Zika virus E protein dysregulate mir-204/WNT2 signalling in human fetal neural stem cells

Zika Virus (ZIKV) belongs to the family of flaviviruses, and is neurotrophic. It has been known to cause severe congenital disabilities including microcephaly in neonates. The virus has a specific preference towards neural stem cells (NSCs). ZIKV impairs proliferation and differentiation of NSCs during in-utero brain development of the fetus. However, molecular pathways involved in ZIKV induced alteration in NSCs are yet to be explored. In our previous study, we have described that ZIKV E protein dysregulates microRNA circuitry in NSCs and also impairs their proliferative and differentiation abilities. WNT signalling was found to be the target of differentially expressed miRNAs as suggested by PANTHER PATHWAY analysis of differentially expressed miRNA targets. In our current follow-up study, we investigate that WNT2 is downregulated in response to ZIKV E protein in human fetal NSCs and WNT2 is the molecular target of microRNA miR-204-5p. We provide pieces of evidences that miR-204-5p/WNT2 axis is involved in ZIKV induced impairment in the proliferation and immature differentiation of neural stem cells.