Respiratory syncytial virus infection in the absence of STAT 1 results in airway dysfunction, airway mucus, and augmented IL-17 levels

J Allergy Clin Immunol. 2005 Sep;116(3):550-7. doi: 10.1016/j.jaci.2005.03.051.


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.

Conclusion: These results show that STAT 1 has an important regulatory role in RSV-induced alteration of airway function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Bronchial Hyperreactivity / etiology
  • Bronchoalveolar Lavage Fluid / cytology
  • Chloride Channels / biosynthesis
  • DNA-Binding Proteins / deficiency*
  • Eosinophilia / etiology
  • Female
  • Immunohistochemistry
  • Interleukin-17 / biosynthesis*
  • Lung / physiopathology
  • Lung / virology*
  • Male
  • Mice
  • Mice, Knockout
  • Mucin 5AC
  • Mucins / biosynthesis
  • Mucoproteins / biosynthesis
  • Mucus / metabolism*
  • Respiratory Function Tests
  • Respiratory Syncytial Virus Infections / physiopathology*
  • Respiratory Syncytial Virus, Human
  • STAT1 Transcription Factor
  • Trans-Activators / deficiency*


  • Chloride Channels
  • Clca3a1 protein, mouse
  • DNA-Binding Proteins
  • Interleukin-17
  • Muc5ac protein, mouse
  • Mucin 5AC
  • Mucins
  • Mucoproteins
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Trans-Activators