Zika virus (ZIKV) infection during pregnancy is linked to microcephaly, which is attributed to
infection of developing brain structures. ZIKV infects neural progenitor cells in vitro, though it’s effects on other developmentally relevant stem cell populations, including cranial neural crest cells
(CNCCs), have not been assessed. CNCCs give rise to most cranial bones and exert paracrine
effects on the developing brain. Here, we report that CNCCs are productively infected by ZIKV,
but not by the related dengue virus. ZIKV-infected CNCCs undergo limited apoptosis but secrete
cytokines that promote death and drive aberrant differentiation of neural progenitor cultures. Addition of two such cytokines, LIF or VEGF, at levels comparable to those secreted by ZIKV-infected
CNCCs is sufficient to recapitulate premature neuronal differentiation and apoptotic death of
neural progenitors. Thus, our results suggest that CNCC infection by ZIKV may contribute to associated embryopathies through signaling crosstalk between developing face and brain structures.
Zika virus (ZIKV), an arbovirus of the Flaviviridae family first isolated in Uganda in 1947, has recently undergone a major outbreak in Latin American countries, where it has been linked to significant adverse fetal outcomes including microcephaly (Brasil et al., 2016). A significant effort has subsequently been devoted to defining mechanisms underlying the developmental
abnormalities that lead to microcephaly, with the focus on the direct effects of ZIKV infection on growth and survival of the neural progenitor cells (NPCs), whose expansion or decline ultimately affects brain size. These studies demonstrated that ZIKV infects human NPCs and in vitro-derived brain organoids,