Zika virus unsuspected aide in fighting brain tumors

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Zika virus (ZIKV) is largely known for causing brain abnormalities due to its ability to infect neural proginerator stem cells (NPC) during early development. The nasty virus has now been found to be surprisingly effective in treating two types of childhood brain tumors, as reported by scientists at the University of Sao Paulo in Brazil.

The studies were conducted using human cell lineages derived from two types of embryonic tumors of the central nervous system (CNS): medulloblastoma and atypical teratoid rhabdoid tumor (AT/RT). These are tumors that mainly affect children under 5.

When evaluating the oncolytic properties of Brazilian Zika virus strain (ZIKVBR) against human breast, prostrate, colorectal and embryonal CNS tumor cell lines, the scientists verified a selective infection of CNS tumor cells followed by massive tumor cell death.

ZIKVBR was most efficient in destroying embryonal CNS tumorspheres - a commercial one of medulloblastoma ("DAOY"), and two generated by the researchers themselves, one of medulloblastoma ("USP-13"), and another of AT/RT ("USP-7") - than normal stem cell neurospheres.

In the in vivo experiments, embroynic CNS tumors, which are of human origin, were grafted onto mice. A single intacerebroventricular injection of ZIKVBR in BALB/c nude mico bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, decreased tumor burden, fewer metastasis, and complete remission in some animals.

Specifically, in 20 of 29 animals treated with the Zika virus in the study, the tumors regressed. In seven of them ( five with AT/RT and two with medulloblastoma), the remission was complete: the tumor disappeared. In some cases, the virus was also effective against metastases - it either eliminated the secondary tumor or inhibited its development.

The researchers were also able to relate the effects of the Zika virus to the molecular pathway of Wnt, a pathway that had previously been described as important in the development of AT/RT and medulloblastoma.

"The virus did not effect tumor cells indiscriminately, " explains Okamoto. "It is quite specific for tumor cells of the nervous system.'
In addition, it also did not infect already differentiated neurons, which is a very advantageous behavior if repeated in humans with brain tumor.

"There is a very positive outlook, "says Okamoto. "But thers is a path still toe pursued so that we can move safely into the clinical part."

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