Pathogenesis of bronchiolitis and pneumonia induced in neonatal and weanling rats by parainfluenza (Sendai) virus

Abstract

The objective of this research was to identify potential mechanisms that might account for the greater susceptibility of neonatal rats (5 days old) as compared with weanling rats (25 days old) to viral-induced lung injury. Sites of viral replication, the sequential development of bronchiolitis and pneumonia, and systemic humoral immune responses were compared between neonatal and weanling rats from 2 to 17 days after being inoculated intranasally with parainfluenza Type 1 (Sendai) virus. In both neonatal and weanling rats, viral antigen was demonstrated by immunoperoxidase technique and viral nucleocapsids, and budding virions were demonstrated by transmission electron microscopy in bronchiolar ciliated and nonciliated epithelial cells as early as 2 days after inoculation. Similar evidence of viral replication was also demonstrated in both ages of rats in alveolar Type I and Type II epithelial cells and in macrophages. Neither virus nor viral antigens was identified in endothelial cells or interstitial cells of interalveolar septa. Bronchiolitis was induced as early as 2 days after inoculation in both ages of rats and was characterized by necrosis, erosion, and hyperplasia of epithelial cells. Multifocal to locally extensive interstitial pneumonia centered on bronchioles, was characterized by alveolar epithelial cell damage and by infiltration of neutrophils, macrophages, and lymphocytes in alveolar septa and spaces and was observed as early as 2 days after inoculation in both age groups of rats. Interstitial pneumonia of maximal severity occurred in weanling rats at 5 days after inoculation, whereas maximal pneumonia of comparable severity occurred in neonatal rats at 8 days after inoculation. Epithelial repair and resolution of bronchiolitis and pneumonia were largely complete in both ages of rats by 17 days after inoculation. Virus was recovered from lung homogenates of neonatal and weanling rats as early as 2 days after inoculation. In weanling rats, infective virus could not be recovered from lung beyond 6 days after inoculation, whereas in neonatal rats virus could be recovered from lung as late as 10 days after inoculation. Viral persistence in neonatal rats was associated with a delayed onset of serum antibody to the virus, compared with weanling rats. The results indicate that the cellular sites of viral replication and the pattern of inflammatory reactions are closely comparable between neonatal and weanling rats inoculated with Sendai virus.(ABSTRACT TRUNCATED AT 400 WORDS)