A new study that examines the effect of the Zika virus in two lab models of embryonic brain development offers evidence for how the virus may cause brain defects in babies.

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The researchers modeled early brain development from cultured neural stem cells (nuclei in blue) that they had infected with Zika virus (blue).
Image credit: Erick Loiola and Rodrigo Madeiro / IDOR

The researchers, from the D’Or Institute for Research and Education (IDOR) and the Federal University of Rio de Janeiro (UFRJ), both in Brazil, report their findings in the journal Science.

Brazil is in the midst of a Zika virus epidemic that coincides with a surge in the number of babies born with microcephaly – a rare birth defect where the brain fails to grow properly.

However, proof that Zika directly causes defects in fetal brains needs further confirmation, note the authors.

In their study, Patricia Garcez, adjunct professor in the Institute of Biomedical Sciences at UFRJ, and colleagues coaxed human-induced pluripotent stem cells (hiPSCs) into neural stem cells – precursor cells that go on to produce different kinds of brain cell.

They infected the neural stem cells with Zika virus isolated from a patient in Brazil.

Then, using techniques like immunocytochemistry and electron microscopy, they observed what happened as the cells grew into two 3D structures: neurospheres and brain organoids.

Neurospheres are clusters of neural stem cells, and organoids are lab-grown “mini-brains.” They are useful lab models for studying fetal brain development: neurospheres model some of the very early stages of brain cell growth, and organoids model the orchestration of cellular and molecular events that take place during fetal brain growth in the first trimester.

The team saw that the virus killed most of the neurospheres within a few days. Meanwhile, a control batch of neural stem cells produced hundreds of neurospheres over the same period. In the other model, infection with Zika virus reduced the growth of organoids by 40%, compared with uninfected control organoids.

Zika is a flavivirus that shares many similarities with dengue, another flavivirus. In a final experiment, the team compared Zika to dengue in the two lab models of brain development. Dengue-infected neurospheres survived much better than Zika-infected ones, and exposure to dengue did not impair organoid growth.

The researchers say their findings suggest the effect of the Zika virus on human neural stem cells is unlikely to be shared with other members of the flavivirus family and offer valuable clues about how the virus influences the development of the fetal brain in the first trimester.

They call for further studies to examine the effect of Zika virus on brain development during the other stages of pregnancy, as they conclude:

Our results, together with recent reports showing brain calcification in microcephalic fetuses and newborns infected with ZIKV [Zika virus], reinforce the growing body of evidence connecting congenital ZIKV outbreak to the increased number of reports of brain malformations in Brazil.”

Meanwhile, Medical News Today brings news of another new study that suggests Zika virus is linked to another brain disorder called acute disseminated encephalomyelitis (ADEM).