title: Neuraminidase inhibitor susceptibility of swine influenza A viruses isolated in Germany between 1981 and 2008.
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.
authors.affiliation: School of Medicine, Department of Virology and Antiviral Therapy, Jena University Hospital, Jena, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Bauer
authors.forename: Ralf
authors.initials: R
authors.lastname: Dürrwald
authors.forename: Michael
authors.initials: M
authors.lastname: Schlegel
authors.forename: Kathrin
authors.initials: K
authors.lastname: Pfarr
authors.forename: Dominik
authors.initials: D
authors.lastname: Topf
authors.forename: Nadine
authors.initials: N
authors.lastname: Wiesener
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Dahse
authors.forename: Peter
authors.initials: P
authors.lastname: Wutzler
authors.forename: Michaela
authors.initials: M
authors.lastname: Schmidtke
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005858:Germany; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D057221:Influenza A Virus, H1N2 Subtype / Q000187:drug effects; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects; D009980:Influenza A virus / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009976:Orthomyxoviridae Infections / Q000662:veterinary / Q000821:virology; D053139:Oseltamivir / Q000494:pharmacology*; D013552:Swine; D013553:Swine Diseases / Q000821:virology*; D053243:Zanamivir / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir