Host cell receptors used for HSV-1 entry

Host cell receptors used for HSV-1 entry are a group of diverse surface molecules that facilitate the attachment and penetration of Herpes Simplex Virus type 1 into host cells [1, 11]. The entry process is initiated by the binding of viral glycoproteins gB and gC to heparan sulfate proteoglycans (HSPGs) for initial attachment [4, 5]. Subsequently, the viral glycoprotein D (gD) binds to one of several specific entry receptors, including Nectin-1 (PVRL1), Herpesvirus Entry Mediator (HVEM/TNFRSF14), or 3-O-sulfated heparan sulfate (3-OS HS) [3, 11, 15]. This binding triggers a conformational change in gD that activates the core fusion machinery—comprising gB and the gH/gL complex—to mediate fusion between the viral envelope and the host cell membrane [13, 17]. Additional receptors such as PILR-alpha, NMHC-IIA, and certain integrins may also interact with gB or gH/gL to facilitate entry in a cell-type-specific manner [12, 14, 16]. Targeting these receptors or their interactions with viral glycoproteins is a key strategy for developing entry inhibitors, such as docosanol, which is used topically to treat herpes labialis by interfering with the fusion process [2, 7]. These receptors are critical for viral pathogenesis, and their expression patterns determine the tissue tropism of HSV-1, including its ability to infect epithelial cells and establish latency in neurons [11, 19].

Other names

Nectin cell adhesion molecule 1Tumor necrosis factor receptor superfamily member 143-O-sulfated heparan sulfateNectin cell adhesion molecule 2Paired immunoglobulin-like type 2 receptor alphaMyosin heavy chain 9Myelin-associated glycoproteinIntegrin alpha-V beta-6Integrin alpha-V beta-8HveAHveBHveCHVEMPVRL1PVRL2PILRAMYH9MAG3-OS HS

Inhibition of viral fusion with the host cell membrane; competitive inhibition of viral glycoprotein binding to host receptors; modification of host cell membrane properties to prevent viral entry.