When scientists discovered that the Zika virus was causing birth defects, it seemed to catch the world off guard. The mosquito-borne virus could slip from mother to fetus and damage the developing brain, leaving newborns with a range of serious complications.
But what if other viruses spread by insects also pose a threat to fetuses?
On Wednesday, scientists reported that two viruses, West Nile and Powassan, attacked mouse fetuses when pregnant mice were infected, killing about half of them. The viruses also successfully infected human placental tissue in lab experiments, an indication that the viruses may be able to breach the placental barrier that keeps many maternal infections from reaching the fetus.
Just because a virus proves fatal to a mouse fetus or replicates in human tissue in the lab does not mean that it causes pregnancy complications or birth defects in people, the scientists were quick to say. But Dr. Jonathan Miner, the senior author of the study, which was published in the journal Science Translational Medicine, said the results called for further research into these and other emerging viruses, and for experts to keep an eye out for possible complications when pregnant women acquire these infections.
“The last thing I want to do is create alarm and panic,” said Miner, an assistant professor at Washington University School of Medicine. “Our study does not demonstrate what happens in humans. That’s one reason why epidemiological studies in humans are so important, to show what’s really happening.”
West Nile virus has been circulating in the United States for two decades, so any spate of babies born with defects as a result would presumably have been noticed. But Miner and outside experts said that perhaps birth complications from West Nile are so infrequent — if they do occur at all — that no one would think to tie them to the virus unless they were aware of the possibility.
“Is it that we’re not looking hard enough for these things, or is it not there?” said Daniel Streblow, an associate professor at Oregon Health and Science University’s Vaccine and Gene Therapy Institute, who was not involved with the study. “Those are two valid points.”
Zika, after all, was first documented in 1947, but it was only in 2015 when authorities in Brazil first started noticing babies being born with Zika-linked microcephaly. Scientists have speculated that the virus mutated or that the population in Latin America was particularly vulnerable to infections. But perhaps it was that the connection between Zika and birth defects was noticed only because the outbreak of the virus was so massive — far wider than has been the case with West Nile.
There have been about 50,000 documented cases of West Nile in the United States in the past 17 years, and only about 100 cases of Powassan virus over the past decade.
“Maybe the reason we noticed Zika was because so many people were affected all at once,” said Dr. Desiree LaBeaud, an associate professor of pediatric infectious diseases at Stanford. “You need a really large outbreak sometimes to see rare complications.”
Miner and his colleagues at Washington University in St. Louis were among the many scientists who jumped into Zika research during the Latin American outbreak. As they combed through the literature about Zika and other flaviviruses, they discovered studies showing that other viruses were able to cause congenital infections in mice and even some case reports of infection spreading from mother to fetus in people, in what’s called vertical transmission.
One study, for example, found that of the 77 pregnant women infected with West Nile during an outbreak in 2003 and 2004, four had miscarriages and three had children with defects that researchers said could theoretically have been caused by congenital infections. There were not enough cases for experts to draw conclusions about the virus then, but it made Miner wonder if Zika was unique after all in its ability to affect pregnancies.
For the new study, the researchers infected pregnant mice with West Nile and Powassan, two flaviviruses that are transmitted to people by mosquitoes and ticks, respectively. The viruses were able to march across the placentas and reach the fetuses, causing severe damage to the developing nervous systems and leading to what scientists call “fetal demise” in half of them.
They then tested the viruses on human cells that make up different layers of the placenta, finding that West Nile was able to replicate in them about as proficiently as Zika, with Powassan infecting the tissue almost as efficiently.
“I do not think that placental infection means that the fetus definitely could be infected,” Miner said. “But if a virus is able to replicate in all three layers of the placenta, I think that means that the virus could be much more likely to cross the placenta” and affect the fetus.
The scientists ran the same experiments with two other viruses, chikungunya and Mayaro, which are alphaviruses, not flaviviruses. The viruses did not harm the mouse fetuses and there was little to no replication of them in the human placental tissue, meaning they likely don’t harm human fetuses. (Case reports have indicated that chikungunya can pass from mother to baby, but researchers think that the transmission happens as the baby travels through the birth canal, not across the placenta.)
Miner and outside researchers said it makes certain sense that West Nile and Powassan might be able to cause fetal infections and damage the nervous system. Not only are they flaviviruses like Zika, they are also neurotropic, meaning they target the nervous system. But the experts said they wanted to see results from studies in monkeys — which are much more similar to people than mice — before being convinced that these viruses pose a threat to fetal health.
Still, they said clinicians and epidemiologists should study birth outcomes during West Nile outbreaks.
“We have to be more vigilant now with West Nile outbreaks and actually monitor pregnant women more closely,” said Dr. Karin Nielsen, a pediatric infectious diseases expert at UCLA, who was not involved with the study.
Beyond the implications for West Nile, the paper outlines methods to study the potential of viruses to damage fetuses. Given that researchers can’t predict which virus to going to cause an outbreak next, they need tools like this to respond quickly during the next health crisis, experts said.
“One of the things in the whole viral field is that we’re trying to learn from existing viruses to get ahead of the next virus,” said Dr. Yoel Sadovsky, the executive director of the Magee-Womens Research Institute, who was not involved with the study. “Could we be better prepared when we face the next viral epidemic?”