Enhanced virulence, airway inflammation and impaired lung function induced by respiratory syncytial virus deficient in secreted G protein.
BACKGROUND
Respiratory syncytial virus (RSV) infection can cause bronchial hyperresponsiveness and asthma exacerbations. In mice it results in airway inflammation and airway hyperresponsiveness. Since viral factors influencing these responses are not well defined, a study was undertaken to investigate the role of secreted G protein of human RSV in determining virulence, inflammatory responses, and changes in lung function.


METHODS
BALB/c mice were infected with a spontaneous mutant of RSV deficient in secreted G protein (RSV-DeltasG) or with wild type RSV (RSV-WT). Viral titres, numbers of pulmonary inflammatory cells, and concentrations of interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 in bronchoalveolar lavage (BAL) fluid were determined. Airway function was assessed at baseline and following methacholine provocation using barometric whole body plethysmography.


RESULTS
Following infection with RSV-DeltasG, viral titres were increased 50-fold compared with RSV-WT. Influx of eosinophils and macrophages to the lung and concentrations of IFN-gamma and IL-10 in BAL fluid were also significantly higher following infection with RSV-DeltasG. Airway function, both at baseline and after methacholine provocation, was significantly decreased following infection with RSV-DeltasG compared with RSV-WT.


CONCLUSIONS
Secreted G protein is likely to be a regulatory factor in RSV infection limiting infectivity of the virus, inflammatory responses in the lungs, and reduction in lung function.
Schwarze
J
J
Children's Clinic, St Josef-Hospital, 44791 Bochum, Germany. j.schwarze@ic.ac.uk
Schauer
U
U
D000818:Animals; D001991:Bronchitis / Q000503:physiopathology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency*; D008168:Lung / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018357:Respiratory Syncytial Virus Infections / Q000503:physiopathology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*
D016207:Cytokines; D019204:GTP-Binding Proteins