Abstract
Zika virus (ZIKV) is a rapidly emerging flavivirus that has been associated with a number of congenital neurological manifestations. Here, we show that ZIKV replicated efficiently in mouse neural stem cells (mNSCs). ZIKV infection caused a cytopathic effect without affecting cell viability, yet led to a significant decrease in the number of proteins secreted into mNSC supernatants. A gene expression array of neural stem cell progenitor and differentiation markers suggested that infection reduced the number of neuronal and oligodendrocyte progenitors while increasing the number of astrocyte progenitors. Infection in astrocytes increased transcription of key genes involved in the antiviral response. These data provide molecular and cellular evidence that ZIKV significantly alters neural development in the vertebrate host and that astrocyte differentiation may be a protective response that limits neuropathogenesis.
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Acknowledgements
We thank Tonya Colpitts at the University of South Carolina School of Medicine for helping our team develop the experimental aims for this project. Support for this project was provided by the College of Medicine, Field Neurosciences Institute, and the John G. Kulhavi Professorship in Neuroscience at CMU.
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Animals were maintained and procedures were performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Research Council.
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Lossia, O.V., Conway, M.J., Tree, M.O. et al. Zika virus induces astrocyte differentiation in neural stem cells. J. Neurovirol. 24, 52–61 (2018). https://doi.org/10.1007/s13365-017-0589-x
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DOI: https://doi.org/10.1007/s13365-017-0589-x