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How the Zika virus is probably causing birth defects in children

It may be changing how brain cells express genes

Strong evidence suggests the mosquito-borne Zika virus is causing infants to be born with birth defects — and a lab model provides clues on how it happens. The virus is capable of infecting the cells that form the brain's outer layer, making them more susceptible to death and preventing them from forming new tissue. Though this study took place in a lab dish, rather than in a human person, it may explain how Zika stunts brain development.

The virus is capable of infecting the cells that form the brain's outer layer

The findings come from a new study published in Cell Stem Cell that looked at how the Zika virus interacted with human stem cells grown in a lab. The stem cells were made to mimic the types of cells that eventually form the cortex — the brain's outer layer. Within three days of being exposed to Zika, up to 90 percent of these cells had been infected. Not only did this lead to massive cell death, but the infected cells were reprogrammed to produce even more copies of the Zika virus. These experiments could eventually help doctors find new drugs to stop the virus' damage on unborn babies, the study authors argue.

The study is the first to show how Zika may be causing children to be born with abnormally small heads — a condition known as microcephaly. Researchers strongly suspect that the two conditions may be linked, due to the recent spread of both in Central and South America. Since March of last year, up to 1.5 million people in Brazil alone have been infected with the virus, according to the World Health Organization. The outbreak has coincided with a massive spike in cases of microcephaly in Brazil. Zika has also been found in the brains of developing fetuses, indicating that the virus can be transmitted from mother to child.

Today's research still does not confirm that Zika is causing these birth defects. The researchers only looked at how the virus interacts with individual brain cells in a lab setting, indicating which cells may be susceptible to the virus. To truly confirm Zika is behind microcephaly, the researchers would need to observe how Zika damages the entire brain. "Maybe the next step will be to use Zika on a 3D mini-brain to look at a more direct link," said one of the study authors Zhexing Wen, a neurobiologist at Johns Hopkins University School of Medicine.

This image shows cell death of the stem cells in red; the ZIKA virus is highlighted green. (Sarah C. Ogden)

But the study did reveal the extent to which Zika may be damaging the developing brain's cells. When Zika was introduced into a plate of stem cells, the virus altered how the cells' genes were expressed, reprogramming the cells to become mini Zika-producing factories. The virus also seemed to turn off the genes needed to fight off viral infection, causing many of the stem cells to die. And the genes that govern cell division were disrupted as well, indicating that the cells couldn’t divide to form new brain tissue.

There are still many unknowns about Zika's role on the developing fetus

Even if these experiments don’t confirm a direct Zika-microcephaly link, they could be used to screen for drugs that stop Zika from harming the brain, according to Wen. Researchers could add different compounds to the stem cells when they are exposed to Zika, to see which drugs work best at preventing infection or cell death.

Yet there are still many unknowns about Zika's role on the developing fetus that need to be answered, according to Sika Zheng, an assistant professor of biomedical sciences at University of California, Riverside, who was not involved in the study. It’s still unclear if Zika is harming the brain itself, or if it’s causing fevers and other symptoms in the mother that are indirectly damaging the baby's brain. And if Zika is directly harming the brain, how is it crossing the blood-brain barrier? "The single most important evidence is looking to see if this virus can get into the brain [in a living patient]," said Zheng.