Recovery of Influenza B Virus with the H 273 Y Point Mutation in the neuraminidase Active 1 site from a Human Patient

Recovery of Influenza B Virus with the H273Y Point Mutation in the neuraminidase Active 1 site from a Human Patient 2 Rachel R. Higgins, * Melissa Beniprashad, 1 Eddie Chong-King, 1 Yan Li, 5 Nathalie Bastien, 3 Donald E. Low 1,2,3 and Jonathan B. Gubbay 1,2, 4 4 1 Public Health Ontario, 81 Resources Road, Toronto M9P 3T1, Canada 5 2 University of Toronto, Ontario, Canada 6 3 Mount Sinai Hospital, Toronto 7 4 The Hospital for Sick Children, Toronto, Ontario, Canada 8 5 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba 9 *Corresponding author: Rachel R. Higgins, Public Health Ontario, 81 Resources Rd, Toronto, 10 ON M9P 3T1, Canada; Phone: 416-235-6042; Fax: 416-235-6550; email: 11 [email protected] 12 13 The H275Y oseltamivir resistance mutation confers high level resistance to oseltamivir in 14 isolates of human A/H1N1 influenza. We report the recovery and identification of an influenza 15 B virus with the H273Y neuraminidase point mutation directly from a human patient. The 16 H273Y influenza B isolate is resistant to oseltamivir and peramivir but sensitive to zanamivir. 17 18 Resistance to oseltamivir is conferred on seasonal and pandemic A/H1N1 neuraminidase (NA) 19 by a histidine-to-tyrosine mutation at position 275 (corresponds to 273 in B and 274 in N2 NA 20 amino acid numbering) which causes a structural change in the protein active site that weakens 21 the binding of oseltamivir (5). Although initially rare, this mutation became prevalent in 22 clinical samples from treated patients during the 2007-2008 influenza season. Seasonal 23 Copyright © 2012, American Society for Microbiology. All Rights Reserved. J. Clin. Microbiol. doi:10.1128/JCM.00682-12 JCM Accepts, published online ahead of print on 25 April 2012