Herpes simplex virus entry receptor

Herpes simplex virus (HSV) entry into cells is mediated by several distinct cell surface molecules collectively known as HSV entry receptors. The main naturally occurring receptors for HSV are heparan sulfate proteoglycans (HSPGs), which serve as initial attachment sites, and protein receptors including nectin-1 (PVRL1), nectin-2 (PVRL2), herpesvirus entry mediator (HVEM/TNFRSF14, a member of the TNF receptor family), and 3-O-sulfated heparan sulfate (3-OS-HS) generated by specific sulfotransferases[1][2][3][7]. Viral envelope glycoproteins, especially gD, interact directly with these protein receptors to trigger membrane fusion and viral entry[1][3]. Some tumor-targeted therapeutic approaches retarget HSV to tumor-specific receptors such as HER2 or IL-13 receptor alpha 2 (IL-13Rα2), enabling highly selective oncolytic virotherapy with modified entry tropism[4][6]. The receptor profile of a tumor determines its susceptibility to HSV infection and oncolytic killing. Differential receptor expression (e.g., only nectin-2) can profoundly affect the cytotoxic efficacy of oncolytic HSV strains[2]. Targeting HSV entry receptors is both a virotherapy strategy and a potential antiviral mechanism, but broad natural expression of the core receptors raises the risk of off-target effects in normal tissues. "HSV entry receptors" is a functional, not a specific molecular, designation referring to multiple cell-surface molecules; thus, it is not a single canonical molecular target but a group of related host proteins.

Other names

Heparan sulfate proteoglycan (HSPG)Nectin-1 (PVRL1)Nectin-2 (PVRL2)Herpesvirus entry mediator (HVEM/TNFRSF14)3-O-sulfated heparan sulfate (3-OS-HS)IL-13 receptor alpha 2 (IL-13Rα2, rare engineered target)Human epidermal growth factor receptor 2 (HER2, engineered/retargeted systems)

Blockade of viral binding (antibodies, competitive ligands for receptor); Retargeted viral entry (engineered HSV using tumor-specific receptors); Heparanase modulation to prevent receptor exposure