Effects of respiratory syncytial virus persistence on airway responsiveness and inflammation in guinea-pigs

Recurrent wheezing and asthma often develop after acute respiratory syncyti al virus (RSV) bronchiolitis, but the mechanisms of these sequelae are poor ly understood. Using a guinea-pig model of human RSV Lung infection, the ef fects of long-term viral persistence on three hallmarks of asthma: nonspeci fic airway responsiveness, airway inflammation and airway remodelling were examined. Guinea-pigs were studied 100 days after intranasal instillation of either h uman RSV or uninfected vehicle, using: 1) acetylcholine challenge to test f or airway hyperresponsiveness (AHR); 2) lung histology to quantify the numb ers of airway eosinophils and metachromatic cells (mast cells/basophils); 3 ) airway morphometry of the areas of the airway subepithelial connective ti ssue, smooth muscle and adventitia, to test for airway remodelling; and 4) immunohistochemistry to identify lung cells containing RSV antigens. The RSV-inoculated group had significantly elevated AHR and airway eosinoph ils compared to uninfected control animals (p<0.05). There were no signific ant differences between the two groups in terms of numbers of airway metach romatic cells, or the areas of subepithelial connective tissue, smooth musc le or adventitia, Viral proteins were identified by immunohistochemistry wi thin several types of lung cells. In conclusion, long-term persistence of respiratory syncytial virus in the guinea-pig lung is associated with airway hyperresponsiveness and airway eo sinophilia, and these changes may be pertinent to the pathogenesis of postb ronchiolitis wheezing and asthma in children.