Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells.
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 beta1 or alpha5beta1 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.
Tugizov
Sharof M
SM
Department of Stomatology, School of Dentistry, University of California San Francisco, San Francisco, California, USA. tugizov@itsa.ucsf.edu
Berline
Jennifer W
JW
Palefsky
Joel M
JM
D000328:Adult; D000595:Amino Acid Sequence; D016764:Cell Polarity; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009305:Nasopharynx / Q000166:cytology / Q000821:virology*; D017464:Receptors, Complement 3d / Q000378:metabolism; D014059:Tongue / Q000166:cytology / Q000821:virology*; D014407:Tumor Cells, Cultured; D014764:Viral Proteins; D014771:Virion / Q000378:metabolism
C109482:BMRF-2 protein, Human herpesvirus 4; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D017464:Receptors, Complement 3d; D014764:Viral Proteins