compared to the wild type). However the dual H274Y/I222M neuraminidase mutation had an even greater impact on resistance, with oseltamivir susceptibility reduced signi..
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Awarded by Australian National Health and Medical Research Council
Funding Acknowledgements
This study was supported by Australian National Health and Medical Research Council award 400595. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health and Ageing.We thank Robert Shaw, WHO Collaborating Centre for Reference and Research on Influenza, Melbourne, Australia, for experimental assistance; Deborah Middleton and Sue Lowther, Australian Animal Health Laboratory, for provision of laboratory space during the virus growth experiments; and Michael Parker, St. Vincent's Institute of Medical Research, for assistance with structural modeling.