High basal expression of interferon-stimulated genes in human bronchial epithelial (BEAS-2B) cells contributes to influenza A virus resistance

PLoS One. 2014 Oct 14;9(10):e109023. doi: 10.1371/journal.pone.0109023. eCollection 2014.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Birds
  • Cells, Cultured
  • Dogs
  • Down-Regulation / drug effects
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / virology
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A virus / physiology
  • Interferon Regulatory Factor-7 / genetics
  • Interferon Regulatory Factor-7 / metabolism
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / metabolism
  • Madin Darby Canine Kidney Cells
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • STAT Transcription Factors / antagonists & inhibitors
  • STAT Transcription Factors / metabolism
  • Virus Replication / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • Interferon Regulatory Factor-7
  • Membrane Proteins
  • Protein Kinase Inhibitors
  • STAT Transcription Factors
  • STING1 protein, human
  • Janus Kinases

Grants and funding

This project is funded by a Ministry of Higher Education, Government of Malaysia PhD scholarship awarded to LS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.