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But, health experts have been at a loss to say whether or how the virus might cause the birth defect.
Now, laboratory studies have shown that Zika can infect a type of neural stem cell that gives rise to the cerebral cortex of the brain, researchers report in the March 4 issue of the journal Cell Stem Cell.
"Although our study hasn't provided a direct link between Zika virus and microcephaly, we identify the direct cell targets of the virus and we show the virus can affect cell growth," said study co-author Zhexing Wen, a postdoctoral fellow at the Johns Hopkins University School of Medicine in Baltimore.
Since the Zika epidemic began, there have been more than 5,600 suspected or confirmed cases of microcephaly in Brazil, the World Health Organization has reported.
The new findings "provide a potential mechanism [for] how a Zika virus infection can lead to poor brain growth and, therefore, microcephaly," said Dr. Sallie Permar, director of Duke University's Laboratory of Neonatal Viral Pathogen Immunity, in Durham, N.C.
The researchers said the stem cells targeted by Zika are called cortical neural precursors, and they spawn the brain cells that make up the cerebral cortex, the outer layer of the brain's gray matter that's largely responsible for higher brain functions.
The researchers tested Zika's effect on these cells using a Zika virus stock grown in mosquito cells, to replicate the means by which the virus infects human beings.
The virus was able to spread rapidly through these stem cells, the researchers learned. In as few as three days following exposure to the virus, 90 percent of the cortical neural precursor cells in a lab dish had become infected.
Worse, Zika appears to hijack these cells, using them to churn out new copies of the virus and spread more rapidly, the researchers reported.
Many of the infected cells died, and others showed disruption that could limit their ability to divide and flourish.
Wen said their findings are a "first step" that provide an "entrance point" to seeking further answers on ways to combat the Zika virus and, hopefully, microcephaly.
"The more we understand about the central effects of Zika virus on the fetus, that will help us in understanding how we can better combat the potential fetal effects of the virus," Permar said.
This is the sort of research that helped doctors understand and combat other infections that cause birth defects, she said.
For example, studies of cytomegalovirus infection during pregnancy -- which can lead to movement problems and well as deafness and blindness -- have led to many advances that either prevent or limit the effect of the virus on developing fetuses and babies, she said.
"Over time we learned that antiviral treatment at birth can help prevent some of the long-term developmental effects of congenital cytomegalovirus," Permar said.
The researchers behind the new study said they're now using the cells to find out more about the effects of Zika infection on the developing cortex.
"Now that we know cortical neural progenitor cells are the vulnerable cells, they can likely also be used to quickly screen potential new therapies for effectiveness," said Hongjun Song, a professor of neurology and neuroscience at Johns Hopkins' Institute for Cell Engineering.
The research was carried out by scientists at Johns Hopkins University School of Medicine, Florida State University and Emory University.
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