biostudies-literature00540Zhu ZNational Center for Advancing Translational SciencesNational Center for Research ResourcesNCATS NIH HHSCancer Research FoundationNIAID NIH HHSNational Institutes of HealthNIHWashington UniversityNCIConcern FoundationNINDS NIH HHSNCI NIH HHSElsa U. Pardee FoundationNIGMS NIH HHS2843-2857https://www.ebi.ac.uk/biostudies/studies/S-EPMC5626408biostudies-literatureUnknown214(10)Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use 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 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 mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.The Journal of experimental medicineZika virus has oncolytic activity against glioblastoma stem cells.PMC5626408R01 CA154130R01 NS087913UL1 TR002345R01 AI104972NS087913R01 NS103434UL1 TR000448R35 CA197718P50 CA094056R01 NS089272T32 GM007250P30 CA091842CA197718CA169117P30 CA91842R01 CA169117R01 CA171652CA154130NS089272CA171652UL1TR000448R01 AI073755Gorman MJDiamond MSZhu ZMcKenzie LDRich JNPrager BCRichner JMFernandez EChheda MGShan CZhang RHubert CGTycksen EChai JNShi PYWang X54falseZika virus has oncolytic activity against glioblastoma stem cells.Glioblastoma is a highly lethal brain cancer that frequently recurs in proximity to the original resection cavity. We explored the use 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 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 mouse-adapted strain of ZIKV. Our results suggest that ZIKV is an oncolytic virus that can preferentially target GSCs; thus, genetically modified strains that further optimize safety could have therapeutic efficacy for adult glioblastoma patients.2017-01-01T00:00:00Z2017 Oct2024-11-09T15:26:52.932Z2019-06-06T18:12:32ZS-EPMC56264082887439210.1084/jem.20171093