title: Ferrets develop fatal influenza after inhaling small particle aerosols of highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1).
abstract: BACKGROUND
  There is limited knowledge about the potential routes for H5N1 influenza virus transmission to and between humans, and it is not clear whether humans can be infected through inhalation of aerosolized H5N1 virus particles. Ferrets are often used as a animal model for humans in influenza pathogenicity and transmissibility studies. In this manuscript, a nose-only bioaerosol inhalation exposure system that was recently developed and validated was used in an inhalation exposure study of aerosolized A/Vietnam/1203/2004 (H5N1) virus in ferrets. The clinical spectrum of influenza resulting from exposure to A/Vietnam/1203/2004 (H5N1) through intranasal verses inhalation routes was analyzed.
  
  
  RESULTS
  Ferrets were successfully infected through intranasal instillation or through inhalation of small particle aerosols with four different doses of Influenza virus A/Vietnam/1203/2004 (H5N1). The animals developed severe influenza encephalomyelitis following intranasal or inhalation exposure to 10¹, 10², 10³, or 10⁴ infectious virus particles per ferret.
  
  
  CONCLUSIONS
  Aerosolized Influenza virus A/Vietnam/1203/2004 (H5N1) is highly infectious and lethal in ferrets. Clinical signs appeared earlier in animals infected through inhalation of aerosolized virus compared to those infected through intranasal instillation.
authors.affiliation: Energy and Life Sciences Division, Midwest Research Institute, 425 Volker Boulevard, Kansas City, Missouri 64110, USA. jlednicky@mriresearch.org
authors.forename: John A
authors.initials: JA
authors.lastname: Lednicky
authors.forename: Sara B
authors.initials: SB
authors.lastname: Hamilton
authors.forename: Richard S
authors.initials: RS
authors.lastname: Tuttle
authors.forename: William A
authors.initials: WA
authors.lastname: Sosna
authors.forename: Deirdre E
authors.initials: DE
authors.lastname: Daniels
authors.forename: David E
authors.initials: DE
authors.lastname: Swayne
mesh_terms: D000336:Aerosols; D000818:Animals; D004195:Disease Models, Animal; D004679:Encephalomyelitis / Q000401:mortality / Q000473:pathology; D005289:Ferrets; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D009976:Orthomyxoviridae Infections / Q000401:mortality* / Q000473:pathology*
chemical_list: D000336:Aerosols