Effects of paramyxoviral infection on airway epithelial cell Foxj1 expression, ciliogenesis, and mucociliary function

To elucidate molecular mechanisms underlying the association between respir atory viral infection and predisposition to subsequent bacterial infection, we used in vivo and in vitro models and human samples to characterize resp iratory virus-induced changes in airway epithelial cell morphology, gene ex pression, and mucociliary function. Mouse paramyxoviral bronchitis resulted in airway epithelial cell infection and a distinct pattern of epithelial c ell morphology changes and altered expression of the differentiation marker s beta -tubulin-IV, Clara cell secretory protein, and Foxj1. Furthermore, c hanges in gene expression were recapitulated using an in vitro epithelial c ell culture system and progressed independent of the host inflammatory resp onse. Restoration of mature airway epithelium occurred in a pattern similar to epithelial cell differentiation and ciliogenesis in embryonic lung deve lopment characterized by sequential proliferation of undifferentiated cells , basal body production, Foxj1 expression, and beta -tubulin-IV expression. The effects of virus-induced alterations in morphology and gene expression on epithelial cell function were illustrated by decreased airway mucocilia ry velocity and impaired bacterial clearance. Similar changes in epithelial cell Foxj1 expression were also observed in human paramyxoviral respirator y infection. Taken together, these model systems of paramyxoviral respirato ry infection mimic human pathology and identify epithelial cell Foxj1 expre ssion as an early marker of epithelial cell differentiation, recovery, and function.