Type I interferon controls vertical transmission and fetoplacental infection of Oropouche virus

The current outbreak of the emerging arthropod-transmitted Oropouche virus (OROV) in South America has been epidemiologically linked to vertical transmissions, microcephaly, and stillbirths. Nevertheless, the impact of OROV infection during pregnancy has not been experimentally evaluated. To address how OROV infection might impact pregnancy outcome, we performed experiments in human cells and mice. Studies in cell cultures showed that the human trophoblast cell lines BeWo and JEG-3 are permissive to OROV infection (strain BeAn19991) and develop type I interferon (IFN)-dependent antiviral response. In our model, loss of type I IFN signaling in the dam resulted in the spread of virus to the placenta and fetus, whereas loss in the fetus alone was not sufficient to cause fetal infection. Collectively, our study shows that placental cells are susceptible to OROV infection and that the outcome for fetus depends on the integrity of the type I IFN immune response in the dam.