Tumor cell machinery for Herpes Simplex Virus replication and entry

Tumor cell machinery for Herpes Simplex Virus (HSV) replication and entry refers to the host cell factors that oncolytic HSV (oHSV) therapies exploit to selectively target and eliminate cancer cells. The entry of HSV into tumor cells is primarily mediated by the interaction of viral glycoprotein D (gD) with specific host receptors, most notably Nectin-1 (PVRL1) and Herpesvirus Entry Mediator (HVEM), which are frequently overexpressed in various malignancies such as melanoma and glioblastoma (Campadelli-Fiume et al., 2016, PMID: 27131335). Once the virus has entered the cell, its replication is facilitated by the tumor's high metabolic state and its often-defective antiviral signaling pathways, such as the Type I Interferon (IFN) response and the Protein Kinase R (PKR) pathway (Peters & Rabkin, 2015, PMID: 26154618). Therapeutic agents like Talimogene laherparepvec (T-VEC) are engineered to be tumor-selective by deleting genes like ICP34.5, which normally counteracts the host cell's shut-off of protein synthesis; in normal cells, these viruses cannot replicate, but in cancer cells with dysregulated signaling, replication proceeds (Kaufman et al., 2015, PMID: 26334835). This selective replication leads to direct oncolysis, releasing progeny virions and tumor-associated antigens into the microenvironment. This process not only destroys the primary tumor but also stimulates a systemic, immune-mediated anti-tumor response, often enhanced by the viral expression of cytokines like GM-CSF (Andtbacka et al., 2015, PMID: 26014293). Safety concerns include the potential for off-target infection and the development of neutralizing antibodies that may limit therapeutic efficacy.

Other names

oHSV targetsHSV entry receptorsOncolytic HSV replication factorsHost factors for HSV infectionNectin-1/HVEM entry complex

Selective viral entry via tumor-associated receptors followed by replication-induced oncolysis and immune activation.