Nectin cell adhesion molecule 1 and Tumor necrosis factor receptor superfamily member 14 (Nectin-1/HVEM)

Tumor cell entry receptors for oncolytic Herpes Simplex Virus type 1 (oHSV-1) primarily include Nectin-1 (Nectin cell adhesion molecule 1) and Herpesvirus Entry Mediator (HVEM). These surface proteins are the natural receptors utilized by HSV-1 to facilitate viral attachment and membrane fusion through interaction with the viral glycoprotein D (gD) (Campadelli-Fiume et al., 2000). In the context of oncolytic virotherapy, these receptors are critical for the selective entry of therapeutic viruses into malignant cells, with Nectin-1 being frequently overexpressed in various cancers such as melanoma, glioblastoma, and squamous cell carcinoma (Yu et al., 2007). The first FDA-approved oncolytic virus, Talimogene laherparepvec (T-VEC), exploits these natural receptors to infect and lyse tumor cells while stimulating a systemic anti-tumor immune response (Andtbacka et al., 2015). While these receptors facilitate tumor infection, their presence on healthy tissues like neurons and epithelial cells necessitates the use of attenuated viral strains to ensure safety and prevent neurovirulence. Current research also focuses on engineering retargeted oHSVs that bypass these natural receptors to target tumor-specific antigens like HER2 or EGFR, thereby enhancing therapeutic specificity (Menotti et al., 2009).

Other names

PVRL1CD111HveCTNFRSF14CD270HveAHVEMNectin-1Herpesvirus entry mediatorTumor cell entry receptors for oncolytic HSV1

Viral glycoprotein D (gD) binds to Nectin-1 or HVEM, triggering conformational changes in gB and the gH/gL complex to mediate membrane fusion and viral entry into the host cell.