Congenital Rift Valley fever in Sprague Dawley rats is associated with diffuse infection and pathology of the placenta.

Rift Valley fever (RVF) is a disease of animals and humans associated with abortions in ruminants and late-gestation miscarriages in women. Here, we use a rat model of congenital RVF to identify tropisms, pathologies, and immune responses in the placenta during vertical transmission. Infection of late-gestation pregnant rats resulted in vertical transmission to the placenta and widespread infection throughout the decidua, basal zone, and labyrinth zone. Some pups from infected dams appeared normal while others had gross signs of teratogenicity including death. Histopathological lesions were detected in placenta from pups regardless of teratogenicity, while teratogenic pups had widespread hemorrhage throughout multiple placenta layers. Teratogenic events were associated with significant increases in placental pro-inflammatory cytokines, type I interferons, and chemokines. RVFV displays a high degree of tropism for all placental tissue layers and the degree of hemorrhage and inflammatory mediator production is highest in placenta from pups with adverse outcomes. Given the potential for RVFV to emerge in new locations and the recent evidence of emerging viruses, like Zika and SARS-CoV-2, to undergo vertical transmission, this study provides essential understanding regarding the mechanisms by which RVFV crosses the placenta barrier. Author summary: Rift Valley fever virus (RVFV) infections cause human health and economical burdens given its ability to induce high rates of abortions in ruminants and possible contributions towards late-term miscarriages in women. In this study, we have identified important structures in the placenta targeted by this emerging bunyavirus. Inflammation was associated with more severe fetal outcomes such as death and fetal deformities. The striking similarities between the pathologies of the placenta in this rodent model of congenital RVF and those observed in naturally infected ruminants highlight the utility of this rodent model. These findings may be further translated towards understanding the mechanisms involved in vertical transmission of RVFV in humans. [ABSTRACT FROM AUTHOR]