title: Respiratory syncytial virus infection in the absence of STAT 1 results in airway dysfunction, airway mucus, and augmented IL-17 levels.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is the leading infectious cause of respiratory failure and wheezing in infants and young children. Prematurity is the greatest risk factor for severe RSV-induced disease, and recent studies suggest that premature children have lower levels of the type I IFNs (alpha/beta), for which signal transducer and activator of transcription (STAT) 1 is a critical intracellular signaling molecule.
  
  
  OBJECTIVE
  We hypothesized that RSV infection in STAT 1 knockout (STAT 1 KO) mice would result in both increased airway resistance and airway hyperresponsiveness.
  
  
  METHODS
  Wild-type (WT) and STAT 1 KO mice on a BALB/c background were either RSV or mock infected. Phenotypic response to infection was assessed by means of plethysmography, immunohistochemistry, and lung cytokine measurement.
  
  
  RESULTS
  We found that STAT 1 KO mice infected with RSV (STAT 1 KO-RSV) had greater baseline lung resistance (P=.05) and airway responsiveness (P<.001) than mock-infected STAT 1 KO (STAT 1 KO-MOCK), RSV-infected wild type (WT-RSV), and mock-infected wild type (WT-MOCK) mice. In addition, the STAT 1 KO-RSV mice showed induction of mucus production and expression of gob-5 and Muc5ac, conditions not present in any of the other 3 groups. IL-17, a cytokine that regulates Muc5ac expression, was expressed in the lungs of the STAT 1 KO-RSV mice, whereas lung levels of IL-17 were undetectable in the remaining groups. Expression of the IL-23-specific p19 subunit was also increased in the STAT 1 KO-RSV mice but not in the WT-RSV mice.
  
  
  CONCLUSIONS
  These results show that STAT 1 has an important regulatory role in RSV-induced alteration of airway function.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2650, USA.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Joan E
authors.initials: JE
authors.lastname: Durbin
authors.forename: Weisong
authors.initials: W
authors.lastname: Zhou
authors.forename: Robert D
authors.initials: RD
authors.lastname: Collins
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Ho
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Dubin
authors.forename: James R
authors.initials: JR
authors.lastname: Sheller
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Jamye F
authors.initials: JF
authors.lastname: O'Neal
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Olson
authors.forename: Daphne
authors.initials: D
authors.lastname: Mitchell
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018118:Chloride Channels / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004802:Eosinophilia / Q000209:etiology; D005260:Female; D007150:Immunohistochemistry; D020381:Interleukin-17 / Q000096:biosynthesis*; D008168:Lung / Q000503:physiopathology / Q000821:virology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D055271:Mucin 5AC; D009077:Mucins / Q000096:biosynthesis; D009088:Mucoproteins / Q000096:biosynthesis; D009093:Mucus / Q000378:metabolism*; D012129:Respiratory Function Tests; D018357:Respiratory Syncytial Virus Infections / Q000503:physiopathology*; D018113:Respiratory Syncytial Virus, Human; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000172:deficiency*
chemical_list: D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D004268:DNA-Binding Proteins; D020381:Interleukin-17; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; D009088:Mucoproteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D015534:Trans-Activators