Zika virus capsid protein impairs neural differentiation

Zika virus (ZIKV) is causally associated with serious neurological complications such as microcephaly. The underlying mechanism is still not clear. Here, mouse embryonic stem cells (mESCs) were used to explore the role of ZIKV capsid protein in two neural differentiation models. Both immature anchor capsid and mature capsid proteins do not affect the pluripotency and cell cycle of mESCs, barely impair the ability of spontaneous embryoid body to differentiate into three germ layers, but significantly compromise the neural differentiation. In transcriptomic analysis, genes associated with axon guidance, Wnt signaling pathway, MAPK signaling pathway, and TGF-beta signaling pathway were commonly downregulated by capsid protein in two neural differentiation models, whereas the genes associated with p53 signaling pathway and ECM-receptor interactions were commonly upregulated by capsid protein. The results highlight the critical role of ZIKV capsid protein in neural differentiation, and provide valuable resources for in-depth understanding of ZIKV-induced neuropathogenesis.