Zika Virus Infection Induces Cranial Neural Crest Cells to Produce Cytokines at Levels Detrimental for Neurogenesis.
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 its 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.
['Bayless|Nicholas L|NL|', 'Greenberg|Rachel S|RS|', 'Swigut|Tomek|T|', 'Wysocka|Joanna|J|', 'Blish|Catherine A|CA|']
D017209:Apoptosis D001921:Brain D002454:Cell Differentiation D002470:Cell Survival D002478:Cells, Cultured D016207:Cytokines D003716:Dengue Virus D006801:Humans D008954:Models, Biological D009432:Neural Crest D055495:Neurogenesis D000071244:Zika Virus
Zika virus cytokines microcephaly stem cells growth factors neural development