West Nile linked to birth defects in fetal mice

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Two viruses closely related to Zika—West Nile and Powassan—can spread from an infected pregnant mouse to her fetuses, causing brain damage and fetal death, a new study suggests.

The findings suggest that Zika may not be unique in its ability to cause miscarriages and birth defects.

“We only studied mice and human tissues, so we can’t say for sure what happens when pregnant women are infected with these viruses,” says Jonathan Miner, an assistant professor of medicine at Washington University in St. Louis and senior author of the study, which appears in Science Translational Medicine. “But our findings suggest that it is possible that viruses related to Zika, such as West Nile, pose the same risk to developing fetuses that Zika does.”

West Nile in human placenta
West Nile virus (green) grows in human placenta, where the cells are marked red with blue nuclei. (Credit: Nitin Arora/Washington U. in St. Louis)

Zika virus garnered worldwide attention beginning in 2015, when reports of an outbreak surfaced in Brazil. Alarm heightened when researchers linked Zika infection in pregnant women with the risk of bearing babies born with microcephaly, or abnormally small heads.

Miner, who helped develop mouse models of Zika virus infection during pregnancy while working in the laboratory of Michael Diamond, stumbled across a few scattered reports in medical literature suggesting that West Nile virus also could be spread from mother to child before birth, causing birth defects. But nobody had rigorously tested the possibility by comparing multiple viruses in parallel.

Assessing West Nile’s damage

Miner and graduate student and first author Derek Platt, decided to find out whether West Nile and a related virus known as Powassan could cause similar brain damage and fetal death. Like Zika, both belong to the flavivirus family and target neural tissues.

West Nile infects thousands of people every year in the United States. Most never know they have it, but about 1,000 people a year develop life-threatening brain infections that can cause persistent neurological problems.

Powassan is a rare virus spread by ticks. There are only a few dozen documented cases of disease caused by the virus in the US over the past decade, mostly in the Great Lakes region.

As part of the study and for comparison, Platt and Miner also wanted to study the effects of two mosquito-borne viruses only distantly related to Zika: chikungunya and Mayaro. Both are found in Brazil and can cause arthritis.

They injected female mice at day six of their pregnancies with one of the four viruses, then examined the placentas and fetuses a week later.

All four viruses infected the placentas and fetuses, but levels of West Nile virus were 23- to 1,500-fold higher than those of the other three viruses in the placentas, and 3,000- to 16,000-fold higher in the heads of the fetal mice.

In addition, brain tissue from West Nile-infected fetuses showed severe damage under the microscope, while brain tissue from chikungunya-infected fetuses appeared healthy.

Drug keeps mouse memory sharp after West Nile

Miner and Platt also found that about half of the fetuses whose mothers were infected with West Nile or Powassan virus died within 12 days of infection, but no fetuses from mothers infected with chikungunya or Mayaro did.

A possible threat to people

Researchers then infected human placentas with one of the four viruses or Zika virus. They found that the three flaviviruses—Zika, West Nile, and Powassan—multiplied in human placentas while chikungunya and Mayaro did not.

“Millions of people were infected with Zika in a short time, and I think that made it easier to see, in people, that Zika virus could infect and cross the placenta and cause fetal damage,” says Miner, who is also an assistant professor of molecular microbiology and of pathology and immunology.

“But our data show that other flaviviruses have the same capacity, at least in mice. It may be that it’s just more difficult to prove a link between West Nile and birth defects because the number of cases is smaller and infections are more sporadic.”

Additional epidemiologic studies to determine whether West Nile infection can cause miscarriage and brain damage in people may be prompted by the study, Miner says.

“I don’t want people to think that we’re saying West Nile is definitely a threat to pregnant women and their babies. We’re saying it’s possible. But until we know for sure, it’s always a good idea to wear bug repellant.”

How West Nile virus can trigger memory loss

The National Institutes of Health; Mid-America Transplant Foundation; Washington University’s Children’s Discovery Institute; the Rheumatology Research Foundation; Burroughs Wellcome Fund Investigators in Pathogenesis of Infectious Disease Award; Washington University Chancellor’s Graduate Fellowship Program; and the NIH Initiative for Maximizing Student Development funded the work.

Source: Washington University in St. Louis