Improvement of Zika virus oncolytic properties aiming central nervous system tumors treatment

• Grant number: 18/16213-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): June 01, 2019
• Effective date (End): January 31, 2022
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Mayana Zatz
• Grantee: Carolini Kaid Dávila
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, RAIANE OLIVEIRA; GRANHA, ISABELA; FERREIRA, RODOLFO SANCHES; BUENO, HELOISA DE SIQUEIRA; OKAMOTO, OSWALDO KEITH; KAID, CAROLINI; ZATZ, MAYANA. Effect of Serial Systemic and Intratumoral Injections of Oncolytic ZIKV(BR) in Mice Bearing Embryonal CNS Tumors. Viruses-Basel, v. 13, n. 10, OCT 2021. (13/08028-1, 19/27784-8, 20/14109-8, 18/16213-7)