Zika virus tested in brain precursor cells
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Zika virus preferentially kills developing brain cells, a new study reports. The results offer evidence for how Zika virus may cause brain defects in babies—and specifically microcephaly, a rare birth defect in which the brain fails to grow properly.
Brazil is in the midst of an unprecedented epidemic of Zika virus (ZIKV), which was first detected in the country in May 2015. Since then, reports of microcephaly in the country have increased significantly, but a link between the virus and the birth defect has not been proven.
In the work published in Science, Patricia Garcez and colleagues examined the effects of Zika virus infection in human neural stem cells derived from induced pluripotent stem cells (iPSCs)—and growing as either clusters of neural stem cells (called neurospheres) or as brain organoids; both systems represent models with which to study embryonic brain development in vitro.
When the researchers infected the growing cells with Zika virus isolated from a Brazilian patient, the virus killed most of the neurospheres within a few days. Under control conditions, meanwhile, hundreds of neurospheres grew.
Confocal micrograph of human neural stem cell culture infected with Zika virus (red). Cell nuclei are shown in blue. Credit: Erick Loiola, Rodrigo Madeiro / IDOR
In a second experiment focused on the brain organoid model, infection with the virus reduced the growth of infected organoids by 40% compared to brain organoids under control conditions.
Finally, an experiment evaluating the impact of dengue virus, a flavivirus with similarities to ZIKV, showed a significant difference in cell viability after six days, with dengue-infected cells surviving much better. And brain organoids exposed to dengue virus showed no reduction in growth compared to controls.
The results, which suggest that the negative consequences of ZIKV in human neural stem cells are not a general feature of the flavivirus family, provide insights into ZIKV's possible effects on the developing brain.
Other studies are necessary to further characterize the consequences of ZIKV infection during different stages of fetal development, the authors say.
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Garcez PP et al. Zika virus impairs growth in human neurospheres and brain organoids. Science, Published April 10 2016. doi: 10.1126/science.aaf6116