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dc.contributor.authorNaughtin, M
dc.contributor.authorDyason, JC
dc.contributor.authorMardy, S
dc.contributor.authorSorn, S
dc.contributor.authorvon Itzstein, M
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.issn0066-4804
dc.identifier.doi10.1128/AAC.01773-10
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherAmerican Society for Microbiology
dc.publisher.placeUnited States
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom2004
dc.relation.ispartofpageto2010
dc.relation.ispartofissue5
dc.relation.ispartofjournalAntimicrobial agents and Chemotherapy
dc.relation.ispartofvolume55
dc.rights.retentionY
dc.subject.fieldofresearchCellular Interactions (incl. Adhesion, Matrix, Cell Wall)
dc.subject.fieldofresearchStructural Biology (incl. Macromolecular Modelling)
dc.subject.fieldofresearchInfectious Agents
dc.subject.fieldofresearchMicrobiology
dc.subject.fieldofresearchMedical Microbiology
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchcode060106
dc.subject.fieldofresearchcode060112
dc.subject.fieldofresearchcode060502
dc.subject.fieldofresearchcode0605
dc.subject.fieldofresearchcode1108
dc.subject.fieldofresearchcode1115
dc.titleNeuraminidase Inhibitor Sensitivity and Receptor-Binding Specificity of Cambodian Clade 1 Highly Pathogenic H5N1 Influenza Virus
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 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.
gro.date.issued2011
gro.hasfulltextFull Text
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorDyason, Jeffrey C.


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