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 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 gD 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 gD. 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 gD from PrV and BHV-1 binds directly to the human receptors that mediate PrV and BHV-1 entry. We expressed soluble forms of PrV gD and BHV-1 gD using recombinant baculoviruses and purified each protein. Using ELISA, we detected direct binding of PrV gD to HveB and HveC and direct binding of BHV-1 gD to HveC. Biosensor analysis revealed that PrV gD had a 10-fold higher affinity than HSV-1 gD for human HveC. In contrast, the binding of BHV-1 gD to HveC was weak. PrV gD and HSV-1 gD 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 gD 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 PrV 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.
Connolly
S A
SA
Department of Microbiology, School of Dental Medicine, University of Pennsylvania, Philadelphia 19104, USA. sconnoll@mail.med.upenn.edu
Whitbeck
J J
JJ
Rux
A H
AH
Krummenacher
C
C
van Drunen Littel-van den Hurk
S
S
Cohen
G H
GH
Eisenberg
R J
RJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D016466:CHO Cells; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D007242:Herpesvirus 1, Bovine / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000378:metabolism*; D011558:Herpesvirus 1, Suid / Q000378:metabolism*; D006801:Humans; D000075983:Nectins; D011991:Receptors, Virus / Q000378:metabolism*; D012995:Solubility; D018411:Spodoptera / Q000166:cytology; D013552:Swine; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015815:Cell Adhesion Molecules; C000619010:NECTIN1 protein, human; D000075983:Nectins; D011991:Receptors, Virus; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C046998:bovine herpesvirus type-1 glycoproteins; C039447:glycoprotein D, Human herpesvirus 1; C107752:glycoprotein D, pseudorabies virus