Production of acute bronchiolitis in guinea-pigs by human respiratory syncytial virus

Abstract

Respiratory syncytial virus (RSV) is the most important cause of acute bronchiolitis in young children, and is implicated in the pathogenesis of paediatric asthma. The present studies were designed to develop a model of acute RSV bronchiolitis in young guinea-pigs, that could be used to study the mechanisms of the acute bronchiolitis and its sequelae. Anaesthetized, one month old guinea-pigs received either 4 x 10(3) plaque forming units of Long strain human RSV or uninfected cell culture medium intranasally. Bronchiolar inflammation was assessed 6 days (n = 10 RSV-inoculated; n = 10 controls) and 14 days (n = 10 RSV-inoculated; n = 9 controls) postinoculation using a semiquantitative histological scoring system. Viral replication within the lung was evaluated by culture, and the intrapulmonary distribution of viral antigens was evaluated by immunohistochemistry. The RSV-inoculated group showed histological evidence of acute bronchiolitis 6 days after inoculation, which subsided by Day 14. Replicating virus was cultured from the lungs of 9 out of 10 RSV-inoculated animals on Day 6, and 2 out of 10 animals on Day 14, with no growth from control animals. Viral antigens were identified primarily within airway epithelial cells on Day 6, and within alveolar macrophages on Day 14. Intranasal inoculation of human RSV into guinea-pigs provides a model of acute RSV bronchiolitis that may facilitate the study of both the pathogenesis of acute infection and the possible role of RSV in the subsequent development of nonspecific bronchial hyperresponsiveness in children.