A CELL-SURFACE PROTEIN WITH HERPESVIRUS ENTRY ACTIVITY (HVEB) CONFERSSUSCEPTIBILITY TO INFECTION BY MUTANTS OF HERPES-SIMPLEX VIRUS TYPE-1, HERPES-SIMPLEX VIRUS TYPE-2, AND PSEUDORABIES VIRUS

Certain mutant strains of herpes simplex virus type 1 (HSV-1) are unab le to infect cells in which entry is dependent on HVEM, the previously described herpesvirus entry mediator designated here as herpesvirus e ntry protein A (HveA). These mutant viruses can infect other cells whe re entry is apparently dependent on other co-receptors. The mutant vir us HSV-1(KOS)Rid1 was used to screen a human cDNA expression library f or ability of transfected plasmids to convert resistant Chinese hamste r ovary cells to susceptibility to virus entry. A plasmid expressing t he previously described poliovirus receptor-related protein 2 (Prr2) w as isolated on the basis of this activity. This protein, designated he re as HveB, was shown to mediate the entry of three mutant HSV-I strai ns that cannot use HVEM as co-receptor, but not wild-type HSV-I strain s. HveB also mediated the entry of HSV-2 and pseudorabies virus but no t bovine herpesvirus type 1. HveB was expressed in some human neuronal cell lines, fibroblastic cells, keratinocytes, and primary activated T lymphocytes. Antibodies specific for HveB blocked infection of HveB- expressing CHO cells and a human fibroblastic cell strain HEL299. Diff erences in ability of HSV-I and HSV-2 strains to use HveB for entry sh ould influence the types of cells that can be infected and thereby acc ount in part for serotype and strain differences in tissue tropism and pathogenicity. (C) 1998 Academic Press.