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Volume 18, Number 1—January 2012

Dispatch

Mutations I117V and I117M and Oseltamivir Sensitivity of Pandemic (H1N1) 2009 Viruses

Aeron C. HurtComments to Author , Sook Kwan Leang, David J. Speers, Ian G. Barr, and Sebastian Maurer-Stroh
Author affiliations: World Health Organization Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia (A.C. Hurt, S.K. Leang, I.G. Barr); PathWest Laboratory Medicine, Nedlands, Western Australia, Australia (D.J. Speers); Agency for Science, Technology and Research, Singapore (S. Maurer-Stroh); Ministry of Health, Singapore (S. Maurer-Stroh); Nanyang Technological University, Singapore (S. Maurer-Stroh)

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Table 1

NAI sensitivity of naturally occurring pandemic (H1N1) 2009 virus I117V mutant and I117V, I117M, I117V + H275Y, I117M + H275Y, and H275Y reverse genetics variants*

Pandemic (H1N1) 2009 viruses Mutation Zanamivir
Oseltamivir carboxylate
Peramivir
Mean IC50 ± SD, nmol/L -fold difference† Mean IC50 ±
SD, nmol/L -fold difference† Mean IC50 ± SD, nmol/L -fold difference†
Mean of NAI-sensitive viruses‡ 0.28 ± 0.15 0.45 ± 0.35 0.20 ± 0.10§
A/Perth/504/2010 I117V 0.96 ± 0.28 3 1.63 ± 0.70 4 0.09 ± 0.01 1
RG-WT 0.24 ± 0.05 0.30 ± 0.20 0.09 ± 0.01
RG-I117V I117V 0.54 ± 0.12 2 1.42 ± 0.52 5 0.08 ± 0.02 1
RG-I117M I117M 0.32 ± 0.05 1 0.31 ± 0.06 1 0.11 ± 0.01 1
RG-I117V + H275Y I117V + H275Y 0.44 ± 0.05 2 568.84 ± 54.89 1,896 47.08 ± 32.57 523
RG-I117M + H275Y I117M + H275Y 0.29 ± 0.04 1 163.72 ± 17.76 546 16.12 ± 0.84 179
RG-H275Y H275Y 0.26 ± 0.03 1 195.02 ± 21.05 650 19.72 ± 1.42 219

*NAI, neuraminidase inhibitor; IC50, 50% inhibitory concentration; –, not applicable.
†-fold differences compared with IC50 value of RG-WT, except for A/Perth/504/2010, which was calculated for on the basis of comparison to the mean IC50 of circulating pandemic (H1N1) 2009 viruses.
‡n = 3,334, obtained through World Health Organization Global Influenza Surveillance and Response System, April 2009–June 2011.
§Mean and SD of peramivir IC50 values were based on analysis of 273 isolates. RG strains were derived by using site-directed mutagenesis and reverse genetics. Mean IC50 ± SD values of the A/Perth/504/2010 virus and the RG strains were calculated on the basis of values derived from 3 independent assays.

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