Unraveling Zika virus-induced cell death pathways in eradicating embryonal central nervous system tumors

The Zika virus (ZIKV) has gained attention due to its link with causing congenital syndrome, which is characterized by microcephaly as a significant symptom. The neurotropism of the virus is not limited to neural progenitor cells; ZIKV has also been tested as an oncolytic virus, given its affinity for tumor cells in the central nervous system. Understanding the cell death pathway involved in eliminating tumor cells is crucial to determining whether ZIKV triggers a silent or immunogenic response in the nervous tissue, which could potentially harm the surrounding healthy tissue. Hence, this study investigated the cell death pathways in human embryonal central nervous tumor cells that were either infected or not infected with ZIKV using in vitro assays. The cells were treated with specific inhibitors of proteins associated with apoptosis, necroptosis, and pyroptosis and then analyzed using flow cytometry and Western blotting. The results demonstrated that these cells could activate apoptosis, necroptosis and pyroptosis as cell death pathways. However, unlike the blockers for necroptosis and pyroptosis proteins, only caspase inhibition with Q-VD-OPh successfully protects all cells from dying after ZIKV infection. ZIKV predominantly induces apoptosis to eradicate central nervous tumor cells promoting low immunogenic profile, which suggests that ZIKV can effectively infect and eliminate tumor cells while sparing surrounding healthy tissue.