Zika virus in pregnant monkeys stymies fetal growth

"Initially I thought this was a story about Zika, but as I looked at the results I think this is also a story about how fetal infections in general affect developmental trajectories,” says Eliza Bliss-Moreau. (Credit: Getty Images)

Zika virus infection in pregnant rhesus macaques slows fetal growth and affects how infants and mothers interact in the first month of life, according to a new study.

The findings have has implications for both humans exposed to Zika virus and for other viruses that can cross the placenta, including SARS-CoV2, responsible for the COVID-19 pandemic, researchers say.

“Initially I thought this was a story about Zika, but as I looked at the results I think this is also a story about how fetal infections in general affect developmental trajectories,” says Eliza Bliss-Moreau, professor of psychology at the University of California, Davis and senior author of the paper published in Science Translational Medicine.

In most people, Zika virus infection causes mild or no symptoms and leaves long-lasting immunity. But during pregnancy, the virus can cross the placenta and cause damage to the nervous system of the fetus. In extreme cases, it can cause microcephaly in humans.

While no local transmission of the virus has been reported in the US since 2018, the mosquitoes that carry Zika virus continue to expand their range throughout Africa, the Americas, Asia, and the Pacific.

Researchers previously showed that Zika virus could enter the fetal brain in pregnant macaques. The new study looked at the effects of Zika infection during the second trimester of pregnancy on infants up to a month after birth.

Mom-baby bonding

Pregnant animals did not become visibly ill with the virus, but ultrasounds showed fetal growth slowed after infection, says Florent Pittet, a project scientist. At birth, Zika-exposed infants were “at the low end” of the range for head size in rhesus macaques.

“They were smaller overall,” he says. Higher levels of circulating Zika virus corresponded with longer delays in growth.

After birth, the researchers tracked the development of sensory and motor skills—using tests similar to those used for human babies—and interaction with the mother.

“The trajectory was quite different,” Pittet says. Right after birth, infant monkeys spend a lot of time on their mother but start to separate after about two weeks. But the Zika infants spent much more time clinging to their mothers through the first month.

It’s not clear whether the mother or the infant is initiating this contact, Bliss-Moreau says. “We know that moms will keep hold of infants that are having challenges,” she says.

Virus during pregnancy

Surprisingly, growth delays and effects on mother-infant interactions were greater in male than in female infants, although both showed delays compared to uninfected controls. Infectious disease studies in animals tend to use one sex (usually male) to avoid confounding effects, but potentially missing such sex differences.

Additionally, the animals were housed in established social groups of multiple adult females (including their mother), a single male, and other male and female infants of about the same age. This allows the infants to learn from each other and from the adults, Pittet says.

“The presence of unrelated adults and infants in the social group is a critical factor for normative development,” he says. “Offering such a social rearing environment is tons of additional work but ensures a lot more relevance to developmental studies.”

Upcoming papers will describe the monkeys’ growth through the first two years of life. Zika virus exposure during pregnancy sets off a cascade of consequences that may not appear until later in development, Pittet says.

The finding that outcomes correlate with viral load during pregnancy offers opportunities to intervene, the researchers say. A drug or vaccine would not have to completely eliminate the virus to be beneficial. This may be generally true for other infections that can affect the fetus, such as COVID.

“Anything you can do to reduce viral load is a good thing for infant development,” Bliss-Moreau says.

A 2019 study by CNPRC scientists, in collaboration with the National Institute of Allergy and Infectious Diseases, found that an experimental Zika vaccine lowered levels of circulating viruses in pregnant macaques.

Additional coauthors are from UC Davis CNPRC. The National Institutes of Health supported the work.

Source: UC Davis