Herpes simplex virus entry receptors (HSV entry receptors)

Tumor cell surface receptors for HSV entry, primarily Nectin-1 (PVRL1) and Herpesvirus entry mediator (HVEM/TNFRSF14), are the essential cellular proteins exploited by Herpes Simplex Virus (HSV) to initiate infection and membrane fusion. These receptors interact with the viral envelope glycoprotein D (gD), triggering a cascade of conformational changes in other viral glycoproteins (gH/gL and gB) that culminate in the fusion of the viral envelope with the host cell membrane. In the field of oncology, these receptors serve as the primary gateways for oncolytic HSV (oHSV) therapies, such as the FDA-approved Talimogene laherparepvec (T-VEC). The selective expression of Nectin-1 in various malignancies, including melanoma and glioblastoma, facilitates the preferential infection and subsequent lysis of tumor cells by these engineered viruses. Beyond direct oncolysis, the interaction with these receptors allows the virus to deliver therapeutic payloads, such as GM-CSF, which enhance the systemic anti-tumor immune response. Monitoring the expression levels of Nectin-1 and HVEM is increasingly recognized as a vital strategy for predicting patient response to oHSV treatments.

Other names

Nectin-1Herpesvirus entry mediatorHVEMPVRL1TNFRSF14HveAHveCCD111CD2703-O-sulfated heparan sulfatePoliovirus receptor-related protein 1

Oncolytic virotherapy: Viral entry is mediated by the binding of viral glycoprotein D to Nectin-1 or HVEM on the tumor cell surface. This triggers membrane fusion and viral entry, followed by selective replication within the tumor cell (often facilitated by deletions in neurovirulence genes like ICP34.5), leading to direct oncolysis and the release of tumor antigens and immunostimulatory cytokines to induce a systemic anti-tumor immune response.