Herpes Simplex Virus (HSV) Glycoproteins B and K Inhibit Cell Fusion Induced by HSV Syncytial Mutants
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abstract
Herpes simplex virus type 1 (HSV-1) glycoproteins K and B (gK and gB) are intimately involved in virus-induced fusion of cells. Certain mutations in the UL27 (gB) and UL53 (gK) genes confer a syncytial (syn) phenotype characterized by extensive fusion of infected cells and giving rise to multinucleated cells. We have used HSV-1 syn mutants in conjunction with transfected cells or adenovirus vectors to overexpress wild-type gK or gB, in order to study the role of these proteins in virus-induced membrane fusion. Transient expression of wild-type gK inhibited fusion induced by HSV-1 encoding a mutant form of gK (syn gK) but not by viruses encoding a mutant form of gB (syn gB). Stably transformed cells expressing relatively high levels of gK suppressed cell fusion induced by HSV-1 mutants with lesions in the gK gene but not an HSV-1 with a syn mutation in the gB gene. In addition, there were marked reductions in the plaquing efficiencies and yields of HSV-1 on these cell lines. Cell fusion caused by HSV-1 syn20, a mutant encoding syn gK, was suppressed when cells were coinfected with an Ad vector, AdgK, which expresses wild-type gK. AdgK did not suppress fusion induced by HSV-1 KTTS.1, which expresses syn gB. Conversely, cells coinfected with AdgB, an Ad vector expressing a wild-type form of gB and HSV-1 KTTS.1 (syn gB) were not fused, whereas cells coinfected with AdgB and HSV-1 syn20 (syn gK) were fused. Expression of a number of other HSV-1 glycoproteins using Ad vectors did not reduce membrane fusion induced by syn gK or syn gB. Together, these results support models in which gK and gB participate directly in the fusion of HSV-infected cells. Mutant forms of gB and gK apparently disregulate the fusion process, whereas wild-type forms of gB and gK can act to suppress membrane fusion induced by their mutant counterparts.
