Respiratory syncytial virus infection prolongs methacholine-induced airway hyperresponsiveness in ovalbumin-sensitized mice

J Med Virol. 1999 Feb;57(2):186-92. doi: 10.1002/(sici)1096-9071(199902)57:2<186::aid-jmv17>;2-q.


Severe respiratory syncytial virus (RSV)-induced disease is associated with childhood asthma and atopy. We combined models of allergen sensitization and RSV infection to begin exploring the immunologic interactions between allergic and virus-induced airway inflammation and its impact on airway hypersensitivity. Airway resistance was measured after methacholine challenge in tracheally intubated mice by whole body plethysmography. Lung inflammation was assessed by bronchoalveolar lavage (BAL) and histopathology. RSV infection alone did not cause significant airway hyperresponsiveness (AHR) to methacholine. Ovalbumin (OVA)-induced AHR lasted only a few days past the discontinuance of OVA aerosol in mice that were ovalbumin sensitized and mock infected. In contrast, OVA-sensitized mice infected with RSV during the OVA aerosol treatments (OVA/RSV) had AHR for more than 2 weeks after infection. However, 2 weeks after either RSV or mock infection, OVA/RSV mice had significantly more lymphocytes found during BAL than OVA mice, whereas the OVA and OVA/RSV groups had the same number of eosinophils. Histopathologic analysis confirmed an increased inflammation in the lungs of OVA/RSV mice compared with OVA mice. In addition, OVA/RSV mice had a more widespread distribution of mucus in their airways with increased amounts of intraluminal mucus pools compared with the other groups. Thus, prolonged AHR in RSV-infected mice during ovalbumin-sensitization correlates with increased numbers of lymphocytes in BAL fluid, increased lung inflammation, and mucus deposition in the airways, but not with airway eosinophilia. A further understanding of the immunologic consequences of combined allergic and virus-induced airway inflammation will impact the management of diseases associated with airway hyperreactivity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Weight / immunology
  • Bronchial Provocation Tests
  • Eosinophils / immunology
  • Female
  • Inflammation / immunology
  • Lung / drug effects
  • Lung / immunology
  • Lung / pathology
  • Lymphocytes / immunology
  • Macrophages / immunology
  • Methacholine Chloride / immunology*
  • Methacholine Chloride / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology*
  • Ovalbumin / pharmacology
  • Respiratory Hypersensitivity / chemically induced
  • Respiratory Hypersensitivity / immunology*
  • Respiratory Hypersensitivity / virology*
  • Respiratory Syncytial Virus Infections / immunology*
  • Specific Pathogen-Free Organisms
  • Time Factors
  • Viral Plaque Assay


  • Methacholine Chloride
  • Ovalbumin