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Journal of Virology, September 2007, p. 9891-9899, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00601-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Paola D. Vermeer,1 Julia McHugh,1 Tatiana Rokhlina,1 Daniel W. Vermeer,1 Joseph Zabner,1 and Michael J. Welsh1,2,3*

Departments of Internal Medicine,1 Physiology and Biophysics,2 Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 522423

Received 21 March 2007/ Accepted 15 June 2007

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 morphological changes and maintenance of epithelial integrity required vaccinia virus growth factor, which was released basolaterally, where it activated epidermal growth factor 1 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.


* Corresponding author. Mailing address: Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 500 EMRB, Iowa City, IA 52242. Phone: (319) 335-7619. Fax: (319) 335-7623. E-mail: michael-welsh{at}uiowa.edu

{triangledown} Published ahead of print on 20 June 2007.


Journal of Virology, September 2007, p. 9891-9899, Vol. 81, No. 18
0022-538X/07/$08.00+0     doi:10.1128/JVI.00601-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




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