Respiratory syncytial virus infection in the absence of STAT1 results in airway dysfunction, airway mucus, and augmented IL-17 levels

Koichi Hashimoto, Joan E. Durbin, Weisong Zhou, Robert D. Collins, Samuel B. Ho, Jay K. Kolls, Patricia J. Dubin, James R. Sheller, Kasia Goleniewska, Jamye F. O'Neal, Sandra J. Olson, Daphne Mitchell, Barney S. Graham, R. Stokes Peebles

Research output: Contribution to journalArticlepeer-review

97 Scopus citations


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 (α/β), for which signal transducer and activator of transcription (STAT) 1 is a critical intracellular signaling molecule. Objective: We hypothesized that RSV infection in STAT1 knockout (STAT1 KO) mice would result in both increased airway resistance and airway hyperresponsiveness. Methods: Wild-type (WT) and STAT1 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 STAT1 KO mice infected with RSV (STAT1 KO-RSV) had greater baseline lung resistance (P = .05) and airway responsiveness (P < .001) than mock-infected STAT1 KO (STAT1 KO-MOCK), RSV-infected wild type (WT-RSV), and mock-infected wild type (WT-MOCK) mice. In addition, the STAT1 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 STAT1 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 STAT1 KO-RSV mice but not in the WT-RSV mice. Conclusion: These results show that STAT1 has an important regulatory role in RSV-induced alteration of airway function.

Original languageEnglish (US)
Pages (from-to)550-557
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number3
StatePublished - Sep 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


  • Cytokines
  • IL-17
  • IL-23
  • Inflammation
  • Mucus
  • Rodent
  • Viral


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