Three separate studies released Wednesday present the first batch of mouse model data on what happens when Zika virus infects a pregnant mammal—and the data is as grisly as one might expect.

The three studies were led by research groups in Brazil, the US, and China and back up the grim epidemiological data in humans, which links the virus to miscarriages and birth defects, particularly microcephaly, a defect in which babies are born with small and malformed brains.

Collectively, the new studies highlight that when Zika infects a pregnant mouse, the virus homes in on the developing fetuses, invading the placenta and fetal brains in large numbers. In one of the studies, viral numbers in the placenta were 1,000-fold higher than in maternal blood. Once in fetal brains, the virus specifically attacked developing and mature neurons, triggering cell death, haywire immune responses, and severe brain malformations. In another of the studies, researchers noted that the number of viruses in a fetal brain increased by about 300 percent within three days of invasion. Many of the pups in the studies died in utero, while others were quickly eaten by their mothers after birth—a common mouse response to birthing sickly pups.

While Zika’s ferociousness in the unborn is stunning, the mouse model data doesn't yet tell us new facts about the devastating virus, which is currently blazing through South and Central America. Rather than new insights, the excitement of the studies stems from the mouse models themselves. Now that researchers have worked out procedures to infect the rodents in a way that establishes infections and causes birth defects, researchers can copy the methods to ask new questions about the virus’ biology and test potential new therapies.

Getting to these models wasn’t easy; mice typically aren’t bothered much by viruses such as Zika, a member of a viral family called Flaviviruses that includes dengue and yellow fever. To establish infections in mice, the three research groups each came up with their own tricks.

The research group out of Beijing, China, ended up directly injecting an Asian strain of Zika directly into the brains of fetal mice in utero. The researchers performed the injection about midway through pregnancy—corresponding to the second trimester in human terms—because they found that earlier infections would simply kill off the pups. After the infection, the researchers monitored the pups, noting how virus numbers increased 300-fold in the first three days, ravaging developing neurons and shrinking brains. Their results appear in the journal Cell Stem Cell.

In another study published in Cell, researchers at Washington University in St. Louis established Zika infections in pregnant mice by shutting down the rodents’ immune systems in two different ways. First, the researchers genetically engineered mice to have defective type I interferon signaling, the body’s alarm system for viral infections. Infecting these pregnant mice with a French Polynesian strain of Zika ended up killing the fetuses in utero. In the second model, the researchers shut down type I interferon signaling using antibodies, which weakened but didn’t devastate immune responses. Fetuses in this model survived but still became infected with Zika in utero. The researchers watched as viral loads exploded in the placenta, crossed into fetal brains, and wreaked havoc on the unborn pups.

In the last study, published in Nature, researchers at the University of São Paulo injected a relatively high dose of a Brazilian strain of Zika virus into pregnant mice, establishing infections. The researchers also compared infections caused by the Brazilian strain with that of the African strain, isolated in Uganda in 1947. The researchers noted that the Brazilian strain seemed more aggressive and better at infecting fetal brain cells, suggesting adaptation from decades of swirling among human hosts. While the finding isn’t surprising (and may be exaggerated by the African strain’s long passage in labs, where it could have lost some of its potency), the finding raises more questions about how the virus has evolved to brutally attack fetal brain cells.

With these new models, researchers will begin to get answers to those questions, the authors of the Nature study said.

Cell Stem Cell, 2016. DOI:10.1016/j.stem.2016.04.017 (About DOIs).

Cell, 2016. DOI: 10.1016/j.cell.2016.05.008

Nature, 2016. DOI:10.1038/nature18296