Biology subjects

Boyles, D. A.

Publications and source records attributed to Boyles, D. A..

3 recordsLinked to original sources

bioRxiv2024

Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal-fetal placental interface

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and {Delta}NSm infection, while live attenuated RVFV vaccines (LAVs; MP-12, {Delta}NSs, and {Delta}NSs/{Delta}NSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent in the maternal-facing side. Type-I and type-III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal-fetal interface. TeaserVaccine strains of Rift Valley fever virus have reduced infection and replication capacity in mammalian placenta

microbiology↗

bioRxiv2022

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, more recently, late-gestation miscarriages in African women. Here, we use a rat model of congenital RVF to identify cellular tropism, pathology, and local immune responses occurring in the placenta during vertical transmission. Infection of pregnant rats during late gestation (embryonic day 14) resulted in vertical transmission to the placenta and widespread viral infection throughout the decidua, basal zone, and labyrinth zone. Some pups delivered from infected dams appeared normal while others had gross signs of teratogenicity including fetal death. Histopathological lesions were detected in placenta from pups regardless of teratogenicity, while teratogenic pups had more widespread hemorrhage throughout multiple placenta layers. Teratogenic events were also associated with significant increases in pro-inflammatory cytokines, type I interferons, and chemokines within the placental tissue. Thus, we found that RVFV displays a high degree of tropism for all placental tissue layers, and that the degree of hemorrhage and inflammatory mediator production is highest in placenta from pups with adverse outcomes. This is the first detailed pathological study of the mechanisms of RVFV infection of placental tissue in a tractable rodent model of congenital RVF disease.

microbiology↗

bioRxiv2018

Rift Valley fever virus induces fetal demise through direct placental infection

Rift Valley fever virus (RVFV) infections in pregnant livestock are associated with high rates of fetal demise and have been linked to miscarriage in pregnant women. To address how acute RVFV infection during pregnancy causes detrimental effects on the fetus, we developed an immunocompetent pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their non-pregnant counterparts and that RVFV infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from infected asymptomatic pregnant rats. Virus distribution in infected dams was widespread, with a previously unrecognized preference for infection, replication, and tissue damage in the placenta. In human mid-gestation placental tissue, RVFV directly infected placental chorionic villi, with replication detected in the outermost syncytial layer. Our work identifies direct placental infection by RVFV as a mechanism for vertical transmission and points to the teratogenic potential of this virus in humans. This is the first time vertical transmission of RVFV has been shown in species other than livestock. This study highlights the potential impact of a future epidemic of this emerging mosquito-borne virus.

microbiology↗