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Journal of Virology, August 2005, p. 9470-9479, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9470-9479.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Apical Entry and Release of Severe Acute Respiratory Syndrome-Associated Coronavirus in Polarized Calu-3 Lung Epithelial Cells

Chien-Te K. Tseng,1,2* Jennifer Tseng,2 Lucy Perrone,2 Melissa Worthy,1 Vsevolod Popov,2 and Clarence J. Peters1,2

Department of Microbiology and Immunology,1 Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-06092

Received 5 January 2005/ Accepted 14 April 2005

Severe acute respiratory syndrome (SARS), caused by a novel coronavirus (CoV) known as SARS-CoV, is a contagious and life-threatening respiratory illness with pneumocytes as its main target. A full understanding of how SARS-CoV would interact with lung epithelial cells will be vital for advancing our knowledge of SARS pathogenesis. However, an in vitro model of SARS-CoV infection using relevant lung epithelial cells is not yet available, making it difficult to dissect the pathogenesis of SARS-CoV in the lungs. Here, we report that SARS-CoV can productively infect human bronchial epithelial Calu-3 cells, causing cytopathic effects, a process reflective of its natural course of infection in the lungs. Indirect immunofluorescence studies revealed a preferential expression of angiotensin-converting enzyme 2 (ACE-2), the functional receptor of SARS-CoV, on the apical surface. Importantly, both ACE-2 and viral antigen appeared to preferentially colocalize at the apical domain of infected cells. In highly polarized Calu-3 cells grown on the membrane inserts, we found that cells exposed to virus through the apical rather than the basolateral surface showed high levels of viral replication. Progeny virus was released into the apical chamber at titers up to 5 logs higher than those recovered from the basolateral chambers of polarized cultures. Taken together, these results indicate that SARS-CoV almost exclusively entered and was released from the apical domain of polarized Calu-3 cells, which might provide important insight into the mechanism of transmission and pathogenesis of SARS-CoV.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, G-150 Keiller Building, Galveston, TX 77555-0609. Phone: (409) 772-0091. Fax: (409) 747-0762. E-mail: sktseng{at}utmb.edu.

Journal of Virology, August 2005, p. 9470-9479, Vol. 79, No. 15
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.15.9470-9479.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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