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Severe Acute Respiratory Syndrome Coronavirus Infection of Human Ciliated Airway Epithelia: Role of Ciliated Cells in Viral Spread in the Conducting Airways of the Lungs
Open accessAbstract
Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower respiratory tract infection in humans, and in vitro models of the lung are needed to elucidate cellular targets and the consequences of viral infection. The SARS-CoV receptor, human angiotensin 1-converting enzyme 2 (hACE2), was detected in ciliated airway epithelial cells of human airway tissues derived from nasal or tracheobronchial regions, suggesting that SARS-CoV may infect the proximal airways. To assess infectivity in an in vitro model of human ciliated airway epithelia (HAE) derived from nasal and tracheobronchial airway regions, we generated recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF7a/7b) and insertion of the green fluorescent protein (GFP), resulting in SARS-CoV GFP. SARS-CoV GFP replicated to titers similar to those of wild-type viruses in cell lines. SARS-CoV specifically infected HAE via the apical surface and replicated to titers of 10 7 PFU/ml by 48 h postinfection. Polyclonal antisera directed against hACE2 blocked virus infection and replication, suggesting that hACE2 is the primary receptor for SARS-CoV infection of HAE. SARS-CoV structural proteins and virions localized to ciliated epithelial cells. Infection was highly cytolytic, as infected ciliated cells were necrotic and shed over time onto the luminal surface of the epithelium. SARS-CoV GFP also replicated to a lesser extent in ciliated cell cultures derived from hamster or rhesus monkey airways. Efficient SARS-CoV infection of ciliated cells in HAE provides a useful in vitro model of human lung origin to study characteristics of SARS-CoV replication and pathogenesis.
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Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus
Li, W., Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) · Nature · doi:10.1038/nature02145 · Cited by 5,923
Identification of a novel coronavirus in patients with severe acute respiratory syndrome
Drosten, C., Günther, S., Preiser, W., van der Werf, S., Brodt, H.-R., Becker, S., Rabenau, H., Panning, M., Kolesnikova, L., Fouchier, R. A. M., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030747 · Cited by 4,574
A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., et al. (2005) · Nature Medicine · doi:10.1038/nm1267 · Cited by 3,445
Angiotensin-converting enzyme 2 protects from severe acute lung failure
Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, T., Leong-Poi, H., et al. (2005) · Nature · doi:10.1038/nature03712 · Cited by 2,453
Zhang, L., Bukreyev, A., Thompson, C. I., Watson, B., Peeples, M. E., Collins, P. L., & Pickles, R. J. (2005) · Journal of Virology · doi:10.1128/jvi.79.2.1113-1124.2005 · Cited by 302
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Self-citationLethal Infection of K18- hACE2 Mice Infected with Severe Acute Respiratory Syndrome Coronavirus
McCray, P. B., Pewe, L., Wohlford-Lenane, C., Hickey, M., Manzel, L., Shi, L., Netland, J., Jia, H. P., Halabi, C., Sigmund, C. D., et al. (2007) · Journal of Virology · doi:10.1128/jvi.02012-06 · Cited by 1,010
Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection
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An Infectious cDNA Clone of SARS-CoV-2
Xie, X., Muruato, A., Lokugamage, K. G., Narayanan, K., Zhang, X., Zou, J., Liu, J., Schindewolf, C., Bopp, N. E., Aguilar, P. V., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.04.004 · Cited by 647
Kreutz, R., Algharably, E. A. E.-H., Azizi, M., Dobrowolski, P., Guzik, T., Januszewicz, A., Persu, A., Prejbisz, A., Riemer, T. G., Wang, J.-G., et al. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa097 · Cited by 357
Metadata
- Authors
- Sims, A. C., Baric, R. S., Yount, B., Burkett, S. E., Collins, P. L., & Pickles, R. J.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2005-12-15
- Volume
- 79
- Issue
- 24
- Pages
- 15511-15524
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2043191762
- Cited by
- 349
- References
- 5
- FWCI
- 6.60
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Severe Acute Respiratory Syndrome Coronavirus Infection of Human Ciliated Airway Epithelia: Role of Ciliated Cells in Viral Spread in the Conducting Airways of the Lungs. https://app.cochat.ai/papers/10.1128/jvi.79.24.15511-15524.2005
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- Sims, A. C., Baric, R. S., Yount, B., Burkett, S. E., Collins, P. L., & Pickles, R. J. (2005). Severe Acute Respiratory Syndrome Coronavirus Infection of Human Ciliated Airway Epithelia: Role of Ciliated Cells in Viral Spread in the Conducting Airways of the Lungs. Journal of Virology. https://doi.org/10.1128/jvi.79.24.15511-15524.2005
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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