Oropouche virus infects human placenta explants and trophoblast organoids

Clinical and epidemiologic evidence from the recent outbreak of Oropouche virus (OROV) has demonstrated increased severity in clinical disease and adverse pregnancy outcomes including miscarriage, stillbirth, and neonatal demise. Serological evidence suggests vertical transmission of OROV may be responsible. OROV has not been studied in the context of pregnancy and has unknown ability to infect the relevant tissues of the maternal-fetal interface, which have anti-viral properties; therefore, the mechanisms of vertical transmission are unknown. We used polarized human trophoblast stem cell organoids and human placenta explants to demonstrate that OROV (BeAn19991) infects and replicates in human tissues of the maternal-fetal interface including chorionic villi and the microbial-resistant cell, syncytiotrophoblast. Viral replication is robust within the first 24 hours post infection, and tissues from earlier gestations may be more susceptible to infection. These data indicate tissues at the maternal-fetal interface are susceptible to OROV infection and may facilitate vertical transmission, leading to adverse pregnancy outcomes.