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.

胶质母细胞瘤是一种高度致死性的脑癌，经常在原始切除腔附近复发。我们探索了溶胶病毒疗法对寨卡病毒（ZIKV）的胶质母细胞瘤的治疗，寨卡病毒（ZIKV）是一种黄病毒，在发育中的胎儿中诱导细胞死亡和神经前体细胞分化。相对于分化的肿瘤后代或正常神经元细胞，ZIKV优先感染并杀死了胶质母细胞瘤干细胞（GSC）。抗GSC的作用不是嗜神经性黄病毒的一般特性，因为西尼罗河病毒会不分皂白地杀死肿瘤细胞和正常神经细胞。ZIKV有效地耗尽了在培养物中和类器官中生长的患者来源的GSC。此外，当用适应小鼠的ZIKV株接种肿瘤时，胶质母细胞瘤小鼠存活的时间更长，且存活率更高。我们的结果表明ZIKV是一种溶瘤病毒，可以优先靶向GSC。因此，进一步优化安全性的转基因菌株对成年胶质母细胞瘤患者可能具有治疗效果。