- Infection of pregnant women with Zika virus is known to cause serious neurological problems in infants.
- New study states that Zika crosses the placenta and leads to a high percentage of miscarriages.
- In babies carried to term, it causes thinning of brain tissue and inflammation of the cells.
In mice with complete immune systems, Zika virus can cross the placental barriers in early pregnancies and lead to a high percentage of miscarriages and lead to birth of babies with thin brain tissue and inflammation in brain cells.
The findings are by researchers from Johns Hopkins University Bloomberg School of Public Health.
Placenta forms a barrier preventing toxins, bacteria and viruses from crossing and reaching the fetus. But by administering Zika virus directly into the reproductive tract of pregnant mice that have an intact immune system, the researchers found that the Zika virus appears to create disorganization in the cellular layers of the placenta.
Zika was considered a public health emergency by the World Health Organization and there is no current cure for it. Exposure of pregnant women with Zika, in early pregnancy, leads to serious neurological problems in infants.
"We need to find a way to stop transmission of Zika through the placenta into the fetus, because that is where the damage is being done," says study co-leader Sabra L. Klein, PhD, an immunologist and microbiologist at the Johns Hopkins Bloomberg School of Public Health. "In the placentas of our mice, we're seeing a defense against Zika being mounted, but falling short, especially in early pregnancy, a time that corresponds to the first trimester in humans."
Study co-leader Irina Burd, MD, PhD, a maternal/fetal medicine physician at Johns Hopkins Medicine, said "If we can determine what is happening, we may be able to find ways to minimize or even eliminate what can be devastating consequences for children of infected mothers," she says.
Study in Mice
For their research, the scientists developed a new mouse model that have completely intact immune systems more similar to humans.
This will enable researchers to understand the mechanisms behind Zika transmission to the fetus and to understand the processes involved in mounting an immune response.
To conduct this study, the researchers injected Zika virus directly into the reproductive tract of the pregnant mice during the stage that was considered equivalent to the first trimester in a human.
The researchers used several different strains of the virus, including the older strains from an outbreak in Nigeria in 1968 and Cambodia in 2010 and contemporary strains from Brazil and Puerto Rico from the most recent epidemics.
The results showed that nearly 94% of all pregnancies remained viable when a mock infection was introduced during the first trimester, while the viability of fetuses after Zika infection was reduced.
Viability ranged from 56% from infection with the Brazil strain to 71% following infection with the Nigeria strain. That means anywhere from 29% to 44% of pregnancies were lost following infection.
When the researchers infected the mice in the equivalent of the late second trimester, fewer miscarriages occurred, suggesting that vulnerability to Zika decreases later in pregnancy.
The researchers could also see the activation of antiviral defenses in the placentas of pregnant mice infected with virus.
Viruses cause infection by use of the lock and key mechanism to attach to specific receptors on host cells to take hold and spread.
Placental cells have receptors that the viruses can use to cause and spread infection.
These anti-viral pathways could be potential targets for treatments that could stop transmission, the researchers say.
The placenta is organized into discrete layers of tissue. But the researchers found that the layers of tissue in the placentas of the mice infected with Zika virus were no longer organized well and might be how the virus could penetrate the fetus.
"This could be why the fetuses in the Zika-infected mice were so vulnerable to either miscarriage or brain damage," Burd says.
The virus appeared to cross into the placenta easily during the first trimester, but not during the second and third trimester.
Similar to humans, the direct effects Zika infection on the pregnancy were much less pronounced if the infection occurred later in pregnancy.
Also, the mouse pups born to mothers after an early infection were likely to have thinner cortexes and have inflammatory cells in the brain, compared to those born after a later infection.
The researchers want to examine if the siblings of the babies born during Zika infection will also suffer neurological effects, in future.
"We don't know if the effects persist in future pregnancies," Klein says. "We're just dealing with the here and now. We have no idea what the long-term consequences are for the mother."
These findings are published in Nature Communications.
- Meghan S. Vermillion et al. Intrauterine Zika virus infection of pregnancy immunocompetent mice models transplacental transmission and adverse perinatal outcome. Nature Communications; (2017)