VPA is a histone deacetylase inhibitor whose carboxylic acid moiety contributes to zinc chelation within the HDAC catalytic pocket, leading to chromatin relaxation and reactivation of silenced tumor suppressor and immunomodulatory genes. This sensitizes tumors to OV infection. In combination with oHSV, VPA suppresses NK cell cytotoxicity by inhibiting STAT5 phosphorylation and T-BET expression, reducing IFN-γ production and enhancing viral persistence and antitumor efficacy. This evidence concerns the gene DNER and infection.