Lab-grown ‘mini brains’ reveal how Zika virus takes its toll

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A team of researchers has discovered how the Zika virus stunts head and brain development, thanks to sophisticated “mini-brains.” Studying a new type of pinhead-size, lab-grown brain made with technology first suggested by three high school students, Johns Hopkins researchers have confirmed a key way in which Zika virus causes microcephaly and other damage in fetal brains: by infecting specialized stem cells that build its outer layer, the cortex.

Researcher Hongjun Song said, “This more realistic, 3-D model confirms what we suspected based on what we saw in a two-dimensional cell culture: that Zika causes microcephaly, abnormally small brains and heads, mainly by attacking the neural progenitor cells that build the brain and turning them into virus factories.”

Song’s wife and research partner, Guo-li Ming, said, “One thing the mini-brains allowed us to do was to model the effects of Zika virus exposure during different stages of pregnancy.”

Ming added, “If infection occurred very early in development, the virus mostly infected the mini-brains’ neural progenitor cells, and the effects were very severe. After a while, the mini-brains would stop growing and disintegrate. At a later stage, mimicking the second trimester, Zika still preferentially infected neural progenitor cells, but it also affected some neurons. Growth was slower, and the cortex was thinner than in noninfected brains.”

These different effects correspond to what clinicians have seen in infants born to women who contracted Zika during pregnancy, as well as miscarriages, she notes, namely that the earlier in pregnancy Zika infection occurs, the more severe its effects.

The research group’s next step will be to test drugs already FDA-approved for other conditions on the mini-brains to see whether one might provide some protection against Zika.

The research appears online in the journal Cell.

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