title: Influenza A viruses target type II pneumocytes in the human lung.
abstract: BACKGROUND
  Highly pathogenic avian H5N1 influenza viruses preferentially infect alveolar type II pneumocytes in human lung. However, it is unknown whether this cellular tropism contributes to high viral virulence because the primary target cells of other influenza viruses have not been systematically studied.
  
  
  METHODS
  We provide the first comparison of the replication, tropism, and cytokine induction of human, highly pathogenic avian influenza A virus subtype H5N1 and other animal influenza A viruses in primary human lung organ cultures.
  
  
  RESULTS
  Subytpe H5N1 and human-adapted subtype H1N1 and H3N2 viruses replicated efficiently in the lung tissue, whereas classic swine and low-pathogenicity avian viruses propagated only poorly. Nevertheless, all viruses examined were detected almost exclusively in type II pneumocytes, with a minor involvement of alveolar macrophages. Infection with avian viruses that have a low and high pathogenicity provoked a pronounced induction of cytokines and chemokines, while human and pandemic H1N1-2009 viruses triggered only weak responses.
  
  
  CONCLUSIONS
  These findings show that differences in the pathogenic potential of influenza A viruses in the human lung cannot be attributed to a distinct cellular tropism. Rather, high or low viral pathogenicity is associated with a strain-specific capacity to productively replicate in type II pneumocytes and to cope with the induced cytokine response.
authors: Division of Influenza/Respiratory Viruses, Robert Koch Institut, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. isq8@cdc.gov
authors: Viola K
authors: VK
authors: Weinheimer
authors: Anne
authors: A
authors: Becher
authors: Mario
authors: M
authors: Tönnies
authors: Gudrun
authors: G
authors: Holland
authors: Jessica
authors: J
authors: Knepper
authors: Torsten T
authors: TT
authors: Bauer
authors: Paul
authors: P
authors: Schneider
authors: Jens
authors: J
authors: Neudecker
authors: Jens C
authors: JC
authors: Rückert
authors: Kolja
authors: K
authors: Szymanski
authors: Bettina
authors: B
authors: Temmesfeld-Wollbrueck
authors: Achim D
authors: AD
authors: Gruber
authors: Norbert
authors: N
authors: Bannert
authors: Norbert
authors: N
authors: Suttorp
authors: Stefan
authors: S
authors: Hippenstiel
authors: Thorsten
authors: T
authors: Wolff
authors: Andreas C
authors: AC
authors: Hocke
mesh_terms: D056809:Alveolar Epithelial Cells / Q000145:classification* / Q000821:virology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000145:classification / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000821:virology; D008168:Lung / Q000166:cytology; D016676:Macrophages, Alveolar / Q000821:virology; D046509:Tissue Culture Techniques; D056189:Viral Tropism / Q000502:physiology*; D014774:Virulence; D014779:Virus Replication / Q000502:physiology
chemical_list: D016207:Cytokines