HVEA (HERPESVIRUS ENTRY MEDIATOR-A), A CORECEPTOR FOR HERPES-SIMPLEX VIRUS ENTRY, ALSO PARTICIPATES IN VIRUS-INDUCED CELL-FUSION

The purpose of this study was to determine whether a cell surface prot ein that can serve as coreceptor for herpes simplex virus type 1 (HSV- 1) entry, herpesvirus entry mediator (previously designated HVEM but r enamed HveA), also mediates HSV-1-induced cell cell fusion. We found t hat transfection of DNA from KOS 804, a previously described HSV-1 syn cytial (Syn) strain whose SS?1 mutation was mapped to an amino acid su bstitution in gK, induced numerous large syncytia on HveA expressing C hinese hamster ovary cells (CHO-HVEM12) but not on control cells (CHO- CS). Antibodies specific for go as well as for HveA were effective inh ibitors of KOS-804-induced fusion, consistent with previously describe d direct interactions between go and HveA. Since mutations in go deter mine the ability of HSV-1 to utilize HveA for entry, we examined wheth er the form of virally expressed go also influenced the ability of Hve A to mediate fusion. We produced a recombinant virus carrying the KOS- 804 Syn mutation and the KOS-Rid1 go mutation, which significantly red uces viral entry via HveA, and designated it KOS-SR1. KOS-SR1 DNA had a markedly reduced ability to induce syncytia on CHO-HVEM12 cells and a somewhat enhanced ability to induce syncytia on CHO-C8 cells. These results support previous findings concerning the relative abilities of KOS and KOS-Rid1 to infect CHO-HVEM12 and CHO-C8 cells. Thus, HveA me diates cell-cell fusion as well as viral entry and both activities of HveA are contingent upon the form of go expressed by the virus.