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

Abstract

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.

Acute Rift Valley fever virus infection induces inflammatory cytokines and cell death in ex vivo rat brain slice culture

“…28025013) with random hexamer primers. Semi-quantitative real-time PCR was used as previously described [22] for the detection of cytokines and chemokines (IFN-α, IFN-β, IFN-γ, IL-1β, IL-18, IL-6, TNF-α, GRO/KC, MCP-1/CCL2) normalized within each slice to housekeeping gene β actin.…”

Arboviruses and pregnancy: are the threats visible or hidden?

“…Some arboviruses can replicate efficiently in maternal placental epithelial cells and in cyto- and syncytiotrophoblasts before infecting fetal tissues [ 99 ]. Placental damage following infection is due to infiltration of CD68+ and TCD8+ cells, expression of MMPs, cytokines (IFN-γ and TNF-α), and other immunological mediators (RANTES/CCL5 and VEGFR-2) which cause excessive inflammation and vascular dysfunction resulting in placental dysfunction and reduced maternal-fetal exchanges [ 100 , 101 ]. These changes are histologically manifested by lesions of chorioamnionitis, infarcts, ischemic necrosis with fibrin deposits, villitis and/or intervillitis, subchorionic thrombosis, calcifications, leukocytic infiltration, and Hofbauer cell hyperplasia.…”

Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice

“…Relative quantitation of type I IFNs cDNA was made from RNA isolated from RVFV-infected or uninfected liver homogenate of Lrp1 f/f and Lrp1 f/f Alb-Cre tissue at 3 dpi as previously described (40). Using TaqMan Multiplex Master Mix (Applied Biosystems), TaqMan Gene Expression Assay kits were used for IFNα and IFNβ (IFNα: Thermo Fisher Scientific, 4331182 and IFNβ: Thermo Fisher Scientific, 4331182), and data were normalized to GAPDH (Thermo Fisher Scientific, 4448489) and from uninfected liver tissue of both genotypes.…”