Herpes simplex virus type 1 (HSV-1) is an ~152 kb double-stranded DNA virus that infects over half of the population. As an abiotic obligate parasite, HSV-1 uses cellular factors for propagation. Our lab previously found that DNA Ligase III (Lig3) associates with HSV-1 DNA. Lig3 is a eukaryotic, ATP-dependent enzyme that facilitates phosphodiester bond formation to anneal single strand nicks that form during DNA repair and Okazaki fragments during DNA replication. We hypothesize that HSV-1 recruits cellular Lig3 to help facilitate viral DNA replication or repair and predict that Lig3 knockdown will decrease viral yield. We identified an antibody targeting Lig3, confirmed that Lig3 levels remain consistent during infection, and optimized siRNA-mediated Lig3 knockdown conditions. We also determined how Lig3 knockdown affects viral yield through plaque assays. Data demonstrate a two-fold decrease in viral yield, indicating that cellular Lig3 may play an important role in HSV-1 infection.