title: Critical role of constitutive type I interferon response in bronchial epithelial cell to influenza infection.
abstract: Innate antiviral responses in bronchial epithelial cells (BECs) provide the first line of defense against respiratory viral infection and the effectiveness of this response is critically dependent on the type I interferons (IFNs). However the importance of the antiviral responses in BECs during influenza infection is not well understood. We profiled the innate immune response to infection with H3N2 and H5N1 virus using Calu-3 cells and primary BECs to model proximal airway cells. The susceptibility of BECs to influenza infection was not solely dependent on the sialic acid-bearing glycoprotein, and antiviral responses that occurred after viral endocytosis was more important in limiting viral replication. The early antiviral response and apoptosis correlated with the ability to limit viral replication. Both viruses reduced RIG-I associated antiviral responses and subsequent induction of IFN-β. However it was found that there was constitutive release of IFN-β by BECs and this was critical in inducing late antiviral signaling via type I IFN receptors, and was crucial in limiting viral infection. This study characterizes anti-influenza virus responses in airway epithelial cells and shows that constitutive IFN-β release plays a more important role in initiating protective late IFN-stimulated responses during human influenza infection in bronchial epithelial cells.
authors.affiliation: Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia. Alan.Hsu@uon.edu.au
authors.forename: Alan C-Y
authors.initials: AC
authors.lastname: Hsu
authors.forename: Kristy
authors.initials: K
authors.lastname: Parsons
authors.forename: Ian
authors.initials: I
authors.lastname: Barr
authors.forename: Sue
authors.initials: S
authors.lastname: Lowther
authors.forename: Deborah
authors.initials: D
authors.lastname: Middleton
authors.forename: Philip M
authors.initials: PM
authors.lastname: Hansbro
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
mesh_terms: D000818:Animals; D017209:Apoptosis; D001980:Bronchi / Q000166:cytology* / Q000821:virology*; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000378:metabolism; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism; D007251:Influenza, Human / Q000378:metabolism*; D007370:Interferon Type I / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism; D008954:Models, Biological; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
chemical_list: D007370:Interferon Type I; D011500:Protein Synthesis Inhibitors; D016899:Interferon-beta; D003513:Cycloheximide; D019158:N-Acetylneuraminic Acid