Viral induction of a chronic asthma phenotype and genetic segregation from the acute response

J Clin Invest. 2002 Jul;110(2):165-75. doi: 10.1172/JCI14345.


Paramyxoviral infections cause most of the acute lower respiratory tract illness in infants and young children and predispose to the development of chronic wheezing, but the relationship between these short- and long-term viral effects are uncertain. Here we show that a single paramyxoviral infection of mice (C57BL6/J strain) not only produces acute bronchiolitis, but also triggers a chronic response with airway hyperreactivity and goblet cell hyperplasia lasting at least a year after complete viral clearance. During the acute response to virus, same-strain ICAM-1-null mice are protected from airway inflammation and hyperreactivity despite similar viral infection rates, but the chronic response proceeds despite ICAM-1 deficiency. Neither response is influenced by IFN-gamma deficiency, but the chronic response is at least partially prevented by glucocorticoid treatment. In contrast to viral infection, allergen challenge caused only short-term expression of asthma phenotypes. Thus, paramyxoviruses cause both acute airway inflammation/hyperreactivity and chronic airway remodeling/hyperreactivity phenotypes (the latter by a hit-and-run strategy, since viral effects persist after clearance). These two phenotypes can be segregated by their dependence on the ICAM-1 gene and so depend on distinct controls that appear critical for the development of lifelong airway diseases such as asthma.

Publication types

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

MeSH terms

  • Acute Disease
  • Allergens / administration & dosage
  • Animals
  • Asthma / etiology*
  • Asthma / genetics
  • Asthma / pathology
  • Bronchiolitis / complications
  • Child, Preschool
  • Chronic Disease
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Glucocorticoids / pharmacology
  • Humans
  • Infant
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Respiratory Hypersensitivity / etiology
  • Respirovirus Infections / complications*
  • Sendai virus / pathogenicity


  • Allergens
  • Glucocorticoids
  • Intercellular Adhesion Molecule-1
  • Dexamethasone