Herpesvirus entry mediator (HVEM) is also known as TNFRSF14, TR2 (TNF receptorlike molecule) and ATAR (another TRAF associated receptor), is a type I membrane protein belonging to the TNF/NGF receptor superfamily. HVEM expression has been detected in peripheral blood T cells, B cells, monocytes and in various tissues enriched in lymphoid cells. The extracellular domain of HVEM has been shown to interact directly with the herpes simplex virus envelope glycoprotein D (gD). Two TNF superfamily ligands, including the secreted TNFβ (lymphotoxin α) and the membrane protein LIGHT (lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes), have been shown to be the cellular ligands for HVEM. Besides HVEM, LIGHT can also interact with LTβR, the receptor for lymphotoxin αβ heterotrimer. The role of the HVEM LIGHT /LTβ receptor ligand pair in immune function and herpesvirus pathobiology remains to be elucidated.
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