Richard T. Ellison III, MD reviewing Tang H et al. Cell Stem Cell 2016 Mar 4. Garcez PP et al. Science 2016 Apr 10.
Two studies show that the Zika virus impairs the growth of human neural progenitor cells.
A major global public health question is whether the newly emerged flavivirus, the Zika virus (ZIKV), causes microcephaly (NEJM JW Infect Dis 2016 Apr 20 and N Engl J Med 2016 Apr 13; [e-pub]). Two new studies provide in vitro evidence that ZIKV can both infect human neural progenitor cells and affect their growth.
Tang and colleagues studied the ability of a ZIKV isolate to infect various human cell lines. They found that ZIKV could infect human neural progenitor cells (hNPCs) derived from human induced pluripotent stem cells, with infection spreading to 65% to 90% of hNPCs in cell culture within 3 days. Compared with mock exposure, infection with ZIKV led to an approximate 30% reduction in hNPCs within 66 to 72 hours. ZIKV-infected cells had higher caspase-3 activation (which is associated with apoptosis) and signs of cell-cycle dysregulation.
Garcez and colleagues similarly tested the ability of ZIKV to infect human pluripotent stem cells that had been induced to become neural stem cells, neurospheres, or brain organoids. They also found that ZIKV readily infected stem cells. In addition, whereas mock-infected stem cells generated hundreds of round neurospheres in 6 days, ZIKV-infected cells generated only a few morphologically abnormal neurospheres and had apoptotic changes. In studies with brain organoids, ZIKV infection led to a 40% reduction in the 11-day in vitro growth rate. In comparative studies, the related flavivirus dengue virus 2 infected neural stem cells but did not induce caspase 3/7–mediated cell death (whereas ZIKV did), and did not affect the development of neurospheres or the growth of brain organoids.
Citation(s):
Tang H et al. Zika virus infects human cortical neural progenitors and attenuates their growth. Cell Stem Cell 2016 Mar 4; [e-pub].
Garcez PP et al. Zika virus impairs growth in human neurospheres and brain organoids. Science 2016 Apr 10; [e-pub].
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