HVEM acts as both a receptor for the canonical TNF-related ligands, LIGHT [lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed on T lymphocytes] and lymphotoxin-α, and as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules.
For instance, soluble BTLA, LTα, and LIGHT inhibited the binding of wild-type gD to HVEM, and soluble BTLA and LTα blocked HSV infection of HVEM-expressing cells.
Herpes virus entry mediator (HVEM) plays a critical role in the regulation of inflammation through interaction with its natural ligands LIGHT and lymphotoxin alpha and also serves as one of the entry receptors of herpes simplex virus (HSV).