Tumor cells permissive to Herpes simplex virus 1 infection

Tumor cells permissive to HSV-1 infection represent a specific cellular phenotype targeted by oncolytic herpes simplex virus (oHSV) therapies. These cells are characterized by the expression of viral entry receptors, most notably Nectin-1 (CD111) and Herpesvirus Entry Mediator (HVEM), which facilitate the binding and fusion of the HSV-1 envelope with the host cell membrane (Campadelli-Fiume et al., 2007). Beyond entry, permissivity is often driven by oncogenic signaling pathways (e.g., Ras) or deficiencies in innate antiviral defenses, such as the interferon (IFN) response and the Protein Kinase R (PKR) pathway, which allow the virus to bypass normal cellular growth arrest and replicate selectively within the malignancy (Mohl et al., 2016). The primary therapeutic agent targeting these cells is Talimogene laherparepvec (T-VEC), a modified HSV-1 that replicates within permissive tumor cells to induce direct oncolysis and the release of granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate a systemic immune response (Rehman et al., 2016). This process converts the "cold" tumor microenvironment into an "immunologically hot" one, facilitating a systemic T-cell mediated anti-tumor response. Understanding the molecular profile of these permissive cells is critical for patient selection and improving the efficacy of virotherapy in various cancers, including melanoma and glioma. Safety concerns include the potential for off-target infection in non-permissive healthy tissues and the risk of viral shedding to close contacts.

Other names

HSV-1 susceptible tumor cellsoHSV-permissive cancer cellsNectin-1 expressing tumor cellsHVEM-positive tumor cells

Selective viral replication within tumor cells leading to direct oncolysis and induction of a systemic anti-tumor immune response.