Abstract
Previous studies have demonstrated that the tropism of Zika virus (ZIKV) for human neural stem cells (NSCs) leads to severe brain malformations. The proposed mechanisms underlying these brain malformations are thought to include the induction of apoptosis in neural progenitor/stem cells (Zhang et al., Nucleic Acid Res. 44:8610–8620, 2016). Previously, we observed many similarities between NSCs and brain tumor stem cells (BTSCs) (Wu et al., Stem Cells Dev., 17:173–184, 2008) and sought to determine if BTSC could support ZIKV replication. ZIKV infection of skin cells in vitro is mediated by the receptors AXL, DC-SIGN, TIM1, and TYRO3 (Hamel et al., J Virol. 89:8880–8896, 2015). We examined human embryonic brain tissue and have observed that the putative ZIKV receptor TIM1 is expressed by neuronal and astrocytic progenitor cells. Given the similarities between NSCs and BTSCs we examined human and rodent brain tumor cells for putative ZIKV receptor expression. We found TIM1 expression by human GBM6 glioma cells and murine GL261 gliomas. In tissue culture studies, incubation of ZIKV with human GBM6 cells led to high levels of infection. To determine the effects of ZIKV on tumor growth in vivo, we transplanted GL261 cells into the striatal area of the brain in syngeneic C57B/6 mice. Intra-tumoral injections of ZIKV were administered immediately after intra-cranial tumor implantation. Tumor-bearing mice receiving intra-tumoral injections of ZIKV exhibited prolonged survival in comparison to untreated mice. Together these results suggest that ZIKV may have potential as an oncolytic virus for targeting malignant brain tumors. (This work was supported in part by a grant from the Randy Shaver Cancer Research Foundation).