Oropouche virus infects human neural progenitor cells and alters the growth of brain organoids.

Oropouche virus (OROV), is the etiologic agent of Oropouche fever (OROF), an emerging zoonotic disease that has been prevalent in South and Central America since the 1960s. Starting late 2023, the current outbreak has raised concern about vertical transmission and potential adverse pregnancy outcomes. While serological evidences and recent studies support the vertical transmission of OROV, how infection affects the fetal brain remains unclear. Here, we show that a strain of OROV, FG_2020, phylogenetically related to the epidemic strain, efficiently and productively infects human neural progenitor cells and iPSC-derived brain organoids. The main phenotypic effect is proliferation arrest associated with apoptosis leading to the loss of neural rosette organization, a key feature of neuroprogenitors in culture that mimics the polarized architecture of brain development. These data indicates that fetal brain is susceptible to OROV infection and that vertical transmission during the first months of pregnancy could lead to pathological effects on brain development.