title: Interferon regulatory factor 7 is a major hub connecting interferon-mediated responses in virus-induced asthma exacerbations in vivo.
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.
authors: Arizona Respiratory Center, University of Arizona, Tucson, Ariz, USA. anthonyb@ichr.uwa.edu.au
authors: Anthony
authors: A
authors: Bosco
authors: Samira
authors: S
authors: Ehteshami
authors: Sujatha
authors: S
authors: Panyala
authors: Fernando D
authors: FD
authors: Martinez
mesh_terms: D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D002648:Child; D016000:Cluster Analysis; D019295:Computational Biology; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D050839:Interferon Regulatory Factor-7 / Q000235:genetics* / Q000276:immunology; D007372:Interferons / Q000276:immunology*; D008297:Male; D055556:Nasal Lavage; D010850:Picornaviridae Infections / Q000150:complications*
chemical_list: D050839:Interferon Regulatory Factor-7; D007372:Interferons