A common virus that typically causes only mild symptoms in adults might lead to heart defects in developing human fetuses, a recent study finds.
Previous research has suggested that the virus, called coxsackievirus B, may be linked to miscarriages in early pregnancy. But many questions remained about the specific threat the virus poses to developing fetuses. (Another form of the virus, called coxsackievirus A, causes hand, foot and mouth disease).
The new findings, presented last month at the American Heart Association’s Scientific Sessions annual meeting, suggest that coxsackievirus B infection in pregnant women may be linked with heart defects in fetuses.
“Because it’s such a common virus and it’s known to have effects on adults, [we thought] it could be problematic in fetal stages, too,” said lead study author Vipul Sharma, a postdoctoral fellow in the department of surgery at Washington University School of Medicine in St. Louis. (In adults, coxsackievirus B symptoms are typically mild, though in rare cases the infection has been linked to more severe symptoms, such as myocarditis, or inflammation of the heart muscles, Sharma noted.)
To learn about the effects in fetuses, the researchers started in mice.
In the first part of their study, they infected pregnant mice with one strain of the virus at different doses and at different points in fetal development correlating to human pregnancy. [9 Uncommon Conditions That Pregnancy May Bring]
They found that 60 percent of the infected mice had fetuses that developed a heart defect, the most common defect being a form of ventricular septal defect. In humans, this defect is among the most common types, and it is characterized by a hole in the septum — the wall that separates the left side of the heart from the right. The septum protects deoxygenated blood from mixing with oxygenated blood, but if the hole is big enough, mixing occurs, and the body may not get enough oxygenated blood, Sharma told
The team found that the timing of infection was also important, and the risk of developing heart defects was highest if the pregnant mice were infected at a time corresponding to “early pregnancy” in humans.
The coxsackievirus works by binding to the Coxsackie-Adenovirus Receptor (CAR), which is found at high levels in mice fetuses’ hearts and brains, Sharma said. And though the presence of this receptor gives the virus free reign to infect the body, without it, studies have shown that mouse fetuses don’t survive, Sharma said. It’s unclear what this receptor does in their bodies, but it’s thought to be important for binding cells together in development, he added.
Next, Sharma and his team looked at which genes were turned on or off following the infection in mice. They hypothesized that the virus leads to heart defects by turning on genes that increase levels of proteins that diminish the ability of heart cells to multiply and grow.
Still, this research was done in mice, and though Sharma thinks much of these results could be translated to humans, “humans are a bit more complex than mice — and obviously, our mice are in a controlled environment, but humans, they are not,” he said.
But to show that these mouse experiments could have a clinical significance, the researchers also looked at humans.
In the second part of the experiment, the team recruited 270 pregnant women and took blood samples at various times of their pregnancy to see if the women had antibodies to fight the virus in their blood. (The presence of antibodies would mean that the woman had had an infection with the virus.) When the women gave birth, the researchers found that those who had babies with heart defects also had elevated levels of these antibodies during their pregnancy, Sharma said.
Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore, who was not involved in the study, said that “it makes a lot of biological sense that this virus could be involved in congenital heart disease.” That’s because the virus sometimes causes heart infections in children and adults, and the receptor that the virus needs is present in the fetal heart, he said.
However, although the mouse study suggests a possible cause-and-effect relationship, more data is needed on humans, Adalja told Because coxsackieviruses are so common, a lot of people probably have antibodies against the viruses in their blood. Researchers need more data on the levels of these antibodies and whether they appear more frequently in pregnant women who have children with birth defects than those who don’t “to kind of try and prove that this is actually causitive,” he said.
Their work is ongoing, and Sharma said that he hopes they can eventually figure out more details of the mechanism behind the pathway that leads from infection to heart defects in mice, so that they can then try to find this pathway (if it exists) in humans. (Currently, the findings only show an association between coxsackievirus B infection during pregnancy and heart defects in fetuses; they do not show cause and effect.)
As for pregnant women, Sharma recommends caution. People can get this infection through contaminated food, for example. “Wash your hands [before eating], and if you eat [something], try to wash it before you eat properly — just be a little bit more aware of your hygiene,” Sharma said.
The findings have not yet been published in a peer-reviewed journal.