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

摘要

Distinct subsets of human receptors for alphaherpesviruses mediate the entry of herpes simplex virus (HSV), pseudorabies virus (PrV), or bovine herpes virus type 1 (BHV-1) into cells. Glycoprotein D (gD) is essential for receptor-mediated entry of all three viruses into cells. However, the go homologs of these viruses share only 22-33% amino acid identity. Several entry receptors for HSV have been identified. Two of these. HveA (HVEM) and HveC (nectin-1), mediate entry of most HSV-1 and HSV-2 strains and are bound directly by HSV go. A third receptor, HveB (nectin-2), mediates entry of HSV-2 and 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 receptors that mediate PrV and Bf(V-l entry We expressed soluble forms of PrV go and BHV-1 go using recombinant baculoviruses and purified each protein. Using ELISA, we detected direct binding of PrV go to HveB and HveC and direct 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 binding 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 heterologous viruses. These data suggest that the two forms of go bind to a common region on human HveC despite their low amino acid similarity. Based on affinities for human HveC, we predict a porcine HveC homolog may be important 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.