title: Differential responses to rhinovirus- and influenza-associated pulmonary exacerbations in patients with cystic fibrosis.
abstract: BACKGROUND
  The mechanism by which viruses cause exacerbations of chronic airway disease and the capacity of patients with cystic fibrosis (CF) to respond to viral infection are not precisely known.
  
  
  OBJECTIVE
  To determine the antiviral response to infection in patients with CF.
  
  
  METHODS
  Sputum was collected from patients with CF with respiratory exacerbation. Viruses were detected in multiplex polymerase chain reaction (PCR)-based assays. Gene expression of 84 antiviral response genes was measured, using a focused quantitative PCR gene array.
  
  
  RESULTS
  We examined 36 samples from 23 patients with respiratory exacerbation. Fourteen samples tested virus-positive and 22 virus-negative. When we compared exacerbations associated with rhinovirus (RV, n = 9) and influenza (n = 5) with virus-negative specimens, we found distinct patterns of antiviral gene expression. RV was associated with greater than twofold induction of five genes, including those encoding the monocyte-attracting chemokines CXCL10, CXCL11, and CXCL9. Influenza was associated with overexpression of 20 genes, including those encoding the cytokines tumor necrosis factor and IL-12; the kinases MEK, TBK-1, and STAT-1; the apoptosis proteins caspase-8 and caspase-10; the influenza double-stranded RNA receptor RIG-I and its downstream effector MAVS; and pyrin, an IFN-stimulated protein involved in influenza resistance.
  
  
  CONCLUSIONS
  We conclude that virus-induced exacerbations of CF are associated with immune responses tailored to specific infections. Influenza induced a more potent response consisting of inflammation, whereas RV infection had a pronounced effect on chemokine expression. As far as we are aware, this study is the first to compare specific responses to different viruses in live patients with chronic airway disease.
authors.affiliation: 1 Department of Pediatrics and Communicable Diseases.
authors.forename: Ixsy A
authors.initials: IA
authors.lastname: Ramirez
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Caverly
authors.forename: Lindsay L
authors.initials: LL
authors.lastname: Caverly
authors.forename: Linda M
authors.initials: LM
authors.lastname: Kalikin
authors.forename: Adam M
authors.initials: AM
authors.lastname: Goldsmith
authors.forename: Toby C
authors.initials: TC
authors.lastname: Lewis
authors.forename: David T
authors.initials: DT
authors.lastname: Burke
authors.forename: John J
authors.initials: JJ
authors.lastname: LiPuma
authors.forename: Uma S
authors.initials: US
authors.lastname: Sajjan
authors.forename: Marc B
authors.initials: MB
authors.lastname: Hershenson
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D053455:Caspase 10 / Q000235:genetics / Q000276:immunology; D053181:Caspase 8 / Q000235:genetics / Q000276:immunology; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology; D054371:Chemokine CXCL11 / Q000235:genetics / Q000276:immunology; D054370:Chemokine CXCL9 / Q000235:genetics / Q000276:immunology; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000276:immunology*; D020869:Gene Expression Profiling; D006801:Humans; D009980:Influenza A virus / Q000235:genetics; D007251:Influenza, Human / Q000150:complications / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D008297:Male; D010850:Picornaviridae Infections / Q000150:complications / Q000235:genetics / Q000276:immunology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology; D000071198:Pyrin; D011971:Receptors, Immunologic; D012189:Retrospective Studies; D012229:Rhinovirus / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology; D013183:Sputum / Q000821:virology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: C114753:CXCL10 protein, human; C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D011971:Receptors, Immunologic; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D048069:Tumor Necrosis Factors; D018664:Interleukin-12; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C505530:CASP8 protein, human; D053455:Caspase 10; D053181:Caspase 8; C506438:CASP10 protein, human; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases