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dc.contributor.authorNaughtin, M.en_US
dc.contributor.authorDyason, Jeffreyen_US
dc.contributor.authorMardy, S.en_US
dc.contributor.authorSorn, S.en_US
dc.contributor.authorvon Itzstein, Marken_US
dc.contributor.authorBuchy, P.en_US
dc.description.abstractThe evolution of the highly pathogenic H5N1 influenza virus produces genetic variations that can lead to changes in antiviral susceptibility and in receptor-binding specificity. In countries where the highly pathogenic H5N1 virus is endemic or causes regular epidemics, the surveillance of these changes is important for assessing the pandemic risk. In Cambodia between 2004 and 2010, there have been 26 outbreaks of highly pathogenic H5N1 influenza virus in poultry and 10 reported human cases, 8 of which were fatal. We have observed naturally occurring mutations in hemagglutinin (HA) and neuraminidase (NA) of Cambodian H5N1 viruses that were predicted to alter sensitivity to neuraminidase inhibitors (NAIs) and/or receptor-binding specificity. We tested H5N1 viruses isolated from poultry and humans between 2004 and 2010 for sensitivity to the NAIs oseltamivir (Tamiflu) and zanamivir (Relenza). All viruses were sensitive to both inhibitors; however, we identified a virus with a mildly decreased sensitivity to zanamivir and have predicted that a V149A mutation is responsible. We also identified a virus with a hemagglutinin A134V mutation, present in a subpopulation amplified directly from a human sample. Using reverse genetics, we verified that this mutation is adaptative for human 2,6-linked sialidase receptors. The importance of an ongoing surveillance of H5N1 antigenic variance and genetic drift that may alter receptor binding and sensitivities of H5N1 viruses to NAIs cannot be underestimated while avian influenza remains a pandemic threat.en_US
dc.publisherAmerican Society for Microbiologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalAntimicrobial agents and Chemotherapyen_US
dc.subject.fieldofresearchCellular Interactions (incl. Adhesion, Matrix, Cell Wall)en_US
dc.subject.fieldofresearchStructural Biology (incl. Macromolecular Modelling)en_US
dc.subject.fieldofresearchInfectious Agentsen_US
dc.titleNeuraminidase Inhibitor Sensitivity and Receptor-Binding Specificity of Cambodian Clade 1 Highly Pathogenic H5N1 Influenza Virusen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.hasfulltextNo Full Text

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