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

Virology. 2001 Feb 1;280(1):7-18. doi: 10.1006/viro.2000.0747.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Viral / metabolism
  • Binding Sites
  • Binding, Competitive
  • CHO Cells
  • Cattle
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • Cricetinae
  • Enzyme-Linked Immunosorbent Assay / methods
  • Herpesvirus 1, Bovine / metabolism*
  • Herpesvirus 1, Human / metabolism*
  • Herpesvirus 1, Suid / metabolism*
  • Humans
  • Nectins
  • Receptors, Virus / metabolism*
  • Solubility
  • Spodoptera / cytology
  • Swine
  • Viral Envelope Proteins / biosynthesis
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism*
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*


  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Cell Adhesion Molecules
  • NECTIN1 protein, human
  • Nectins
  • Receptors, Virus
  • Viral Envelope Proteins
  • Viral Proteins
  • bovine herpesvirus type-1 glycoproteins
  • glycoprotein D, Human herpesvirus 1
  • glycoprotein D, pseudorabies virus