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 protein that can serve as coreceptor for herpes simplex virus type 1 (HSV-1) entry, herpesvirus entry mediator (previously designated HVEM but renamed HveA), also mediates HSV-1-induced cell cell fusion. We found that transfection of DNA from KOS 804, a previously described HSV-1 syncytial (Syn) strain whose SS?1 mutation was mapped to an amino acid substitution in gK, induced numerous large syncytia on HveA expressing Chinese hamster ovary cells (CHO-HVEM12) but not on control cells (CHO-CS). Antibodies specific for go as well as for HveA were effective inhibitors of KOS-804-induced fusion, consistent with previously described direct interactions between go and HveA. Since mutations in go determine the ability of HSV-1 to utilize HveA for entry, we examined whether the form of virally expressed go also influenced the ability of HveA to mediate fusion. We produced a recombinant virus carrying the KOS-804 Syn mutation and the KOS-Rid1 go mutation, which significantly reduces 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 mediates cell-cell fusion as well as viral entry and both activities of HveA are contingent upon the form of go expressed by the virus.