Zika Virus Has Oncolytic Activity against Glioblastoma Stem Cells

We explored the utility of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells (GSCs) relative to differentiated tumor progeny or normal neuronal cells. The effects against GSCs were not a general property of neurotropic flaviviruses, as West Nile Virus (WNV) indiscriminately killed both tumor and normal neural cells. ZIKV potently depleted patient-derived GSCs grown in culture and in organoids. Moreover, mice with glioblastoma survived substantially longer and at greater rates when the tumor was inoculated with a murine adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs, and thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients. RNA-seq of glioblastoma stem cells and non-stem tumor cells. These samples have not been infected with Zika virus.