Enzymatic Properties of the Neuraminidase of Seasonal H1N1 Influenza Viruses Provide Insights for the Emergence of Natural Resistance to Oseltamivir 英文参考文献.docVIP

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Enzymatic Properties of the Neuraminidase of Seasonal H1N1 Influenza Viruses Provide Insights for the Emergence of Natural Resistance to Oseltamivir 英文参考文献.doc

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Enzymatic Properties of the Neuraminidase of Seasonal H1N1 Influenza Viruses Provide Insights for the Emergence of Natural Resistance to Oseltamivir 英文参考文献

Opinion EnzymaticPropertiesoftheNeuraminidaseofSeasonal H1N1InfluenzaVirusesProvideInsightsforthe EmergenceofNaturalResistancetoOseltamivir Marie-AnneRameix-Welti1,VincentEnouf2,Fre′de′riqueCuvelier2,PatriciaJeannin2,Sylvievander Werf1,2 * 1Unite′ deGe′ne′tique Mole′culaire des Virus Respiratoires,URA3015 CNRS,EA302 Universite′ Paris Diderot,Paris,France,2NationalInfluenzaCenter(Northern-France), InstitutPasteur,Paris,France Surveillanceoftheantiviralsusceptibil- ityofinfluenzavirusesinEuroperevealed France) from specimens received in the frame of routine surveillance through the GROG sentinel network between weeks 35/2007 and 03/2008 (Table 1) were studied. Using a standard neuraminidase inhibition assay, the IC50 values for oseltamivir ranged from 1.3 to 5.9 nM forsensitivevirusesandweremuchhigher (IC50,624to942nM)forresistantviruses cantly (p,0.001) higher for viruses resis- tant to oseltamivir as compared to sensi- tiveviruses,aspreviouslyreported[11,20]. However, Km values (19.462.9 mM) for the emergence of influenza A(H1N1) viruses naturally resistant to the anti- neuraminidase inhibitor oseltamivir (Ta- miflu) [1]. Currently, resistant viruses are most prevalent in Europe (25%) but less prevalent in the Americas (16%) or the resistant season remained below the Km viruses from the 2007–2008 values (28.062.7 mM; p,0.01) for NC99 and SI06 vaccine strains and sensitive H1N1 isolatesfrompreviousseasons.Analysisof the Vm values showed no significant difference for sensitive as compared to Western Pacific region (4%) [2]. In Europe, the prevalence varies between countries, with highest levels in Norway (66.5%) and France (46.6%) [3]. These frequencies are in sharp contrast with those observed for H1N1 viruses during previousseasons(0to,1%)[4–8]. (Table 1), as previously published [9,10,12,19]. All viruses were sensitive to zanamivir (IC50, 1.2 to 3.0 nM). All resistant viruses harbored the H275Y substitutionintheirN1. resistant viruses from the 2007–20