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 seq uelae is poorly understood. Guinea-pigs experimentally inoculated with human RSV show histological evidence of acute bronchiolitis and chron ic persistence of viral antigens and genome in the lungs; whether this persistence is due to infectious replicating virus, and whether infec ted animals develop RSV-specific immunoglobulin G1 (IgG1) (the main cl ass of antibody involved in guinea-pig allergic responses) is unknown. Guinea-pigs were inoculated intranasally with human RSV or with uninf ected tell culture supernatant. At times ranging 1-60 days postinocula tion, the viral titre in the lung was determined by immunoplaque assay (a method combining viral culture and immunocytochemistry). Serum tit res of RSV-specific IgG1 antibodies were determined by enzyme-linked i mmunosorbent assay. Bronchiolar inflammation was assessed on coded lun g sections, by using a semiquantitative, histological scoring system b ased on features of human acute bronchiolitis. Infectious RSV was cult ured from the lungs of infected animals on all study days, with maxima l viral replication observed on Day 3. RSV-specific IgG1 antibodies we re 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 i ncreased polymorphonuclear cell infiltrates on Days 28 and 60. Respira tory syncytial virus chronically persists as infectious virus in the g uineapig lung. Infected animals develop an anti-respiratory syncytial virus immunoglobulin G1 antibody response, histological evidence of ac ute bronchiolitis, and chronic airway inflammation. Persistent respira tory syncytial virus lung infection may be important in the pathogenes is of postbronchiolitis wheezing and asthma in children. (C)ERS Journa ls Ltd 1997.