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Susceptibility of avian influenza viruses of the N6 subtype to the neuraminidase inhibitor oseltamivir.

Abstract
Avian influenza viruses are a source of genetic material that can be transmitted to humans through direct introduction or reassortment. Although there is a wealth of information concerning global monitoring for antiviral resistance among human viruses of the N1 and N2 neuraminidase (NA) subtypes, information concerning avian viruses of these and other NA subtypes is limited. We undertook a surveillance study to investigate the antiviral susceptibility of avian influenza N6 NA viruses, the predominant subtype among wild waterfowl. We evaluated 73 viruses from North American ducks and shorebirds for susceptibility to the NA inhibitor oseltamivir in a fluorescence-based NA enzyme inhibition assay. Most (90%) had mean IC(50) values ranging from <0.01 to 5.0nM; 10% were from 5.1 to 50.0nM; and none were >50.0nM. Susceptibility to oseltamivir remained stable among all isolates collected over approximately three decades (P⩽0.74). Two isolates with I222V NA substitution had moderately reduced susceptibility to oseltamivir in vitro (IC(50), 30.0 and 40.0nM). One field sample was a mixed population containing an avian paramyxovirus (APMV) and H4N6 influenza virus, as revealed by electron microscopy and hemagglutination inhibition assays with a panel of anti-APMV antisera. This highlights the importance of awareness and careful examination of non-influenza pathogens in field samples from avian sources. This study showed that oseltamivir-resistant N6 NA avian influenza viruses are rare, and must be tested both phenotypically and genotypically to confirm resistance.
AuthorsTerri D Stoner, Scott Krauss, Jasmine C M Turner, Patrick Seiler, Nicholas J Negovetich, David E Stallknecht, Sharon Frase, Elena A Govorkova, Robert G Webster
JournalAntiviral research (Antiviral Res) Vol. 93 Issue 3 Pg. 322-9 (Mar 2012) ISSN: 1872-9096 [Electronic] Netherlands
PMID22252168 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Antiviral Agents
  • Enzyme Inhibitors
  • Viral Proteins
  • Oseltamivir
  • NA protein, influenza A virus
  • Neuraminidase
Topics
  • Animals
  • Anseriformes
  • Antiviral Agents (pharmacology)
  • Enzyme Inhibitors (pharmacology)
  • Influenza A virus (classification, drug effects, enzymology, isolation & purification)
  • Influenza in Birds (virology)
  • Microbial Sensitivity Tests
  • Neuraminidase (antagonists & inhibitors)
  • Oseltamivir (pharmacology)
  • Viral Proteins (antagonists & inhibitors)

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