Host cell surface receptors for HSV-1 entry

Host cell surface receptors for HSV-1 entry are a diverse group of molecules, including proteins and glycosaminoglycans, that facilitate the attachment and penetration of Herpes Simplex Virus type 1 (HSV-1) into host cells. The entry process begins with the virus attaching to heparan sulfate proteoglycans, followed by the specific binding of viral glycoprotein D (gD) to receptors such as Nectin-1, Herpesvirus entry mediator (HVEM), or 3-O-sulfated heparan sulfate (1.3.1, 1.3.5). This binding triggers a conformational change in the viral glycoproteins, activating the core fusion machinery composed of gB and the gH/gL complex to merge the viral envelope with the host cell membrane (1.2.2, 1.5.2). These receptors are essential for viral tropism, determining the specific cell types, such as epithelial cells and neurons, that the virus can infect and where it establishes latency (1.2.1, 1.2.3). Because they are required for the initial step of the viral life cycle, these receptors are prime targets for the development of entry-blocking antiviral therapies (1.4.1, 1.4.2). Currently, docosanol is an approved topical treatment that acts by interfering with the host cell membrane to inhibit viral fusion, while other experimental agents like RNA aptamers and peptide mimetics are being explored to block specific receptor interactions (1.4.1, 1.4.5). A significant challenge in targeting these receptors is their involvement in critical physiological processes, such as cell-to-cell adhesion and immune signaling regulation (1.2.1, 1.4.2). For instance, HVEM is a key player in T-cell costimulation and coinhibition, meaning its pharmacological modulation could lead to unintended immunological side effects (1.2.1, 1.4.2). Additionally, the expression of Nectin-1 is used as a biomarker to predict the efficacy of oncolytic HSV-1 therapies in treating certain cancers, such as pediatric brain tumors (1.2.1).

Other names

Nectin-1Herpesvirus entry mediatorHVEM3-O-sulfated heparan sulfate3-OS HSPaired immunoglobulin-like type 2 receptor alphaPILR-alphaNon-muscle myosin heavy chain IIANMHC-IIAMyelin-associated glycoproteinMAGHveAHveCPVRL1TNFRSF14

Inhibition of viral envelope fusion with the host cell membrane by interfering with the interaction between viral glycoproteins (such as gD and gB) and host cell surface receptors.