Blocking Zika Virus from the Placenta May Prevent Birth Defects

Scientists are zeroing in on how Zika invades the placenta to harm unborn babies. Learning how to block Zika from the placenta could prevent birth defects.

Zika is no longer labeled a global health emergency by the World Health Organization, but that doesn’t mean the mosquito-borne virus is no longer a serious threat — especially to unborn babies. Although most adults who are infected with Zika have mild symptoms, exposure to the virus before birth puts infants at risk for a host of Zika-caused birth defects, including vision problems and microcephaly, which is marked by abnormal brain development and smaller than normal head size.

As work continues on developing and testing vaccines to protect against Zika infection, figuring out how Zika specifically infects the unborn to cause birth defects is also a target of researchers. And a discovery about the tricky nature of the virus could hold a key to blocking Zika from damaging babies — even if moms-to-be are infected with the virus.

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It turns out Zika harms the developing fetus by invading the placenta, the organ that develops in the uterus during pregnancy and connects a mother and her developing fetus. Like all viruses, Zika infects the body by using a chemical reaction to get inside cells. If the exact chemical reaction enabling Zika to infect cells could be identified and stopped, it could keep the virus out of the placenta — and out of babies.

Robert Linhardt, PhD, a Rensselaer Polytechnic Institute chemistry professor, had a “light bulb” moment about this possibility when he learned about Zika’s insidious ability to damage unborn babies. In earlier research, Linhardt and his colleagues had discovered a virus related to Zika, dengue fever, enters cells by binding to glycosaminoglycans — long sugar carbohydrate chains found in numerous cells in the body.

"Based on the similarity between the two viruses, we thought that maybe Zika did the same thing,” Linhardt said.

To test the idea that sugar chains might be involved in Zika’s ability to infect babies through the placenta, Linhardt and graduate student So Young Kim mixed the protein envelope found on the outside of the Zika virus with glycosaminoglycans. They found the sugar reacted with Zika like it did with dengue. It was tightly bound with Zika’s protein coating, suggesting the virus gains entry to infect cells through glycosaminoglycans.

Next, the research team extracted sugars from various human tissues to see how tightly the Zika envelope protein hooked up with them. The result was a “hit.” The Zika protein latched on especially tightly to a form of glycosaminoglycan, chondroitin sulfate, found in the placenta.

This research, presented at the253rd National Meeting & Exposition of the American Chemical Society (ACA), while preliminary, opens the door to a new way of thinking about how unborn babies could be protected from Zika. And that’s important because, while vaccines are being researched and tested, including a National Institutes of Health trial of an experimental vaccine, there is also a need to find a way to protect unborn babies whose mothers may already be infected with Zika.

Linhardt’s team is researching ways to protect fetuses from Zika’s damage by blocking the interactions between the virus and placental sugars. For example, they are developing nanoparticles coated with the sugars to act like decoys that will attract and halt Zika infection in the placenta to prevent birth defects.

“I think the development of vaccines is going to be very complicated,” Linhardt said at the ACA press conference. “So that’s why we’re so excited about moving forward with, first, a better understanding of Zika and how it differs from dengue, and second, to try to develop new therapeutic approaches that could be helpful while a vaccine is developed.”

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