Persistence of respiratory syncytial virus (RSV) infection and development of RSV-specific IgG1 response in a guinea-pig model of acute bronchiolitis

Acute respiratory syncytial virus (RSV) bronchiolitis in children can result in sequelae of recurrent wheezing and asthma and production of RSV-specific immunoglobulin E (IgE), but the pathogenesis of these sequeleae is poorly understood. Guinea-pigs experimentally inoculated with human RSV show histological evidence of acute bronchiolitis and chronic persistence of viral antigens and genome in the lungs; whether this persistence is due to infectious replicating virus, and whether infected animals develop RSV-specific immunoglobulin G1 (IgG1) (the main class of antibody involved in guinea-pig allergic responses) is unknown. Guinea-pigs were inoculated intranasally with human RSV or with uninfected cell culture supernatant. At times ranging 1-60 days postinoculation, the viral titre in the lung was determined by immunoplaque assay (a method combining viral culture and immunocytochemistry). Serum titres of RSV-specific IgG1 antibodies were determined by enzyme-linked immunosorbent assay. Bronchiolar inflammation was assessed on coded lung sections, by using a semiquantitative, histological scoring system based on features of human acute bronchiolitis. Infectious RSV was cultured from the lungs of infected animals on all study days, with maximal viral replication observed on Day 3. RSV-specific IgG1 antibodies were detected in all RSV-inoculated animals from Day 7 onward, with the highest antibody titre measured on Day 28. RSV-inoculated guinea-pigs had maximal bronchiolar inflammation on Day 7, and had significantly increased polymorphonuclear cell infiltrates on Days 28 and 60. Respiratory syncytial virus chronically persists as infectious virus in the guinea-pig lung. Infected animals develop an anti-respiratory syncytial virus immunoglobulin G1 antibody response, histological evidence of acute bronchiolitis, and chronic airway inflammation. Persistent respiratory syncytial virus lung infection may be important in the pathogenesis of postbronchiolitis wheezing and asthma in children.

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