Zika Virus Infection Induces Cranial Neural Crest Cells to Produce Cytokines at Levels Detrimental for Neurogenesis

Nicholas L Bayless; Rachel S Greenberg; Tomek Swigut; Joanna Wysocka; Catherine A Blish

doi:10.1016/j.chom.2016.09.006

Zika Virus Infection Induces Cranial Neural Crest Cells to Produce Cytokines at Levels Detrimental for Neurogenesis

Cell Host Microbe. 2016 Oct 12;20(4):423-428. doi: 10.1016/j.chom.2016.09.006. Epub 2016 Sep 29.

Authors

Nicholas L Bayless¹, Rachel S Greenberg², Tomek Swigut³, Joanna Wysocka⁴, Catherine A Blish⁵

Affiliations

¹ Stanford Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA.
² Department of Developmental Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA.
³ Department of Developmental Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Developmental Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA; Institute of Stem Cell Biology and Regenerative Medicine, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: wysocka@stanford.edu.
⁵ Stanford Immunology, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA; Department of Medicine, Stanford School of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: cblish@stanford.edu.

Abstract

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.

Keywords: Zika virus; cytokines; growth factors; microcephaly; neural development; stem cells.

MeSH terms

Apoptosis
Brain / embryology
Cell Differentiation / drug effects
Cell Survival / drug effects
Cells, Cultured
Cytokines / metabolism*
Dengue Virus / growth & development
Humans
Models, Biological
Neural Crest / metabolism*
Neural Crest / virology*
Neurogenesis / drug effects*
Zika Virus / growth & development*

Substances

Cytokines

Abstract

MeSH terms

Substances

Grants and funding