Glycoprotein D homologs in herpes simplex virus type 1, pseudorabies virus, and bovine herpes virus type 1 bind directly to human HveC (nectin-1) with different affinities

Distinct subsets of human receptors for alphaherpesviruses mediate the entr y of herpes simplex virus (HSV), pseudorabies virus (PrV), or bovine herpes virus type 1 (BHV-1) into cells. Glycoprotein D (gD) is essential for rece ptor-mediated entry of all three viruses into cells. However, the go homolo gs of these viruses share only 22-33% amino acid identity. Several entry re ceptors for HSV have been identified. Two of these. HveA (HVEM) and HveC (n ectin-1), mediate entry of most HSV-1 and HSV-2 strains and are bound direc tly by HSV go. A third receptor, HveB (nectin-2), mediates entry of HSV-2 a nd only a limited number of HSV-1 strains. HveB and HveC can also serve as entry receptors for PrV, whereas only HveC can serve this function for BHV- 1. We show here that go from PrV and BHV-1 binds directly to the human rece ptors that mediate PrV and Bf(V-l entry We expressed soluble forms of PrV g o and BHV-1 go using recombinant baculoviruses and purified each protein. U sing ELISA, we detected direct binding of PrV go to HveB and HveC and direc t binding of BHV-1 go to HveC. Biosensor analysis revealed that PN go had a 10-fold higher affinity than HSV-1 go for human HveC. In contrast, the bin ding of BHV-1 go to HveC was weak. PrV go and HSV-1 go competed for binding to the V domain of HveC and both inhibited entry of the homologous and het erologous viruses. These data suggest that the two forms of go bind to a co mmon region on human HveC despite their low amino acid similarity. Based on affinities for human HveC, we predict a porcine HveC homolog may be import ant for PN infection in its natural host, whereas a BHV-1 infection in its natural host may be mediated by a receptor other than a bovine HveC homolog . (C) 2001 Academic Press.