Tumor cell surface HSV-1 entry receptors

Tumor cell surface HSV-1 entry receptors are a group of host cell proteins and molecules that facilitate the attachment and entry of Herpes Simplex Virus type 1 (HSV-1) into target cells. The primary receptors involved in this process include Nectin-1 (CD111/PVRL1), Herpesvirus Entry Mediator (HVEM/TNFRSF14), and 3-O-sulfated heparan sulfate, which interact specifically with the viral envelope glycoprotein D (gD) to initiate membrane fusion [1.1.1, 1.1.3]. In the context of oncology, these receptors are the essential targets for oncolytic HSV-1 (oHSV) therapies, such as the FDA-approved Talimogene laherparepvec (T-VEC) [1.1.2, 1.2.2]. Nectin-1 is particularly significant as it is frequently overexpressed in various malignancies, including melanoma and glioblastoma, serving as a key determinant of viral tropism and therapeutic success [1.1.2, 1.2.1]. While these receptors are also present on some normal cells, oHSVs are typically genetically attenuated (e.g., by deleting the ICP34.5 gene) to ensure that productive viral replication and subsequent oncolysis occur selectively within the tumor microenvironment [1.2.2, 1.2.3]. Monitoring the expression of these receptors, particularly Nectin-1, serves as a potential biomarker for predicting patient response to oHSV treatment [1.1.2]. Therapeutic challenges include the potential for off-target infection and the development of neutralizing antibodies that can limit the efficacy of repeated viral administrations [1.2.2].

Other names

Nectin-1Herpesvirus entry mediatorHVEM3-O-sulfated heparan sulfateCD111TNFRSF14PVRL1HveAHSV-1 entry receptorsNectin-2PVRL2CD112

Oncolytic viruses enter tumor cells by binding to these surface receptors via viral glycoprotein D, leading to selective viral replication, tumor cell lysis, and the release of tumor-associated antigens that stimulate a systemic anti-tumor immune response [1.1.1, 1.2.2].