Medical Microbiology and Immunology

, Volume 201, Issue 1, pp 61–72

Neuraminidase inhibitor susceptibility of swine influenza A viruses isolated in Germany between 1981 and 2008

  • Katja Bauer
  • Ralf Dürrwald
  • Michael Schlegel
  • Kathrin Pfarr
  • Dominik Topf
  • Nadine Wiesener
  • Hans-Martin Dahse
  • Peter Wutzler
  • Michaela Schmidtke
Original Investigation

DOI: 10.1007/s00430-011-0206-1

Cite this article as:
Bauer, K., Dürrwald, R., Schlegel, M. et al. Med Microbiol Immunol (2012) 201: 61. doi:10.1007/s00430-011-0206-1

Abstract

European swine influenza A viruses donated the matrix protein 2 as well as the neuraminidase (NA) gene to pandemic influenza A (H1N1) viruses that emerged in 2009. As a result, the latter became amantadine resistant and neuraminidase inhibitor (NAI) susceptible. These recent developments reflecting the close connection between influenza A virus infection chains in humans and pigs urge an antiviral surveillance within swine influenza A viruses. Here, NAI susceptibility of 204 serologically typed swine influenza A viruses of subtypes H1N1, H1N2, and H3N2 circulating in Germany between 1981 and 2008 was analyzed in chemiluminescence-based NA inhibition assays. Mean 50% inhibitory concentrations of oseltamivir and zanamivir indicate a good drug susceptibility of tested viruses. As found for human isolates, the oseltamivir and zanamivir susceptibility was subtype-specific. So, swine influenza A (H1N1) viruses were just as susceptible to oseltamivir as to zanamivir. In contrast, swine H1N2 and H3N2 influenza A viruses were more sensitive to oseltamivir than to zanamivir. Furthermore, reduction in plaque size and virus spread by both drugs was tested with selected H1N1 and H1N2 isolates in MDCK cells expressing similar amounts of α2.3- and α2.6-linked sialic acid receptors. Data obtained in cell culture-based assays for H1N1 isolates correlated with that from enzyme inhibition assays. But, H1N2 isolates that are additionally glycosylated at Asn158 and Asn163 near the receptor-binding site of hemagglutinin (HA) were resistant to both NAI in MDCK cells. Possibly, these additional HA glycosylations cause a misbalance between HA and NA function that hampers or abolishes NAI activity in cells.

Keywords

Swine influenza A virus Hemagglutinin glycosylation Neuraminidase inhibitors Oseltamivir Zanamivir Resistance In vitro 

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Katja Bauer
    • 1
  • Ralf Dürrwald
    • 2
  • Michael Schlegel
    • 2
  • Kathrin Pfarr
    • 1
  • Dominik Topf
    • 1
  • Nadine Wiesener
    • 1
  • Hans-Martin Dahse
    • 3
  • Peter Wutzler
    • 1
  • Michaela Schmidtke
    • 1
  1. 1.School of Medicine, Department of Virology and Antiviral TherapyJena University HospitalJenaGermany
  2. 2.IDT Biologika GmbH, Am PharmaparkDessau-RoßlauGermany
  3. 3.Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll InstituteJenaGermany

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