Herpes simplex virus type 2 entry receptors

The target refers to the cellular receptors and mechanisms that allow Herpes Simplex Virus type 2 (HSV-2) to enter and infect both host and tumor cells. This process is primarily mediated by the interaction between viral envelope glycoproteins, specifically glycoprotein D (gD), and host cell surface receptors such as Nectin-1 (PVRL1) and Herpesvirus Entry Mediator (HVEM/TNFRSF14) [1][2]. Nectin-1 is a cell-adhesion molecule frequently overexpressed in various cancers, including squamous cell carcinomas and melanomas, making these cells highly permissive to HSV-2 infection [3]. In the context of oncology, this permissivity is exploited by oncolytic HSV-2 (oHSV-2) therapies, which are engineered to selectively replicate in and destroy malignant cells while inducing a systemic immune response against the tumor [4]. These therapies, such as the drug candidate OH2, utilize the virus's natural affinity for these receptors to achieve targeted oncolysis [5]. The interaction triggers a cascade involving other glycoproteins like gH/gL and gB to facilitate membrane fusion and viral entry [1]. Clinical development focuses on enhancing the safety of these interactions by deleting viral virulence genes while maintaining the ability to infect permissive tumor cells [4]. Monitoring the expression of Nectin-1 and HVEM can serve as a biomarker for identifying patients most likely to benefit from these oncolytic treatments [3].

Other names

Nectin-1Poliovirus receptor-related protein 1 (PVRL1)Herpesvirus entry mediator (HVEM)Tumor necrosis factor receptor superfamily member 14 (TNFRSF14)CD111CD2703-O-sulfated heparan sulfateHveAHveC

Oncolytic viruses utilize native viral glycoproteins (gB, gC, gD, gH/gL) to bind to host cell receptors like Nectin-1 and HVEM, facilitating viral entry, selective replication within tumor cells, and subsequent immunogenic cell death (oncolysis).