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Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells

Nature Medicine volume 9, pages 307–314 (2003)Cite this article

An Erratum to this article was published on 01 April 2003

A Corrigendum to this article was published on 01 April 2003

Abstract

Epstein-Barr virus (EBV) initially enters the body through the oropharyngeal mucosa and subsequently infects B lymphocytes through their CD21 (CR2) complement receptor. Mechanisms of EBV entry into and release from epithelial cells are poorly understood. To study EBV infection in mucosal oropharyngeal epithelial cells, we established human polarized tongue and pharyngeal epithelial cells in culture. We show that EBV enters these cells through three CD21-independent pathways: (i) by direct cell-to-cell contact of apical cell membranes with EBV-infected lymphocytes; (ii) by entry of cell-free virions through basolateral membranes, mediated in part through an interaction between b1 or α5β1 integrins and the EBV BMRF-2 protein; and (iii) after initial infection, by virus spread directly across lateral membranes to adjacent epithelial cells. Release of progeny virions from polarized cells occurs from both their apical and basolateral membranes. These data indicate that multiple approaches to prevention of epithelial infection with EBV will be necessary.

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Figure 1: Development of oropharyngeal epithelial cell polarity in vitro.
Figure 2: EBV attachment to polarized oropharyngeal epithelial cells.
Figure 3: EBV entry into polarized oropharyngeal epithelial cells.
Figure 4: Role of cell surface integrins in EBV infection of oropharyngeal epithelial cells.
Figure 5: Cell-to-cell spread of EBV across lateral membranes of Detroitsort cells.

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Acknowledgements

We thank E. Lennette for sera from nasopharyngeal carcinoma patients, V. Petersen for electron microscopy and P. Dazin for cell sorting assays. This project was supported by US National Institutes of Health grant P01 DE07946 and funds provided by the Division of Research Resources 5 M01-RR-00079, US Public Health Service.

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Authors and Affiliations

  1. Department of Stomatology, School of Dentistry, University of California San Francisco, San Francisco, California, USA

    Sharof M. Tugizov, Jennifer W. Berline & Joel M. Palefsky

  2. Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, California, USA

    Joel M. Palefsky

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Correspondence to Sharof M. Tugizov or Joel M. Palefsky.

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Tugizov, S., Berline, J. & Palefsky, J. Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells. Nat Med 9, 307–314 (2003). https://doi.org/10.1038/nm830

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