THE HERPES-SIMPLEX VIRUS GE-GI COMPLEX FACILITATES CELL-TO-CELL SPREAD AND BINDS TO COMPONENTS OF CELL-JUNCTIONS

The herpes simplex virus (HSV) glycoprotein complex gE-gI mediates the spread of viruses between adjacent cells, and this property is especi ally evident for cells that form extensive cell junctions, e.g., epith elial cells, fibroblasts, and neurons. Mutants lacking gE or gI are no t compromised in their ability to enter cells as extracellular viruses . Therefore, gE-gI functions specifically in the movement of virus acr oss cell-cell contacts and, as such, provides a molecular handle on th is poorly understood process. We expressed gE-gI in human epithelial c ells by using replication-defective adenovirus (Ad) vectors. gE-gI acc umulated at lateral surfaces of the epithelial cells, colocalizing wit h the adherens junction protein beta-catenin but was not found on eith er the apical or basal plasma membranes and did not colocalize with ZO -1, a component of tight junctions. In subconfluent monolayers, gE-gI was found at cell junctions but was absent from those lateral surfaces not in contact with another cell, as was the case for beta-catenin, S imilar localization of gE-gI to cell junctions was observed in HSV-inf ected epithelial cells. By contrast, HSV glycoprotein go, expressed us ing a recombinant Ad vectors, was found primarily along the apical sur faces of cells, with little or no protein found on the basal or latera l surfaces. Expression of gE-gI without other HSV polypeptides did not cause redistribution of either ZO-1 or beta-catenin or alter tight-ju nction functions, Together these results support a model in which gE-g I accumulates at sites of cell-cell contact by interacting with juncti onal components, We hypothesize that gE-gI mediates transfer of HSV ac ross cell junctions by virtue of these interactions with cell junction components.