In one of the first studies that sheds light on exactly how Zika attacks, researcher Patricia Garcez of the Federal University of Rio de Janeiro took human neural stem cells and infected them with virus taken from a Brazilian patient. Neural stem cells -- which are able to turn into three major cell types that make up our central nervous system -- are the key players in embryonic brain formation.
Garcez and her colleagues used two models for their experiments. The first involved looking at what are known as neurospheres, which are clusters of neural stem cells. The second used brain organoids, which are often referred to as miniature brains growing in petri dishes, but are actually just bundles of human tissue that have some features of the early human brain in the first trimester.
The results were unlike those of other viruses the team had studied.
Under control conditions, the neurospheres flourished, with hundreds of them growing. But when they added Zika, the virus ended up killing most of the neurospheres within a few days. A similarly disturbing thing happened with the brain organoids. The infected organoids grew to only 40 percent of those that were not exposed to the virus.
The team concluded that it appears Zika "targets" human brain cells specifically.
The results, and some incredible images taken by electron microscope, were published in Science on Sunday night.
In this first set, picture A shows a normal control neurosphere. Notice the spherical shape. Picture B is infected with Zika and the shape has changed. Picture C shows a dish with hundreds of neurospheres while Picture D shows how few are left after Zika. The graphic, labeled E, quantifies the number of neurospheres in the control, "mock," and three dishes infected with Zika.
The next group of pictures shows more details about how the structure of neurospheres changed six days after being infected by Zika. Picture A shows a control neurosphere. Picture B shows an infected neurosphere with evidence of a nucleus undergoing necrosis and swollen mitochondria. Arrows point to "envelopes" of the virus on the cell surfaces. Pictures C-F are close-ups of parts of the infected cells.
The final pictures are of brain organoids. Picture A represents the control. Picture B shows a organoid which was infected at 35 days with Zika. Eleven days after being exposed to the virus, it's significantly smaller than the organoids that were not infected. Arrows point to cells that became detached from the organoids. The graphs, labeled C and D, show the difference size over time and E shows the quantification of the average difference between the two groups (control and infected).
The scientists also conducted the same study with dengue, which is from the same flavivirus family as Zika and is thought to share many characteristics with it. Not unsurprisingly given the fact that microcephaly has not been associated with dengue ,the neurospheres survived much better than when infected with Zika and the brain organoids showed no reduction in growth when compared to the controls.
In a separate but complementary study published in March in Cell Stem Cell, researchers from Johns Hopkins University, Florida State University and Emory University took human stem cells and exposed them to Zika. They found that within three days, the virus had selectively infected cells forming the brain's cortex, which is the thin outer layer of folded gray matter.
The studies add to the understanding of how the virus appears to be linked to the thousands of babies in Brazil who are being born with microcephaly, a condition marked by an abnormally small head and that appear to be accompanied by brain defects in many cases related to Zika.
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