Big month for our group, as we have two papers out from Dr. Cynthia McMillen and PMI PhD candidate, Austin Hertel!
In Nature Communications, Dr. McMillen and first author, Dr. Christina Megli from Magee-Women’s Research Institute, demonstrate the susceptibility of the human placenta to Oropouche orthobunyavirus, which has been the cause of an outbreak in South and Central America – and for the first time – resulted in fatalities.
This recent outbreak has also revealed a previously unrecognized severe outcome in human infection: vertical transmission and adverse outcomes in newborns. Dr. McMillen has previously demonstrated the susceptibility of human placenta to a related bunyavirus, Rift Valley fever virus. The placenta is a complex, multi-structured organ composed of several cell types and regions. Using both trophoblast stem cell derived in vitro cultures and organoid models, alongside ex vivo placenta tissue, the team demonstrated the susceptibility of these cells and tissues to Oropouche virus (OROV).
Using a historic strain which we had at the start of the current outbreak, OROV-BeAn19991, the group first identified that OROV replicates to relatively high titers in human trophoblast cultures and organoids. Cytotrophoblasts and syncytiotrophoblasts are two distinct cell types within the placenta that help facilitate nutrient exchange between mother and fetus. OROV-BeAn19991 replicated to high titer in the cytotrophoblasts and resulted in the induction of interferon-lambda 1, while resulting in a lower titer in syncytiotrophoblasts. Similarly, in trophoblast organoids, which contain trophoblasts in layers that more similarly replicate the natural structure of the placenta, there was a marked increase in OROV infection.
The team was able to collect term placenta following live births and use this tissue to determine infectivity of OROV in an ex vivo model system. Placenta were obtained across several gestational ages (32 to 39 weeks) and separated into villous, chorionic membrane, amniotic membrane, fetal membrane and decidua. OROV was able to replicate within villous, chorionic membrane, amniotic membrane and fetal membrane across 72 hours. However, sustained replication was not seen in decidua culture. Further, samples obtained from 39 weeks gestation did not support OROV replication.
These data show that trophoblasts and placenta tissue are susceptible to the historic OROV-BeAn19991 strain. The development and characterization of models at the maternal-fetal interface are critical to the development of countermeasures for emergent viral infections.
The University of Pittsburgh School of Public Health did a great write-up on this publication, found here!
— Kaleigh Connors