Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways

Yin Chen, Edward Hamati, Pak Kei Lee, Wai Ming Lee, Shinichiro Wachi, David Schnurr, Shigeo Yagi, Gregory Dolganov, Homer Boushey, Pedro Avila, Reen Wu

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86 Scopus citations

Abstract

Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because the epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway disease is associated with the perturbation of airway epithelial gene expression. In this study, well differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group). Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix Genechip, and changes of the gene expression were confirmed by real-time RT-PCR analysis. At 24 h after infection, 48 genes induced by both viruses were identified. Most of these genes are related to the IFN pathway, and have been documented to have antiviral functions. Indeed, a significant stimulation of IFN-β secretion was detected after RV16 infection. Neutralizing antibody specific to IFN-β and a specific inhibitor of the Janus kinase pathway both significantly blocked the induction of RV-inducible genes. Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA-dependent protein kinase, could block both IFN-β production and RV-induced gene expression. Thus, IFN-β-dependent pathway is a part of the double-stranded RNA-initiated pathway that is responsible for RV-induced gene expression. Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production. Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of an epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations.

Original languageEnglish (US)
Pages (from-to)192-203
Number of pages12
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume34
Issue number2
DOIs
StatePublished - Feb 2006

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Keywords

  • Airway epithelium
  • Gene expression
  • Rhinovirus
  • Transcriptional profiling

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Chen, Y., Hamati, E., Lee, P. K., Lee, W. M., Wachi, S., Schnurr, D., Yagi, S., Dolganov, G., Boushey, H., Avila, P., & Wu, R. (2006). Rhinovirus induces airway epithelial gene expression through double-stranded RNA and IFN-dependent pathways. American Journal of Respiratory Cell and Molecular Biology, 34(2), 192-203. https://doi.org/10.1165/rcmb.2004-0417OC