HERPES-SIMPLEX VIRUS GLYCOPROTEIN-K PROMOTES EGRESS OF VIRUS-PARTICLES

Herpes simplex virus (HSV) glycoprotein K (gK) is thought to be intima tely involved in the process by which infected cells fuse because HSV syncytial mutations frequently alter the gK (UL53) gene. Previously, w e characterized gK produced in cells infected with wild-type HSV or sy ncytial HSV mutants and found that the glycoprotein was localized to n uclear and endoplasmic reticulum membranes and did not reach the cell surface (L. Hutchinson, C. Poop, and D. C. Johnson, J. Virol. 69:4556- 4563, 1995). In this study, we have characterized a mutant HSV type 1, denoted F-gK beta, in which a lacZ gene cassette was inserted into th e gK coding sequences. Since gK was found to be essential for virus re plication, F-gK beta was propagated on complementing cells which can e xpress gK. F-gK beta produced normal plaques bounded by nonfused cells when plated on complementing cells, although syncytia were observed w hen the cells produced smaller amounts of gK. In contrast, F-gK beta p roduced only microscopic plaques on Vero cells and normal human fibrob lasts (which do not express gK) and these plaques were reduced by 10(2 ) to 10(6) in number. Further, large numbers of nonenveloped capsids a ccumulated in the cytoplasm of F-gK beta-infected Vero cells, virus pa rticles did not reach the cell surface, and the few enveloped particle s that were produced exhibited a reduced capacity to enter cells and i nitiate an infection of complementing cells. Overexpression of gK in H SV-infected cells also caused defects in virus egress, although partic les accumulated in the perinuclear space and large multilamellar membr anous structures juxtaposed with the nuclear envelope were observed. T ogether, these results demonstrate that gK regulates or facilitates eg ress of HSV from cells. How this property is connected to cell fusion is not clear. In this regard, gK may alter cell surface transport of v iral particles or other viral components directly involved in the fusi on process.