Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo

Anthony Bosco, Samira Ehteshami, Sujatha Panyala, Fernando D. Martinez

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Background: Exacerbations are responsible for a substantial burden of morbidity and health care use in children with asthma. Most asthma exacerbations are triggered by viral infections; however, the underlying mechanisms have not been systematically investigated. Objective: The objective of this study was to elucidate the molecular networks that underpin virus-induced exacerbations in asthmatic children in vivo. Methods: We followed exacerbation-prone asthmatic children prospectively and profiled global patterns of gene expression in nasal lavage samples obtained during an acute, moderate, picornavirus-induced exacerbation and 7 to 14 days later. Coexpression network analysis and prior knowledge was used to reconstruct the underlying gene networks. Results: The data showed that an intricate modular program consisting of more than 1000 genes was upregulated during acute exacerbations in comparison with 7 to 14 days later. The modules were enriched for coherent cellular processes, including interferon-induced antiviral responses, innate pathogen sensing, response to wounding, small nucleolar RNAs, and the ubiquitin-proteosome and lysosome degradation pathways. Reconstruction of the wiring diagram of the modules revealed the presence of hyperconnected hub nodes, most notably interferon regulatory factor 7, which was identified as a major hub linking interferon-mediated antiviral responses. Conclusions: This study provides an integrated view of the inflammatory networks that are upregulated during virus-induced asthma exacerbations in vivo. A series of innate signaling hubs were identified that could be novel therapeutic targets for asthma attacks.

Original languageEnglish (US)
Pages (from-to)88-94
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume129
Issue number1
DOIs
StatePublished - Jan 1 2012

Keywords

  • Asthma
  • exacerbation
  • gene expression
  • gene networks
  • innate immunity
  • interferons
  • picornavirus
  • rhinovirus
  • systems biology

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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