The Zika virus made headlines worldwide over the last few years, though news on its outbreak has slowed down in recent months. Zika is transmitted via mosquitoes and sexual contact, and it causes flu-like fever and aches. It's a particularly worrying disease because it causes microcephaly in babies if their mothers contract Zika while pregnant.

This occurs because Zika has the ability to cross the placental barrier, even though other related viruses cannot. A recent study published in PNAS describes the mechanism that this virus may be using to cross this barrier—Zika is able to infect the cells that line blood vessel walls, which are a major part of the placenta. The research also identifies the protein on the cells' surface that Zika latches onto, a revelation that provides avenues for developing potential treatments.

Zika is part of a genus of viruses known as the flaviviruses; other members of this group include Dengue and West Nile. All of these can cause serious health consequences, but only Zika causes microcephaly in the fetuses of infected mothers. Fetuses aren’t afflicted by many maternal infections, because the placenta provides a barrier that many pathogens are unable to cross. The placenta is an effective barrier because it separates the maternal blood from the fetus’, using tissue that is partially made up of fetal endothelial cells, which line the blood vessels on the fetal side of the barrier.

The authors of this paper were interested in how flaviviruses interacted with these fetal endothelial cells. They began by culturing human umbilical endothelial cells in a petri dish and then added some Zika, Dengue, or West Nile virus. Zika was able to infect these cells while Dengue and West Nile could not.

The researchers checked the fetal cells for expression of a variety of proteins flaviviruses use to latch on to cells. A protein called AXL was the only one that was present. The researchers went on to show that antibodies that bind to the AXL protein prevented Zika from entering cells. These antibodies had no effect on Dengue and West Nile viruses when they were used to infect other cell types. The antibodies also had no effect on other viruses that can cross the placental barrier, like influenza.

The authors note that though their study didn’t find AXL-dependent infection for other flaviviruses (Dengue and West Nile), previous studies showed that these viruses bound to AXL. They suggest that this discrepancy may be because studies sometimes use different types of cells to cultivate the viruses; it's possible that this kind of experimental variation could lead to different findings.

Knowing which protein participates in Zika’s binding to endothelial cells provides scientists with additional targets for future antiviral therapies. Moving forward, more research is needed on the interaction of the Zika virus with the AXL receptor, so we can learn whether it can be blocked without altering AXL's normal function.

PNAS, 2017. DOI: 10.1073/pnas.1620558114 (About DOIs)