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dc.contributor.authorNaughtin, M.
dc.contributor.authorDyason, Jeffrey
dc.contributor.authorMardy, S.
dc.contributor.authorSorn, S.
dc.contributor.authorvon Itzstein, Mark
dc.contributor.authorBuchy, P.
dc.date.accessioned2017-08-10T04:20:04Z
dc.date.available2017-08-10T04:20:04Z
dc.date.issued2011
dc.date.modified2012-02-13T05:06:16Z
dc.identifier.issn00664804en_US
dc.identifier.doi10.1128/AAC.01773-10en_US
dc.identifier.urihttp://hdl.handle.net/10072/42471
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.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.languageEnglishen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofpagefrom2004en_US
dc.relation.ispartofpageto2010en_US
dc.relation.ispartofissue5en_US
dc.relation.ispartofjournalAntimicrobial agents and Chemotherapyen_US
dc.relation.ispartofvolume55en_US
dc.rights.retentionYen_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.subject.fieldofresearchcode060106en_US
dc.subject.fieldofresearchcode060112en_US
dc.subject.fieldofresearchcode060502en_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
dc.description.versionPublisheden_US
gro.rights.copyrightCopyright 2011 American Society for Microbiology. The attached file is reproduced here in accordance with the copyright policy of the publisher. Please refer to the journal's website for access to the definitive, published version.en_US
gro.date.issued2011
gro.hasfulltextFull Text


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