A bright side of Zika: potent and selective oncolytic properties against aggressive human CNS embryonal tumors

Zika virus (ZIKV) is largely known for causing brain abnormalities due to its ability to infect neural progenitor stem cells (NPC) during early development. Here we show that ZIKV is also capable of infecting and destroying stem-like cancer cells from aggressive human embryonal tumors of the central nervous system (CNS). When evaluating the oncolytic properties of Brazilian Zika virus strain (ZIKVBR) against human breast, prostate, colorectal and embryonal CNS tumor cell lines, a selective infection of CNS tumor cells, followed by a massive necrotic tumor cell death, was verified. Notably, ZIKVBR was more efficient in destroying CNS tumorspheres than normal stem cell neurospheres. A single intracerebroventricular injection of ZIKVBR in BALB/c nude mice bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, reduced tumor burden, fewer metastasis and complete remission in some animals. Tumor cells closely resembling neural stem cells at the molecular level were more susceptible to ZIKVBR oncolytic effects. Altogether, these preclinical findings indicate that ZIKV could be an efficient oncolytic agent to treat aggressive forms of embryonal CNS tumors. Considering the poor effectiveness and severe side effects of available treatments for these tumors and that most ZIKV infections are asymptomatic, our findings open new avenues for novel therapies.

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