A Common Virus May Be Linked To Heart Problems In Fetuses

January 22, 2021

A recent study has found that a common virus, which usually causes only mild symptoms in adults, may cause heart defects in developing human fetuses.

Previous research has suggested that the virus, known as Coxsackie virus B, may be linked to miscarriages early in pregnancy. But many questions remain about the specific threat the virus poses to the developing fetus. (Another form of the virus, known as Coxsackie virus A, causes hand-foot-and-mouth disease).

New findings presented last month at the annual meeting of the American Heart Association’s Scientific Sessions suggest that coxsackievirus B infection in pregnant women may be linked to heart defects in the fetus.

“Because it’s a common virus and it’s known to affect adults, [we think] it may be problematic at the fetal stage as well,” 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, symptoms of coxsackievirus B are usually mild, although in rare cases the infection has been linked to more serious symptoms, such as myocarditis, or inflammation of the heart muscles, Sharma noted.

To understand the effects on the fetus, the researchers started with mice.

In the first part of their study, they infected pregnant mice with a strain of the virus at different doses and at different points in fetal development related to human pregnancy.

They found that 60 percent of the fetuses of infected mice developed heart defects, the most common defect being a type of ventricular septal defect. In humans, this defect is one of the most common types and is characterized by a hole in the ventricular septum-the wall separating the left and right sides of the heart. The septum protects deoxygenated blood from mixing with oxygenated blood, but if the hole is large enough, mixing can occur and the body may not get enough oxygenated blood, Sharma told Live Science.

The team found that the timing of the infection was also important, with pregnant mice having the highest risk of developing heart defects if they were infected at a time that corresponded to “early pregnancy” in humans.

Coxsackie virus works by binding to the coxsackie-adenovirus receptor (CAR), which is found in high levels in the hearts and brains of mouse fetuses, Sharma said. And while the presence of this receptor allows the virus to freely infect humans, without it, studies have shown that mouse fetuses would not survive, Sharma said. It’s unclear what the receptor does in their bodies, he added, but it’s thought to be important for binding cells together during development.

Next, Sharma and his team looked at which genes were turned on or off after the mice were infected. They hypothesized that the virus causes heart defects by turning on genes that increase levels of proteins and weaken the ability of heart cells to reproduce and grow.

Still, the study was done in mice, and while Sharma believes that most of these results can be translated to humans, “humans are a little more complex than mice – obviously our mice are in a controlled environment, but humans, they’re not.” He said.

But to demonstrate that these mouse experiments may have clinical relevance, the researchers also studied humans.

For the second part of the experiment, the team recruited 270 pregnant women and collected blood samples at various times during their pregnancies to see if the women had antibodies to fight the virus in their blood. (The presence of antibodies would mean that the woman had been infected with the virus.) When the women gave birth, researchers found that those babies with heart defects also had elevated levels of these antibodies during pregnancy, Sharma said.

Dr. Ameesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security in Baltimore who was not involved in the study, said, “It makes biological sense that this virus could be linked to congenital heart disease.” That’s because the virus sometimes causes heart infections in children and adults, he said, and the receptor the virus needs is present in the fetal heart.

However, while mouse studies suggest a possible causal link, more data on humans is needed, Adalja told Live Science. because coxsackievirus is so common, many people may have antibodies against the virus in their blood. Researchers need more data on the levels of these antibodies and whether they’re more frequently found in pregnant women with children with birth defects than those without “to kind of try and prove that it’s actually causal,” he said.

Their work is ongoing, and Sharma says he hopes they’ll eventually be able to figure out more details behind the pathway from infection to heart defects in mice so they can try to find that pathway, if it exists, in humans. (For now, the study only shows an association between coxsackievirus B infection during pregnancy and fetal heart defects, not a cause-and-effect relationship.)

As for pregnant women, Sharma advises caution. For example, people can get this infection through contaminated food.” Wash your hands [before you eat], and if you eat [something], try to wash it well before you eat it – just be a little more hygienic,” says Sharma.