Zika congenital syndrome (ZCS), characterized by microcephaly and others neural fetal abnormalities, may affect babies exposed to ZIKA virus (ZIKV) during pregnancy. Since ZIKV infects preferentially neural progenitor cells (NPC), inhibiting its proliferation and differentiation and leading to cell death, we tested ZIKV oncolytic effects in embryonal central nervous system (CNS) tumors with stem-like properties. We demonstrated that ZIKV has the potential to destroy embryonal CNS tumors cell lines and tumorspheres resulting in a massive tumor cell death after three days of infection. In vivo, a single intracerebroventricular injection of ZIKV in BALB/c nude mice bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, decreased tumor burden, fewer metastasis and complete remission in some animals. Furthermore, modulation of WNT signaling pathway significantly increased tumor cell susceptibility to ZIKV oncolytic effects. Nevertheless, the ZIKV tropism towards fetuses' NPC and the involvement of WNT signaling pathway in infection process remains unknown. Genetic and epigenetic modifications could be responsible for activating neural development signaling, as WNT pathway, increasing viral susceptibility and the oncolytic effect in tumor cell are hypothesis to be tested in this project. Elucidating the molecular mechanism of ZIKV infection in normal and tumor cell, as well as developing the ideal conditions for safe human treatment are imperative aiming ZIKV as oncolytic therapy for SNC tumors.
News published in Agência FAPESP Newsletter about the scholarship: