title: A chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections.
abstract: BACKGROUND
  During respiratory viral infections host injury occurs due in part to inappropriate host responses. In this study we sought to uncover the host transcriptional responses underlying differences between high- and low-pathogenic infections.
  
  
  RESULTS
  From a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS coronavirus, we used meta-analysis to derive multiple gene expression signatures. We compared these signatures by their capacity to segregate biological conditions by pathogenicity and predict pathogenicity in a test data set. The highest-performing signature was expressed as a continuum in low-, medium-, and high-pathogenicity samples, suggesting a direct, analog relationship between expression and pathogenicity. This signature comprised 57 genes including a subnetwork of chemokines, implicating dysregulated cell recruitment in injury.
  
  
  CONCLUSIONS
  Highly pathogenic viruses elicit expression of many of the same key genes as lower pathogenic viruses but to a higher degree. This increased degree of expression may result in the uncontrolled co-localization of inflammatory cell types and lead to irreversible host damage.
authors.affiliation: Department of Microbiology, University of Washington, Seattle WA, USA.
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Chang
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tchitchek
authors.forename: Debashis
authors.initials: D
authors.lastname: Ghosh
authors.forename: Arndt
authors.initials: A
authors.lastname: Benecke
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
mesh_terms: D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000821:virology*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D018925:Chemokines