title: Multidrug-resistant 2009 pandemic influenza A(H1N1) viruses maintain fitness and transmissibility in ferrets.
abstract: BACKGROUND
  The 2009 influenza A(H1N1) pandemic called attention to the limited influenza treatment options available, especially in individuals at high risk of severe disease. Neuraminidase inhibitor-resistant seasonal H1N1 viruses have demonstrated the ability to transmit well despite early data indicating that resistance reduces viral fitness. 2009 H1N1 pandemic viruses have sporadically appeared containing resistance to neuraminidase inhibitors and the adamantanes, but the ability of these viruses to replicate, transmit, and cause disease in mammalian hosts has not been fully characterized.
  
  
  METHODS
  Two pretreatment wild-type viruses and 2 posttreatment multidrug-resistant viruses containing the neuraminidase H275Y mutation collected from immunocompromised patients infected with pandemic influenza H1N1 were tested for viral fitness, pathogenicity, and transmissibility in ferrets.
  
  
  RESULTS
  The pretreatment wild-type viruses and posttreatment resistant viruses containing the H275Y mutation all demonstrated significant pathogenicity and equivalent viral fitness and transmissibility.
  
  
  CONCLUSIONS
  The admantane-resistant 2009 pandemic influenza A(H1N1) virus can develop the H275Y change in the neuraminidase gene conferring resistance to both oseltamivir and peramivir without any loss in fitness, transmissibility, or pathogenicity. This suggests that the dissemination of widespread multidrug resistance similar to neuraminidase inhibitor resistance in seasonal H1N1 is a significant threat.
authors.affiliation: Viral Pathogenesis and Evolution Section, Laboratory of Infectious Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. memolim@niaid.nih.gov
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Memoli
authors.forename: A Sally
authors.initials: AS
authors.lastname: Davis
authors.forename: Kathleen
authors.initials: K
authors.lastname: Proudfoot
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Chertow
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Hrabal
authors.forename: Tyler
authors.initials: T
authors.lastname: Bristol
authors.forename: Jeffery K
authors.initials: JK
authors.lastname: Taubenberger
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D024921:Drug Resistance, Multiple, Viral; D005289:Ferrets; D014943:Global Health; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000472:pathogenicity*; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology; D008168:Lung / Q000821:virology; D008297:Male; D009976:Orthomyxoviridae Infections / Q000635:transmission / Q000662:veterinary* / Q000821:virology; D058873:Pandemics; D017201:Virus Shedding
chemical_list: D000998:Antiviral Agents