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 especially evident for cells that form extensive cell junctions, e.g., epithelial cells, fibroblasts, and neurons. Mutants lacking gE or gI are not compromised in their ability to enter cells as extracellular viruses. Therefore, gE-gI functions specifically in the movement of virus across cell-cell contacts and, as such, provides a molecular handle on this poorly understood process. We expressed gE-gI in human epithelial cells by using replication-defective adenovirus (Ad) vectors. gE-gI accumulated at lateral surfaces of the epithelial cells, colocalizing with the adherens junction protein beta-catenin but was not found on either 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. Similar localization of gE-gI to cell junctions was observed in HSV-infected epithelial cells. By contrast, HSV glycoprotein gD, expressed using a recombinant Ad vectors, was found primarily along the apical surfaces of cells, with little or no protein found on the basal or lateral surfaces. Expression of gE-gI without other HSV polypeptides did not cause redistribution of either ZO-1 or beta-catenin or alter tight-junction functions. Together these results support a model in which gE-gI accumulates at sites of cell-cell contact by interacting with junctional components. We hypothesize that gE-gI mediates transfer of HSV across cell junctions by virtue of these interactions with cell junction components.
Department of Biology, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
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Dingwell
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Johnson
D000260:Adenoviruses, Human / Q000235:genetics; D004847:Epithelial Cells / Q000821:virology; D015870:Gene Expression; D005814:Genes, Viral; D005822:Genetic Vectors; D006561:Herpes Simplex / Q000209:etiology / Q000821:virology; D006801:Humans; D007365:Intercellular Junctions / Q000821:virology*; D008954:Models, Biological; D018139:Simplexvirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D012995:Solubility; D013347:Subcellular Fractions / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1; C064959:glycoprotein I, herpes simplex virus type 1