New insights into how Zika causes microcephaly

Wellcome-funded researchers have uncovered why the Zika virus may specifically target neural stem cells in the brain. This helps to explain how Zika can cause microcephaly in babies.

Representation of the surface of Zika virus with protruding envelope glycoproteins.
Representation of the surface of Zika virus with protruding envelope glycoproteins, shown in red.
Credit: Kuhn and Rossmann research groups, Purdue University/EurekAlert

Since 2016, thousands of children across South America have been born with microcephaly, which causes abnormally small heads, after their mothers became infected with Zika.

Researchers believed that the virus was targeting stem cells in the developing brain, but did not know why or how.

In a study, published in Science, the team showed that the Zika virus hijacks a human protein called Musashi-1 (MSI1), which is present in large amounts in neural stem cells. MSI1 allows Zika virus to replicate inside these cells and kill them. Neural stem cells eventually develop into a baby’s brain, so any loss of these cells can prevent a normal-sized brain from growing.

"This is the first study to show a clear link between a specific protein, the Zika virus and microcephaly," says Dr Mike Turner, Wellcome's Head of Infection and Immunobiology. "This new finding really helps to explain why neural stem cells are so vulnerable to Zika infection and I hope this can be a first step in determining how we could stop this interaction and disease."

What the research found

The researchers showed that when Zika virus enters cells, it binds with the MSI1 protein. This allows the virus to replicate rapidly, making the stem cells vulnerable to virus-induced death.

Zika virus also prevents MSI1 from acting to regulate and maintain the pool of neural stem cells. By binding with MSI1, the protein can’t activate its usual targets within the cell, leading to a loss of neural stem cells. 

In both these scenarios, the stem cells, which are crucial for normal neural development, are lost, leading to microcephaly. 

More information

Read more about the research in our press release.

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