Calcium dynamics evoked by oncolytic herpes simplex virus infection of human tumor cells: In vitro experiments and mathematical modeling

Tumor eradication using oncolytic viruses represents a promising therapeutic strategy. Herpes simplex virus (HSV) has been extensively studied in this context due to its ability to preferentially replicate in cancer cells while simultaneously eliciting antitumor immune responses. Binding of oncolytic HSV (oHSV) to the cell membrane initiates a cascade of intracellular signaling events, including the release of calcium from intracellular stores. This thesis project aims to investigate calcium signaling dynamics in HeLa DH cells stably expressing the genetically encoded calcium indicator GCaMP6s following in vitro infection with oHSV. To gain mechanistic insight into the observed calcium dynamics, we will further employ a mathematical modeling approach to reproduce the experimentally acquired signals. This combined data-driven and theoretical strategy will enable exploration of the molecular mechanisms underlying virus-induced calcium signaling and facilitate the identification of key components governing the cellular response to oHSV infection. To test the hypotheses emerging from the model and dissect the signaling pathway involved, we will use a pharmacological approach targeting different molecular steps.