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Sci Adv. 2018 Dec 5;4(12):eaau9812. doi: 10.1126/sciadv.aau9812. eCollection 2018 Dec.

Rift Valley fever virus induces fetal demise in Sprague-Dawley rats through direct placental infection.

Author information

1
Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA.
2
Department of Infectious Diseases and Microbiology, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA.
3
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, USA.
4
Department of Pathology, Magee Women's Hospital of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
5
Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
6
Center for Microbial Pathogenesis, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

Abstract

Rift Valley fever virus (RVFV) infections in pregnant livestock cause high rates of fetal demise; miscarriage in pregnant women has also been associated with RVFV infection. To address how RVFV infection during pregnancy causes detrimental effects on the fetus, we developed a pregnant rodent model of RVFV infection. We found that pregnant rats were more susceptible to RVFV-induced death than their nonpregnant 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. This is the first study to show vertical transmission of RVFV with a lethal outcome in a species other than livestock. This study highlights the potential impact of a future epidemic of this emerging mosquito-borne virus.

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