title: Herpes simplex virus glycoprotein K is known to influence fusion of infected cells, yet is not on the cell surface.
abstract: Syncytial mutants of herpes simplex virus (HSV) cause extensive fusion of cultured cells, whereas wild-type HSV primarily causes cell rounding and aggregation. A large fraction of syncytial viruses contain mutations in the UL53 gene, which encodes glycoprotein K (gK). Previously, we demonstrated that wild-type and syncytial forms of gK are expressed at similar levels and possess identical electrophoretic mobilities. Using immunofluorescence, we show that gK is not transported to the surfaces of cells infected with either wild-type or syncytial HSV. Instead, gK accumulates in the perinuclear and nuclear membranes of cells. This finding is in contrast to the behavior of all other HSV glycoproteins described to date, which reach the cell surface. When gK was expressed in the absence of other HSV proteins, using a recombinant adenovirus vector, a similar perinuclear and nuclear pattern was observed. In addition, gK remained sensitive to endoglycosidase H, consistent with the hypothesis that gK does not reach the Golgi apparatus and is retained in the endoplasmic reticulum and nuclear envelope. Therefore, although gK mutations promote fusion between the surface membranes of HSV-infected cells, the glycoprotein does not reach the plasma membrane and, thus, must influence fusion indirectly.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Hutchinson
authors.forename: C
authors.initials: C
authors.lastname: Roop-Beauchamp
authors.forename: D C
authors.initials: DC
authors.lastname: Johnson
mesh_terms: D000818:Animals; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D006596:Hexosaminidases / Q000494:pharmacology; D009685:Nuclear Envelope / Q000737:chemistry; D009844:Oligosaccharides / Q000378:metabolism; D018139:Simplexvirus / Q000502:physiology*; D014709:Vero Cells; D014764:Viral Proteins / Q000032:analysis / Q000502:physiology*
chemical_list: D009844:Oligosaccharides; C072448:UL53 protein, Human herpesvirus 1; D014764:Viral Proteins; D006596:Hexosaminidases