title: Published sequences do not support transfer of oseltamivir resistance mutations from avian to human influenza A virus strains.
abstract: BACKGROUND
  Tamiflu (oseltamivir phosphate ester, OE) is a widely used antiviral active against influenza A virus. Its active metabolite, oseltamivir carboxylate (OC), is chemically stable and secreted into wastewater treatment plants. OC contamination of natural habitats of waterfowl might induce OC resistance in influenza viruses persistently infecting waterfowl, and lead to transfer of OC-resistance from avian to human influenza. The aim of this study was to evaluate whether such has occurred.
  
  
  METHODS
  A genomics approach including phylogenetic analysis and probability calculations for homologous recombination was applied on altogether 19,755 neuraminidase (N1 and N2) genes from virus sampled in humans and birds, with and without resistance mutations.
  
  
  RESULTS
  No evidence for transfer of OE resistance mutations from avian to human N genes was obtained, and events suggesting recombination between human and avian influenza virus variants could not be traced in the sequence material studied.
  
  
  CONCLUSIONS
  The results indicate that resistance in influenza viruses infecting humans is due to the selection pressure posed by the global OE administration in humans rather than transfer from avian influenza A virus strains carrying mutations induced by environmental exposure to OC.
authors.affiliation: Department of Infectious Diseases and Virology, Sahlgrenska Academy, University of Göteborg, Guldhedsgatan 10 B, S-413 46, Gothenburg, Sweden. peter.norberg@gu.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Norberg
authors.affiliation: Department of Infectious Diseases and Virology, Sahlgrenska Academy, University of Göteborg, Guldhedsgatan 10 B, S-413 46, Gothenburg, Sweden. magnus.lindh@microbio.gu.se.
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
authors.affiliation: Department of Infectious Diseases and Virology, Sahlgrenska Academy, University of Göteborg, Guldhedsgatan 10 B, S-413 46, Gothenburg, Sweden. sigvard.olofsson@microbio.gu.se.
authors.forename: Sigvard
authors.initials: S
authors.lastname: Olofsson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001717:Birds; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics; D005585:Influenza in Birds / Q000821:virology*; D007251:Influenza, Human / Q000821:virology*; D009154:Mutation; D009439:Neuraminidase / Q000235:genetics; D053139:Oseltamivir / Q000031:analogs & derivatives* / Q000494:pharmacology; D010802:Phylogeny; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D014874:Water Pollutants, Chemical; D053139:Oseltamivir; D009439:Neuraminidase; C535162:oseltamivir carboxylate