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Infection of Ciliated Cells by Human Parainfluenza Virus Type 3 in an In Vitro Model of Human Airway Epithelium
Open accessAbstract
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 α2-6-linked sialic acid residues, but not to a neuraminidase that cleaves α2-3- and α2-8-linked sialic acid residues. This provided evidence that rgPIV3 utilizes α2-6-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.
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“Type III IFNs possess antiviral properties similar to those of type I IFNs but appear to be expressed especially by epithelial cells and consequently exert host protection primarily at epithelial surfaces (8, 9, 335).”
From The airway epithelium: soldier in the fight against respiratory viruses (2011) · cites this paper as [335]
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Phillips, M. A., Lei, L., Kulhánková, K., Gingerich, M. C., Loza, L. I. M., Vu, A., He, B., Thornell, I. M., & McCray, P. B. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.102975 · Cited by 1
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Brunet, M. A., Lopes, L. J. S., Mansfield, N., Sardar, A., Marcink, T. C., Blank, P. S., Cotten, M. L., Moscona, A., Sodt, A. J., & Zimmerberg, J. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.07.757304
Use of microphysiological models to study human antiviral responses
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Metadata
- Authors
- Zhang, L., Bukreyev, A., Thompson, C. I., Watson, B., Peeples, M. E., Collins, P. L., & Pickles, R. J.
- Affiliations
- Cystic Fibrosis/Pulmonary Research and Treatment Center
- National Institutes of Health (US)
- Abigail Wexner Research Institute (US)
- University of North Carolina at Chapel Hill (US)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2005-01-15
- Volume
- 79
- Issue
- 2
- Pages
- 1113-1124
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC538579
- OpenAlex
- W2159953474
- Cited by
- 302
- References
- 50
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 19 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 19 · 2019: 17 · 2018: 12 · 2017: 9 · 2016: 11 · 2015: 9 · 2014: 16 · 2013: 12 · 2012: 15
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (P01HL051818, HL 66943-01, HL 51818-09)
- Topics
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Keywords
- parainfluenza virus type 3, ciliated epithelial cells, airway epithelium, neuraminidase sensitivity, cell-cell fusion, cystic fibrosis
- MeSH terms
- Bronchi, Cell Differentiation, Cells, Cultured, Cilia, Epithelial Cells, Heparan Sulfate, Heparitin Sulfate, Humans, Neuraminidase, Parainfluenza Virus 3, Human, Trachea, Viral Proteins, Virus Shedding, N-Acetylneuraminic Acid
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