title: High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B) cells contributes to influenza A virus resistance.
abstract: Respiratory epithelial cells play a key role in influenza A virus (IAV) pathogenesis and host innate response. Transformed human respiratory cell lines are widely used in the study of IAV-host interactions due to their relative convenience, and inherent difficulties in working with primary cells. Transformed cells, however, may have altered susceptibility to virus infection. Proper characterization of different respiratory cell types in their responses to IAV infection is therefore needed to ensure that the cell line chosen will provide results that are of relevance in vivo. We compared replication kinetics of human H1N1 (A/USSR/77) IAVs in normal primary human bronchial epithelial (NHBE) and two commonly used respiratory epithelial cell lines namely BEAS-2B and A549 cells. We found that IAV replication was distinctly poor in BEAS-2B cells in comparison with NHBE, A549 and Madin-Darby canine kidney (MDCK) cells. IAV resistance in BEAS-2B cells was accompanied by an activated antiviral state with high basal expression of interferon (IFN) regulatory factor-7 (IRF-7), stimulator of IFN genes (STING) and IFN stimulated genes (ISGs). Treatment of BEAS-2B cells with a pan-Janus-activated-kinase (JAK) inhibitor decreased IRF-7 and ISG expression and resulted in increased IAV replication. Therefore, the use of highly resistant BEAS-2B cells in IAV infection may not reflect the cytopathogenicity of IAV in human epithelial cells in vivo.
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom.
authors.forename: Lai-Giea
authors.initials: LG
authors.lastname: Seng
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom.
authors.forename: Janet
authors.initials: J
authors.lastname: Daly
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom.
authors.forename: Kin-Chow
authors.initials: KC
authors.lastname: Chang
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Leicestershire, United Kingdom.
authors.forename: Suresh V
authors.initials: SV
authors.lastname: Kuchipudi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001717:Birds; D002478:Cells, Cultured; D004285:Dogs; D015536:Down-Regulation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D009980:Influenza A virus / Q000502:physiology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D000099197:STING Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D050839:Interferon Regulatory Factor-7; D053612:Janus Kinases; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D050791:STAT Transcription Factors; C532857:STING1 protein, human; D000099197:STING Protein