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

## TL;DR

This study shows that the Oropouche virus can infect the placenta and fetus in mice, and the mother's type I interferon response is crucial for protecting the fetus.

## Contribution

The study experimentally demonstrates the role of maternal type I IFN signaling in preventing fetal OROV infection.

## Key findings

- OROV can cross the hematoplacental barrier and cause congenital infection in mice.
- Maternal IFNAR1 response limits viral spreading and fetal susceptibility to OROV infection.
- Fetal IFNAR1 deletion does not affect fetal susceptibility to OROV infection.

## Abstract

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.

•OROV can cross the hematoplacental barrier and cause congenital infection in mice•Maternal IFNAR1 response limits viral spreading and fetal susceptibility to OROV infection•Fetal IFNAR1 deletion does not affect fetal susceptibility to OROV infection•Maternal or fetal IFNLR1 deletion does not affect susceptibility to OROV infection

OROV can cross the hematoplacental barrier and cause congenital infection in mice

Maternal IFNAR1 response limits viral spreading and fetal susceptibility to OROV infection

Fetal IFNAR1 deletion does not affect fetal susceptibility to OROV infection

Maternal or fetal IFNLR1 deletion does not affect susceptibility to OROV infection

Immunology; Virology