Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards

Anna Gillman, Shaman Muradrasoli, Hanna Söderström, Fredrik Holmberg, Neus Latorre-Margalef, Conny Tolf, Jonas Waldenström, Gunnar Gunnarsson, Björn Olsen, Josef D Järhult

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Influenza A virus (IAV) has its natural reservoir in wild waterfowl and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate (OC)), stockpiled as Tamiflu® for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may there exert evolutionary pressure on avian IAV in waterfowl, resulting in development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo Mallard (Anas platyrhynchos) study we tested if an OC-resistant avian IAV strain (A(H1N1)/NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected Mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission in 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV, induced by OC exposure of the natural host, can persist in absence of the drug. Thus, there is a risk that human pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir resistant pandemic IAV would be a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment and resistance surveillance of IAV in wild birds.

Original languageEnglish
Pages (from-to)2378-2383
Number of pages5
JournalApplied and Environmental Microbiology
Volume81
Issue number7
DOIs
Publication statusPublished - 2015

Swedish Standard Keywords

  • Microbiology (10606)
  • Other Basic Medicine (30199)

Keywords

  • DNA analysis
  • microbiota
  • peri-implantitis

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