This post has been updated.
A team of U.S. researchers announced Friday that they believe they have discovered a mechanism for how the Zika virus can cause the rare birth defect known as microcephaly, in which babies are born with abnormally small heads and underdeveloped brains.
Working with lab-grown human stem cells, scientists found that the virus selectively infected cells forming the brain's cortex, the thin outer layer of folded gray matter. Its assault made those cells more likely to die and less likely to divide normally and make new brain cells.
The finding by researchers from Johns Hopkins University, Florida State University and Emory University offers among the strongest evidence yet of how Zika is harming fetuses. Health authorities are increasingly convinced that the mosquito-borne virus has caused microcephaly in hundreds of babies in Brazil, the epicenter of the Zika outbreak that is sweeping through the Americas.
"It strengthens the case that Zika is a culprit behind microcephaly," said Joseph Gleeson, an investigator for the Howard Hughes Medical Institute, who was not involved in the study. "It's a very important piece in the puzzle."
Researchers have already documented an increase of microcephaly cases coinciding with the outbreak and have found evidence of the virus in brains of newborns who died, as well as in fluid from the placenta of infected pregnant women.
But one of the missing pieces has been information about how Zika can slow or halt brain development in an unborn child. While Friday's study doesn't definitively prove that the disease causes microcephaly, it strengthens the link between the two by showing cells from the brain's cortex are vulnerable to attack from the virus, according to Guo-li Ming, a Johns Hopkins neurologist and one of the lead authors. Studies of fetuses and babies with the signs of microcephaly have found abnormalities in the cortex, Ming said.
"What we show is the first piece of evidence" consistent with the hypothesis that Zika infections cause microcephaly, said Hengli Tang, a virologist at Florida State University and another lead author. "We're literally the first people in the world to know this, to know that this virus can infect these very important cells and interfere with their function."
The study, published in the academic journal Cell Stem Cell, answers a key question about the viral path of attack, said Kristen Brennand, a stem cell biologist at the Icahn School of Medicine at Mount Sinai Medical Center in New York.
The researchers took human stem cells, exposed them to a strain of Zika and found that within three days, the virus had attacked specific kinds of cells critical to development of the brain's cortex. These cells became infected and also were hijacked to make new copies of the virus. Many died; others were damaged and unable to replicate.
The study doesn't address whether the virus can reach the brain cells. What it does show, Tang said in a conference call with reporters, is that if the virus is in the brain, "this virus can do a lot of damage."
Researchers used the original Zika strain, first discovered in Uganda in 1947. That strain is 89 percent identical to the current strain that has spread rapidly to about three dozen countries and territories, primarily in the Americas.
The authors and other experts noted that the study, which involved dozens of scientists working around the clock at four labs at three universities, still only goes so far and must be followed with additional research. It took place in a controlled environment, with lab-grown stem cells.
But Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, said its findings offer "potentially important" new information about the link between Zika and microcephaly.
"This paper points to a mechanism that's plausible and makes sense," Hotez said. "It gives us a clue as to why the virus inhibits the brain growth of a fetus. ... It adds an important brick in the wall that says Zika is the cause of this epidemic of microcephaly we're seeing. These kinds of studies can help melt away all the other theories."
Researchers said studies are still needed to definitively prove the link between Zika and microcephaly. The Centers for Disease Control and Prevention is currently working with a large population of patients in Brazil and scientists hope that will provide statistically significant clinical data to show the connection. Scientists could also infect animal models, such as mice, with the virus to get a better understanding of how the pathogen affects the neural system.