title: HveA (herpesvirus entry mediator A), a coreceptor for herpes simplex virus entry, also participates in virus-induced cell fusion.
abstract: 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 Syn 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-C8). Antibodies specific for gD as well as for HveA were effective inhibitors of KOS-804-induced fusion, consistent with previously described direct interactions between gD and HveA. Since mutations in gD determine the ability of HSV-1 to utilize HveA for entry, we examined whether the form of virally expressed gD also influenced the ability of HveA to mediate fusion. We produced a recombinant virus carrying the KOS-804 Syn mutation and the KOS-Rid1 gD 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 gD expressed by the virus.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
authors.forename: T
authors.initials: T
authors.lastname: Terry-Allison
authors.forename: R I
authors.initials: RI
authors.lastname: Montgomery
authors.forename: J C
authors.initials: JC
authors.lastname: Whitbeck
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.forename: G H
authors.initials: GH
authors.lastname: Cohen
authors.forename: R J
authors.initials: RJ
authors.lastname: Eisenberg
authors.forename: P G
authors.initials: PG
authors.lastname: Spear
mesh_terms: D000818:Animals; D016466:CHO Cells; D002459:Cell Fusion; D002522:Chlorocebus aethiops; D006224:Cricetinae; D018259:Herpesvirus 1, Human / Q000502:physiology*; D009154:Mutation; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000502:physiology*; D014709:Vero Cells
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human