Clinical and epidemiologic evidence from the 2023-24 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 an unknown ability to infect the relevant tissues of the maternal-fetal interface; therefore, the mechanisms of vertical transmission are unknown. We use human cytotrophoblast and syncytiotrophoblast stem cell cultures, polarized trophoblast stem cell organoids, and placenta explants to demonstrate that OROV (BeAn19991) infects and replicates in... More
Clinical and epidemiologic evidence from the 2023-24 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 an unknown ability to infect the relevant tissues of the maternal-fetal interface; therefore, the mechanisms of vertical transmission are unknown. We use human cytotrophoblast and syncytiotrophoblast stem cell cultures, polarized trophoblast stem cell organoids, and placenta explants to demonstrate that OROV (BeAn19991) infects and replicates in human tissues of the maternal-fetal interface including cytotrophoblasts and the microbial-resistant cell, syncytiotrophoblast. Viral replication is robust within the first 24 hour post infection and infection may be dependent on gestational age. These data indicate tissues at the maternal-fetal interface are susceptible to OROV infection and may facilitate vertical transmission, leading to adverse pregnancy outcomes.
