Herpesvirus entry mediator (HVEM) (HVEM)

The Herpesvirus entry mediator (HVEM), also known as HveA or TNFRSF14, is a type I transmembrane glycoprotein belonging to the tumor necrosis factor receptor superfamily and serves as a key cellular receptor for herpes simplex virus (HSV) entry into host cells. HVEM binds directly to HSV envelope glycoprotein D (gD), triggering conformational changes that activate the viral fusion machinery, including gB, gH, and gL, to facilitate pH-independent membrane fusion and nucleocapsid release into the cytoplasm. This interaction is essential for HSV-1 and HSV-2 infection across various cell types, though HVEM works alongside other receptors like nectin-1 for broader tropism. Beyond viral entry, HVEM engages in bidirectional signaling as both a receptor and ligand, interacting with immune modulators such as BTLA, CD160, and LIGHT to regulate NF-κB activation, T cell costimulation, and inflammatory responses. In disease contexts, HVEM primarily enables herpesvirus infections, including initial infection and cell-to-cell spread, making it a focal point for understanding HSV pathogenesis in neurons and epithelial tissues. While no approved drugs directly target HVEM, structural insights into its gD-binding interface inform antiviral strategies, though its immune roles pose potential challenges for therapeutic modulation.

Other names

HveATNFRSF14