The Oropouche virus (OROV), historically associated with mild fevers and headaches, is now under international scrutiny following the current OROV outbreak (2023-2024). This outbreak revealed that the virus can lead to severe complications, including cases of mother-to-child transmission for the first time in history.
OROV was first isolated in 1955 in Trinidad and Tobago and has since caused over 80 outbreaks across the South and Central Americas. However, until the recent Brazilian outbreak, infections were self-limiting and typically presented only as symptomatic illnesses. This changed dramatically in Brazil, where researchers began documenting alarming cases of stillbirths, neonatal deaths, microcephaly, and other birth defects that seemed to be linked to OROV. Researchers in Brazil were able to demonstrate, for the first time, that they could detect OROV genetic material in the affected infants and found evidence of maternal antibodies, supporting the theory that OROV can cross the placenta during pregnancy, a phenomenon known as vertical transmission.
But how does a mosquito-borne virus penetrate one of the most complex protective barriers in the human body, the placenta? A research group at the University of Pittsburgh sought to answer this question using sophisticated laboratory models, including human placental cell cultures, 3D organoids, and human placental tissue samples. Their goal was to determine which placenta cells are susceptible to infection and how the virus spreads.
Their findings determined that the two main types of placental cells, cytotrophoblasts (CTBs) and syncytiotrophoblasts (STBs), supported high-level and active replication of OROV. They exhibited a significant increase in virus levels after just 12 hours of exposure, and this increase continued to rise over the next 48 hours. Similarly, their 3D trophoblast organoids, which simulate the tiny finger-like villi immersed in maternal blood, also became infected and showed viral particles on their surfaces.
Interestingly, while the CTBs became infected, they activated a robust antiviral response, producing high levels of interferon lambda (IFN-λ1), a crucial immune molecule. In contrast, STB and organoids produced little to no response level of IFN-λ. Although CTBs produced some IFN-λ, the levels varied across multiple exposures; however, STBs failed to mount a notable response. Â
In addition to cultured cells, the researchers examined placental tissues from different stages of pregnancy. They determined that OROV replicated more easily in the villous tissue and fetal membranes collected from mid-gestation pregnancy (32-36 weeks) compared to near-term pregnancies (38-40 weeks). This finding implies that the placenta could change susceptibility to viral replication during the various phases of pregnancy, and perhaps this mechanism potentially explains why some infections lead to fetal loss or birth defects, while others do not.
Even more interestingly, despite significant OROV replication, the infected tissue did not show any substantial inflammation or cytokine storms. There is potential that OROV can replicate “silently” without triggering an immune response sufficient to alert the mother’s immune system. This behavior is reminiscent of Rift Valley fever virus (RVFV), a bunyavirus that can cause miscarriage and stillbirth in infected mothers.
Researchers believe that a newly evolved OROV strain, with a combination of genetic segments from multiple regional origins, may partly explain the recent increase in incidence and severity of cases. Furthermore, the expansion of surveillance has enabled the detection of infections that may have gone unnoticed in earlier outbreaks.
These results highlight the importance of advanced lab models such as 3-D placental organoids and tissue explants in helping scientists understand how emerging viruses can endanger pregnancy. While these models cannot fully replicate the intricate immune dynamics of a living pregnancy, they will offer critical insight into which of these cells are targeted and how they may invade or transgress the placental barrier.
Nonetheless, the researchers emphasize that further studies, including in vivo animal models, are essential to identify the full pathway by which OROV is transmitted from mother to child and to explore any approaches that could improve recognition, detection, or prevention of congenital infection. With climate change and urbanization, OROV is spreading into new areas, and such research is crucial for protecting maternal and infant health.
For detailed insights into the symptoms, transmission, diagnosis, and prevention of Oropouche virus, visit our Oropouche Virus information page.
References: Megli CJ, Zack RK, McGaughey JJ, et al. Oropouche virus infects human trophoblasts and placenta explants. Nat Commun. 2025;16:6040. doi:10.1038/s41467-025-61138-w
