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Journal of Virology, January 2005, p. 1113-1124, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1113-1124.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Infection of Ciliated Cells by Human Parainfluenza Virus Type 3 in an In Vitro Model of Human Airway Epithelium

Liqun Zhang,1 Alexander Bukreyev,2 Catherine I. Thompson,1 Brandy Watson,2 Mark E. Peeples,3,4 Peter L. Collins,2 and Raymond J. Pickles1,5*

Cystic Fibrosis/Pulmonary Research and Treatment Center,1 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina,5 Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,2 Center for Vaccines and Immunity, Columbus Children's Research Institute,3 Department of Pediatrics, The Ohio State University, Columbus, Ohio4

Received 5 July 2004/ Accepted 2 August 2004

We constructed a human recombinant parainfluenza virus type 3 (rPIV3) that expresses enhanced green fluorescent protein (GFP) and used this virus, rgPIV3, to characterize PIV3 infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). The apical surface of HAE was highly susceptible to rgPIV3 infection, whereas only occasional cells were infected when virus was applied to the basolateral surface. Infection involved exclusively ciliated epithelial cells. There was little evidence of virus-mediated cytopathology and no spread of the virus beyond the ciliated cell types. Infection of ciliated cells by rgPIV3 was sensitive to a neuraminidase specific for {alpha}2-6-linked sialic acid residues, but not to a neuraminidase that cleaves {alpha}2-3- and {alpha}2-8-linked sialic acid residues. This provided evidence that rgPIV3 utilizes {alpha}2-6-linked sialic acid residues for initiating infection, a specificity also described for human influenza viruses. The PIV3 fusion (F) glycoprotein was trafficked exclusively to the apical surface of ciliated cells, which also was the site of release of progeny virus. F glycoprotein localized predominately to the membranes of the cilial shafts, suggesting that progeny viruses may bud from cilia per se. The polarized trafficking of F glycoprotein to the apical surface also likely restricts its interaction with neighboring cells and could account for the observed lack of cell-cell fusion. HAE derived from cystic fibrosis patients was not more susceptible to rgPIV3 infection but did exhibit limited spread of virus due to impaired movement of lumenal secretions due to compromised function of the cilia.

* Corresponding author. Mailing address: CF/Pulmonary Research and Treatment Center, 7021 Thurston Bowles, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248. Phone: (919) 966-7044. Fax: (919) 966-5178. E-mail: branston{at}med.unc.edu.

Journal of Virology, January 2005, p. 1113-1124, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1113-1124.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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