The evidence gets stronger every day that the Zika virus causes microcephaly. Now, a study has found a likely biological link between the mosquito-borne virus and the rare birth defect.
Since the Zika outbreak that started in Brazil last May, more than 5,000 babies have been born with abnormally small heads and the possibility of severe developmental delays.
Public health experts have been baffled by this outcome. The only known factor these babies have in common is that at some time during pregnancy, the mothers had the Zika virus. Research is underway to find other causes, but the World Health Organization said in February that Zika is guilty until proven innocent.
Since then, scientists have been trying to find out why and how the Zika virus affects the developing brain and when the fetus is most vulnerable.
Zika in the lab
At Johns Hopkins' Institute for Cell Engineering, part of Johns Hopkins Medicine, neuroscientists Hongjun Song and Guo-li Ming collaborated with virologist Hengli Tang at Florida State University and colleagues in a laboratory study to see if they could make the connection between the virus and the birth defect.
"In this study, we just asked a very simple question: What are the cells that [are] preferentially vulnerable for the Zika virus?" said Ming, one of the lead researchers.
The scientists took lab-grown neural stem cells and neural progenitor cells — the building blocks of the brain — and infected them with the Zika virus in culture dishes. Three days after the virus was applied, 85 percent of the cells were infected.
"What we found is there are two things the Zika virus can do: First, it will kill some of the neural stem cells that are responsible for forming part of the brain and, also, it will slow down the growth of the neural progenitor cells if they're not bad yet," Ming said.
Progenitor cells are like stem cells, only more specialized. A major difference between the two is that stem cells can reproduce indefinitely, while progenitor cells can divide only a limited number of times. That means a damaged progenitor cell might not be able to produce enough copies of itself to fix a problem.
Zhexing Wen, one of the researchers at Johns Hopkins, said the virus has an affinity for attacking neural progenitor cells as opposed to other cells. The researchers noted that the virus used the cell's ability to reproduce itself to make copies of the virus, which helped it spread to healthy cells.
Song's team also reported that the infected cells grew more slowly than healthy cells, and their division cycles were interrupted — factors that could also contribute to microcephaly.
A step toward understanding
While the researchers said their work does not prove conclusively that Zika causes microcephaly, they said it is an important step toward that goal.
And, although it might be logical to conclude from the study that the Zika virus attacks, damages and kills important cells that build the brain, Ming said they now have to "determine whether the Zika virus infection can lead to microcephaly in a different cultural model system, a three-dimensional model." That would be a more realistic experiment that would allow scientists to mimic the developing brain.
The scientists from both universities are collaborating on another study.
"We would like to see whether we can find ways to block the Zika entry or the action of the Zika virus on the cells," Ming said.
Blocking the virus, or preventing it from damaging the brain cells, would make the virus far less threatening than it is now.
Their work on the biological link between Zika and microcephaly has been published in Cell Stem Cell. The study was funded by Florida State University, the Maryland Stem Cell Research Fund, and the National Institutes of Health.