Abstract: Primary microcephaly is a severe brain malformation that leads to a lifelong range of impairments such as intellectual disability, motor, hearing and visual malfunctions. Microcephaly aetiologies vary from genetic abnormalities to external factors such as the STORCH infections (Syphilis, Toxoplasma, Rubella, Cytomegalovirus and Herpes virus). Recently, Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. This talk aims to discuss the alterations in human brain organoids and neurospheres derived from induced pluripotent stem cells infected with ZIKV. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.

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