The three HveA receptor ligands, gD, LT-alpha and LIGHT bind to distinct sites on HveA

Mol Immunol. 2000 Aug;37(11):665-73. doi: 10.1016/s0161-5890(00)00089-4.


The herpes virus entry mediator A (HveA), a member of the tumor necrosis factor receptor (TNFR) superfamily, interacts with three different protein ligands; lymphotoxin-alpha (LT-alpha) and LIGHT (LIGHT stands for lymphotoxin homolog, which exhibits inducible expression and competes with HSV glycoprotein D for HveA and is expressed on T-lymphocytes) from the host and the herpes simplex virus (HSV) surface glycoprotein gD. It has been reported that the gD binding site on HveA is located within the receptor's two N-terminal CRP domains, and that gD and LIGHT compete for their binding to HveA. However, whether these ligands interact with the same or different sites on the receptor is unclear. We analyzed and compared the sites of interaction between HveA and its TNF ligands, by using two recombinant forms of the receptor, comprising the full-receptor ectodomain (HveA (200t)) and its two first CRP domains (HveA (120t)), as well as several monoclonal antibodies recognizing HveA. Two HveA peptide ligands (BP-1 and BP-2) that differentially inhibit binding of soluble gD and LT-alpha to the receptor were also used to demonstrate that gD, LIGHT and LT-alpha bind to distinct sites on the receptor. Our results suggest that binding of a ligand to HveA may alter the conformation of this receptor, thereby affecting its interaction with its other ligands.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Binding Sites
  • Binding, Competitive
  • Lymphotoxin-alpha / metabolism*
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Member 14
  • Receptors, Virus / metabolism*
  • Sodium Chloride / pharmacology
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factor-alpha / metabolism*
  • Viral Envelope Proteins / metabolism*


  • Antibodies, Monoclonal
  • Lymphotoxin-alpha
  • Membrane Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 14
  • Receptors, Virus
  • TNFRSF14 protein, human
  • TNFSF14 protein, human
  • Tnfrsf14 protein, mouse
  • Tnfsf14 protein, mouse
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factor-alpha
  • Viral Envelope Proteins
  • glycoprotein D, Human herpesvirus 1
  • Sodium Chloride