| Respiratory syncytial virus (RSV) is the most important cause of bronchiolitis in infants. Viral infection of the bronchiolar epithelium results in destruction of epithelial cells and mucus production, leading to plugs that block airways and cause breathing difficulty. Disease severity has been correlated with RSV genotype; however, the impact of strain differences remains unclear.;We hypothesized that the pathogenesis of RSV disease is strain specific and used low-passage clinical isolates to examine differences in the BALB/cJ mouse model. Infection with isolate A2001/2-20 (2-20) induced higher lung IL-13 levels, airway mucin expression, and airway dysfuction than the genetically related isolate A2001/3-12 (3-12). It was previously shown that the fusion (F) protein of a mucus-inducing strain, line 19, is a factor in RSV mucin induction. We hypothesized that the F protein of 2-20 plays a role in RSV-induced mucin expression. We generated a chimeric RSV harboring the F gene of 2-20 in the genetic background of the non-mucogenic A2 strain. A2-2-20F infection resulted in early airway necrotic cell debris and lung mucin production. We also observed more neutrophil infiltration in the lungs of A2-2-20F-infected mice compared to mock- and A2-infected mice. This data indicates that F is a factor in RSV 2-20-induced mucus expression.;Neutrophils are abundant in the lungs of infants with severe RSV disease. Thus, we hypothesized that they play a role in 2-20 pathogenesis. Anti-Ly6G antibody was used to deplete neutrophils in RSV-infected mice. We observed lower lung mucin expression, less TNF-a, and less IL-13-expressing CD4+ T cells in neutrophil-depleted, RSV-infected mice compared to controls. Our findings demonstrated a novel role of neutrophils in virus-induced mucin response.;This body of data suggests that viral strain differences play a role in RSV severity. Sequence differences within F resulted in increased fusion activity and subsequent epithelial damage, followed by a robust neutrophil response that mediated lung mucin expression. Elucidating factors in RSV-associated airway pathology may have implications for treatment of severe RSV disease. |
