HERPES-SIMPLEX VIRUS GLYCOPROTEIN-K IS KNOWN TO INFLUENCE FUSION OF INFECTED-CELLS, YET IS NOT ON THE CELL-SURFACE

Syncytial mutants of herpes simplex virus (HSV) cause extensive fusion of cultured cells, whereas wild-type HSV primarily causes cell roundi ng and aggregation, A large fraction of syncytial viruses contain muta tions in the UL53 gene, which encodes glycoprotein K (gK). Previously, we demonstrated that wild-type and syncytial forms of gK are expresse d at similar levels and possess identical electrophoretic mobilities. Using immunofluorescence, we show that gK is not transported to the su rfaces of cells infected with either wild-type or syncytial HSV. Inste ad, gK accumulates in the perinuclear and nuclear membranes of cells. This finding is in contrast to the behavior of all other HSV glycoprot eins described to date, which reach the cell surface. When gK aas expr essed in the absence of other HSV proteins, using a recombinant adenov irus vector, a similar perinuclear and nuclear pattern was observed. I n addition, gK remained sensitive to endoglycosidase H, consistent wit h the hypothesis that gK does not reach the Golgi apparatus and is ret ained in the endoplasmic reticulum and nuclear envelope. Therefore, al though gK mutations promote fusion between the surface membranes of HS V-infected cells, the glycoprotein does not reach the plasma membrane and, thus, must influence fusion indirectly.