Glycoprotein E of varicella-zoster virus enhances cell-cell contact in polarized epithelial cells.
Varicella-zoster virus (VZV) infection involves the cell-cell spread of virions, but how viral proteins interact with the host cell membranes that comprise intercellular junctions is not known. Madin-Darby canine kidney (MDCK) cells were constructed to express the glycoproteins gE, gI, or gE/gI constitutively and were used to examine the effects of these VZV glycoproteins in polarized epithelial cells. At low cell density, VZV gE induced partial tight junction (TJ) formation under low-calcium conditions, whether expressed alone or with gI. Although most VZV gE was intracellular, gE was also shown to colocalize with the TJ protein ZO-1 with or without concomitant expression of gI. Freeze fracture electron microscopy revealed normal TJ strand morphology in gE-expressing MDCK cells. Functionally, the expression of gE was associated with a marked acceleration in the establishment of maximum transepithelial electrical resistance (TER) in MDCK-gE cells; MDCK-gI and MDCK-gE/gI cells exhibited a similar pattern of early TER compared to MDCK cells, although peak resistances were lower than those of gE alone. VZV gE expression altered F-actin organization and lipid distribution, but coexpression of gI modulated these effects. Two regions of the gE ectodomain, amino acids (aa) 278 to 355 and aa 467 to 498, although lacking Ca(2+) binding motifs, exhibit similarities with corresponding regions of the cell adhesion molecules, E-cadherin and desmocollin. These observations suggest that VZV gE and gE/gI may contribute to viral pathogenesis by facilitating epithelial cell-cell contacts.
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Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA. cmo@cmgm.stanford.edu
Schneeberger
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Arvin
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AM
D000199:Actins / Q000032:analysis; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000737:chemistry; D002450:Cell Communication; D002460:Cell Line; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000737:chemistry; D051187:Desmocollins; D051180:Desmoplakins; D004285:Dogs; D017097:Electric Impedance; D004847:Epithelial Cells / Q000502:physiology; D014645:Herpesvirus 3, Human / Q000502:physiology*; D008055:Lipids / Q000032:analysis; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D019108:Tight Junctions; D014759:Viral Envelope Proteins / Q000502:physiology*
D000199:Actins; D015820:Cadherins; D003598:Cytoskeletal Proteins; D051187:Desmocollins; D051180:Desmoplakins; D008055:Lipids; D014759:Viral Envelope Proteins; C056913:glycoprotein E, varicella-zoster virus