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 vir ions, but how viral proteins interact with the host cell membranes that com prise intercellular junctions is not known. Madin-Darby canine kidney (MDCK ) cells were constructed to express the glycoproteins gE, gl, or gE/gI cons titutively 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 express ed alone or with gl. Although most VZV gE was intracellular, gE was also sh own to colocalize with the TJ protein ZO-1 with or without concomitant expr ession 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-gl and M DCK-gE/gI cells exhibited a similar pattern of early TER compared to MDCK c ells, although peak resistances were lower than those of gE alone. VZV gE e xpression altered F-actin organization and lipid distribution, but coexpres sion of gI modulated these effects. Two regions of the gE ectodomain, amino acids (aa) 278 to 355 and aa 467 to 498, although lacking Ca2+ binding mot ifs, exhibit similarities with corresponding regions of the cell adhesion m olecules, E-cadherin and desmocollin. These observations suggest that VZV g E and gE/gI may contribute to viral pathogenesis by facilitating epithelial cell-cell contacts.