How Zika Breaks Into the Brain

When Brazil’s alarming spike in newborns with brain damage was linked to an obscure virus last year, Arnold Kriegstein began to do some reading. Kriegstein, a neurobiologist at the University of California, San Francisco, learned that the Zika virus is named after the forest in Uganda where it was first discovered in 1947. Spread by mosquitoes, it causes fairly mild symptoms—a rash, inflamed eyes, muscle aches, a fever. But in late 2015, months after it appeared in Brazil, babies there began to be born with microcephaly, an underdeveloped brain, in surprisingly large numbers. In April 2016, the U.S. Centers for Disease Control and Prevention issued a statement: There was now enough evidence—especially the presence of the virus in the brains of stillborn infants—to suggest that Zika was the cause. But scientists knew next to nothing about how a virus could infect fetal brain cells and inhibit brain growth.

As Kriegstein read, he came across something that made him stop short. A 2015 paper revealed that the virus needed the presence of a receptor called AXL to infect certain cells. His lab had been studying stem cells found inside the developing brain, and he knew that AXL receptors coated these cells in a thick carpet. The receptor was also present in a limited number of other cells, including ones that make up the blood vessels heading into the brain and neural support cells like astrocytes and glia. “As soon we saw it, we were struck,” he said. They felt sure this was how the virus was getting in.

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Now, in a paper available as a preprint before peer review, Kriegstein’s lab and two others at UCSF describe experiments using human tissue that suggest the AXL receptor is at least part of how Zika manages to infect neural stem cells. They also investigated whether certain drugs could keep the virus from replicating in infected cells, detailing promising early results of a common, pregnancy-safe antibiotic called azithromycin.

These are just some of the findings pouring out of dozens, if not hundreds, of collaborations focused on the virus and its effects. This spring and summer, study results have converged on the fact that neural stem cells—cells that will eventually develop into neurons and other cell types—are susceptible to Zika infection, while mature neurons are not so vulnerable. Other findings focus on what exactly Zika is doing once it gets inside those cells, where it seems to be keeping the cells from growing, dividing and developing. Another pressing question is how the placenta, a tissue with such a remarkable ability to withstand infection that only a small number of pathogens are known to cross from the mother to the fetus, lets Zika through. And why do some babies born to Zika-infected mothers suffer from microcephaly, others from retinal deformities, while others have no apparent damage? Questions abound; answers are only beginning to take shape.

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