Tumor cells permissive to Herpes Simplex Virus type 2 replication

Tumor cells permissive to Herpes Simplex Virus type 2 (HSV-2) replication are malignant cells characterized by their ability to support the complete viral life cycle, making them the primary substrate for oncolytic HSV-2 (oHSV-2) therapies. This permissiveness is largely determined by the surface expression of entry receptors such as Nectin-1 (CD111) and the Herpesvirus entry mediator (HVEM), as well as the presence of intracellular defects in antiviral signaling pathways, particularly the Type I Interferon (IFN) response (Krummenacher et al., 2004; Xia et al., 2016). In clinical oncology, modified HSV-2 strains like OH2 are designed to exploit these vulnerabilities, selectively replicating within the tumor microenvironment to induce direct cell death through oncolysis (Zhang et al., 2021). Beyond direct destruction, the replication process releases progeny virions and tumor-derived antigens, effectively turning the tumor into an in situ vaccine that promotes a systemic immune response against the cancer (Liu et al., 2020). While this 'target' is a cellular phenotype rather than a single molecule, its identification is crucial for the successful application of virotherapy in solid tumors. Therapeutic challenges include the potential for pre-existing antiviral immunity to neutralize the virus before it can reach the permissive cells and the risk of off-target infection in non-malignant tissues.

Other names

HSV-2 susceptible tumor cellsOncolytic HSV-2 targetsPermissive malignant cellsHSV-2 infected cancer cells

Selective viral replication within permissive tumor cells leads to direct oncolysis (cell bursting) and the release of tumor-associated antigens, which triggers a systemic anti-tumor immune response.