Neuraminidase Inhibitor Sensitivity and Receptor-Binding Specificity of Cambodian Clade 1 Highly Pathogenic H5N1 Influenza Virus

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Title Neuraminidase Inhibitor Sensitivity and Receptor-Binding Specificity of Cambodian Clade 1 Highly Pathogenic H5N1 Influenza Virus
Author Naughtin, M.; Dyason, Jeffrey Clifford; Mardy, S.; Sorn, S.; von Itzstein, Mark; Buchy, P.
Journal Name Antimicrobial Agents and Chemotherapy
Year Published 2011
Place of publication United States
Publisher American Society for Microbiology
Abstract The 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1128/AAC.01773-10
Volume 55
Issue Number 5
Page from 2004
Page to 2010
ISSN 0066-4804
Date Accessioned 2011-12-20; 2012-02-13T05:06:16Z
Date Available 2012-02-13T05:06:16Z
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Cellular Interactions (incl Adhesion, Matrix, Cell Wall); Infectious Agents; Structural Biology (incl Macromolecular Modelling)
URI http://hdl.handle.net/10072/42471
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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