Report published in Nature Communications
A University of Pittsburgh team led by Cynthia McMillen, PhD, has demonstrated that insect-spread Oropouche virus (OROV) can evade antiviral defenses in the placenta and infect the vital organ that connects mother and baby during fetal development.
Generally known to spread a flu-like tropical illness, OROV has been endemic in parts of South and Central America since the 1950s. During a major outbreak in 2023–2024, however, doctors began seeing more cases and severe disease, including miscarriage, stillbirth and birth defects. Infection prior to birth raised concerns that OROV could be passed from mother to fetus—a process called vertical transmission.
In this new study, McMillen, research assistant professor of infectious diseases and microbiology, School of Public Health, and colleagues exposed lab-cultured human placenta tissue and cells to OROV. They determined that the virus could infect and replicate in the placenta, particularly in cytotrophoblasts and the syncytiotrophoblast, cells that form the organ’s outermost layer. This is the first study to provide direct evidence that OROV can infect human placental tissue.
OROV, like Rift Valley fever virus (RVFV), which is found in Africa and the Middle East, is a bunyavirus that can affect people and animals, causing fever, hemorrhagic fever, brain inflammation, kidney failure and blindness. RVFV has also been shown to infect the syncytiotrophoblast layer, suggesting direct infection of the placenta may lead to severe disease in newborns or miscarriage.
The syncytiotrophoblast layer normally resists viral infections, like Zika virus, a member of the flavivirus family. However, these studies suggest bunyaviruses may overcome the synctiotrophoblast’s antiviral properties. These findings help explain the possible mechanisms of transmission and associated birth defects observed during the 2023-24 outbreak.
OROV and RVFV use a shared cell-entry protein, Lrp1, which may explain their similar ability to infect placental cells. However, unlike OROV, RVFV has been linked to more obvious and severe liver damage in infected infants. Cache Valley virus is another bunyavirus found in North America known to infect humans and cause abortions in livestock. Recognizing the similarities and differences between bunyaviruses is a major goal of the McMillen group to identify which emerging infections might pose the greatest risks to pregnancy—and why.
These new study findings underscore the need for greater awareness, better diagnostic tools and more research into how emerging viruses like OROV might affect pregnancy. With climate change and increased travel making mosquito-borne viruses more widespread, understanding these risks is essential to protecting pregnant people and babies worldwide.
McMillen is senior author on the Nature Communications report. Christina Megli, MD, PhD, assistant professor of obstetrics, gynecology and reproductive sciences, School of Medicine, is first author. Additional authors are Rebecca Zack, School of Medicine; Jackson McGaughey and Ryan Hoehl, both Center for Vaccine Research; Taylor Snisky, Magee-Women’s Research Institute; and Amy Hartman, PhD, associate professor of infectious diseases and microbiology, School of Public Health.
The study was funded by the National Institutes of Health.
-Cynthia McMillen & Michele Dula Baum