Herpes simplex virus type 1 entry receptors (HSV-1 entry receptors)

Herpes simplex virus type 1 (HSV-1) entry receptors on tumor cells are a group of cell surface proteins that facilitate the attachment and fusion of HSV-1 with the host cell membrane. The primary receptors involved are Nectin-1 (also known as HveC or PVRL1) and Herpesvirus entry mediator (HVEM, also known as HveA or TNFRSF14), which bind to the viral envelope glycoprotein D (gD) [PubMed: 10623592]. In the field of oncology, these receptors are exploited by oncolytic HSV (oHSV) therapies, such as Talimogene laherparepvec (T-VEC), to selectively target and infect malignant cells [PubMed: 26024816]. Many cancers, including melanoma, glioblastoma, and squamous cell carcinoma, overexpress Nectin-1, providing a high degree of selectivity for viral entry and subsequent oncolysis [PubMed: 15150593]. Once the virus enters the tumor cell via these receptors, it replicates, leading to direct cell death and the release of progeny virions and tumor-associated antigens. This process not only destroys the primary tumor but also triggers a systemic anti-tumor immune response, making these receptors critical components of the therapeutic mechanism [PubMed: 27050146]. The interaction between the viral gD and these host receptors is the rate-limiting step for viral infection and determines the tropism of the oncolytic agent.

Other names

Nectin-1Herpesvirus entry mediator (HVEM)HveCHveAPVRL1TNFRSF143-O-sulfated heparan sulfatePoliovirus receptor-related protein 1Nectin-2HveB

Binding of viral glycoprotein D to host receptors (Nectin-1, HVEM) to facilitate viral entry, followed by selective viral replication in tumor cells, induction of immunogenic cell death, and stimulation of a systemic anti-tumor immune response [PubMed: 26024816, 27050146].