Although we've a compelling spatial-temporal link between Zika virus outbreaks and increases in microcephaly in Brazil (and to a lesser extent in French Polynesia), we still lack proof of causation.
One of the many barriers to proving causation is finding a plausible mechanism by which the Zika virus could produce the kind of profound fetal brain anomalies that have been reported.
Today, in a brief report published in the journal Cell Stem Cell, researchers working with lab-grown human stem cells have shown the Zika virus selectively infects the type of cells that form the brain’s cortex, and importantly, infection `increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth.'
The full report can be accessed at the link below. Below that you'll find a link and some excerpts from a press release.
Publication stage: In Press Corrected Proof
- •Zika virus (ZIKV) infects human embryonic cortical neural progenitor cells (hNPCs)
- •ZIKV-infected hNPCs produce infectious ZIKV particles
- •ZIKV infection leads to increased cell death of hNPCs
- •ZIKV infection dysregulates cell cycle and transcription in hNPCs
SummaryThe suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells.
Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target.
In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.
The Zika virus infects a type of neural stem cell that gives rise to the brain's cerebral cortex, Johns Hopkins and Florida State researchers report March 4 in Cell Stem Cell. On laboratory dishes, these stem cells were found to be havens for viral reproduction, resulting in cell death and/or disruption of cell growth.
While this study does not prove the direct link between Zika and microcephaly, it does pinpoint where the virus may be doing the most damage.
The researchers, led by Guo-li Ming and Hongjun Song of the Johns Hopkins University School of Medicine and Hengli Tang of Florida State University, with collaborators at the Emory University School of Medicine, worked around the clock for a month to conduct the study, which provides a new platform to learn about the Zika virus using neuronal cells derived from human induced pluripotent stem cells. In the near future, the researchers hope to grow mini-brains from the stem cells to observe the long-term effects of Zika infection on neural tissue and to screen for potential therapeutics.
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### This study was supported by The Florida State University, the National Institutes of Health, and the Maryland Stem Cell Research Fund.