title: Herpes simplex virus gE/gI expressed in epithelial cells interferes with cell-to-cell spread.
abstract: The herpes simplex virus (HSV) glycoprotein heterodimer gE/gI plays an important role in virus cell-to-cell spread in epithelial and neuronal tissues. In an analogous fashion, gE/gI promotes virus spread between certain cell types in culture, e.g., keratinocytes and epithelial cells, cells that are polarized or that form extensive cell junctions. One mechanism by which gE/gI facilitates cell-to-cell spread involves selective sorting of nascent virions to cell junctions, a process that requires the cytoplasmic domain of gE. However, the large extracellular domains of gE/gI also appear to be involved in cell-to-cell spread. Here, we show that coexpression of a truncated form of gE and gI in a human keratinocyte line, HaCaT cells, decreased the spread of HSV between cells. This truncated gE/gI was found extensively at cell junctions. Expression of wild-type gE/gI that accumulates at intracellular sites, in the trans-Golgi network, did not reduce cell-to-cell spread. There was no obvious reduction in production of infectious HSV in cells expressing gE/gI, and virus particles accumulated at cell junctions, not at intracellular sites. Expression of HSV gD, which is known to bind virus receptors, also blocked cell-to-cell spread. Therefore, like gD, gE/gI appears to be able to interact with cellular components of cell junctions, gE/gI receptors which can promote HSV cell-to-cell spread.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health Sciences University, Portland, OR 97239, USA.
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Collins
authors.forename: David C
authors.initials: DC
authors.lastname: Johnson
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology*; D005822:Genetic Vectors; D006801:Humans; D007365:Intercellular Junctions / Q000821:virology*; D015603:Keratinocytes / Q000821:virology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018139:Simplexvirus / Q000472:pathogenicity / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D010948:Viral Plaque Assay; D014779:Virus Replication
chemical_list: D014759:Viral Envelope Proteins; C044768:glycoprotein E, herpes simplex virus type 1; C064959:glycoprotein I, herpes simplex virus type 1