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J. Virol. doi:10.1128/JVI.00601-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Vaccinia Virus Entry, Exit, and Interaction with Differentiated Human Airway Epithelia

Departments of Internal Medicine; and Physiology and Biophysics, Howard Hughes Medical Institute; Roy J. and Lucille A. Carver College of Medicine, University of Iowa Iowa City, Iowa 52242

^* To whom correspondence should be addressed. Email: michael-welsh{at}uiowa.edu.

	Abstract

Variola virus, the causative agent of smallpox, enters and exits the host via the respiratory route. To better understand the pathogenesis of poxvirus infection and its interaction with respiratory epithelia, we used vaccinia virus and examined its interaction with primary cultures of well-differentiated human airway epithelia. We found that vaccinia virus preferentially infected the epithelia through the basolateral membrane and released viral progeny across the apical membrane. Despite infection and virus production, epithelia retained tight junctions, transepithelial electrical conductance, and a steep transepithelial concentration gradient of virus, indicating integrity of the epithelial barrier. In fact, during the first four days of infection, epithelial height and cell number increased. These morphologic changes and maintenance of epithelial integrity required vaccinia growth factor (VGF) which was released basolaterally where it activated erbB1 receptors. These data suggest a complex interaction between the virus and differentiated airway epithelia; the virus preferentially enters the cells basolaterally, exits apically, and maintains epithelial integrity by stimulating growth factor receptors.