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(American Journal of Pathology. 2001;159:2055-2069.)
© 2001 American Society for Investigative Pathology

Regular Article

Effects of Paramyxoviral Infection on Airway Epithelial Cell Foxj1 Expression, Ciliogenesis, and Mucociliary Function

Dwight C. Look^*, Michael J. Walter^*, Michael R. Williamson^*, Liyi Pang^*, Yingjian You^*, J. Nicholas Sreshta^*, Joyce E. Johnson, Dani S. Zander and Steven L. Brody^*

From the Department of Internal Medicine,^*
Washington University School of Medicine, St. Louis, Missouri; the Department of Pathology,
Vanderbilt University, Nashville, Tennessee; and the Department of Pathology, Immunology, and Laboratory Medicine,
University of Florida College of Medicine, Gainesville, Florida

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

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