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Mouse Models Reveal How Zika Infects Fetuses

Virus attacks placenta first, then fetus, study shows

WEDNESDAY, May 11, 2016 (HealthDay News) -- Scientists have created the first model of how the Zika virus spreads from a pregnant mouse to its fetus.

The mouse model showed that the virus first damages the placenta before infecting the fetus, causing many of the same complications seen in human babies.

"There have been questions regarding whether in utero transmission of Zika virus actually causes disease in the fetus. While the evidence has been mounting, our data confirms that Zika virus can cause congenital problems, including fetal death," Michael Diamond, a viral immunologist at Washington University in St. Louis, said in a university news release.

Mice aren't normally vulnerable to Zika virus. For the study, the researchers created two mouse models to show how Zika infects a fetus. The first involved genetically modifying the immune system of females. In the second model, genetically normal female mice received injections of an antibody that impaired their immune system.

Once the genetically modified pregnant mice were infected with Zika virus, the researchers were able to observe the transmission of the virus to the mouse fetus. The virus zeroed in on the placenta, creating viral levels 1,000 times higher in the placenta than in the mother's blood, the researchers said.

Once in the placenta, the virus moved on and damaged the fetal blood capillaries. After the virus is in circulation, it is able to infect the fetal brain, the investigators found.

The study authors reported that many of the genetically modified mice miscarried. The fetuses that made it to term were much smaller and had Zika virus in their brains and central nervous system.

"Most of the time, the placenta is an effective barrier between the mother and her fetus," said the study's co-senior author, Indira Mysorekar, a reproductive biologist. "But Zika is able to overcome it."

It's important to note, however, that research done in animals doesn't always replicate what happens in humans.

The researchers are continuing their investigation to learn exactly how Zika crosses the placenta and identify other complications among infected mouse fetuses.

"The two models provide different aspects of the biology," said Diamond. "In the knockout model, we see the growth retardation, fetal demise and injury to the brain. In the blocking-antibody model, which is less severe, we can follow the development of the mice after birth. We plan to test them for any developmental changes that a milder Zika virus infection could have caused."

The study was published May 11 in the journal Cell.

More information

The U.S. Centers for Disease Control and Prevention has more about Zika and pregnancy.

SOURCE: Cell, news release, May 11, 2016

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