Rift Valley fever virus induces fetal demise through direct placental infection

Abstract

14Rift Valley fever virus (RVFV) infections in pregnant livestock are associated with high 15 rates of fetal demise and have been linked to miscarriage in pregnant women. To address how 16 acute RVFV infection during pregnancy causes detrimental effects on the fetus, we developed an 17 immunocompetent pregnant rodent model of RVFV infection. We found that pregnant rats were 18 more susceptible to RVFV-induced death than their non-pregnant counterparts and that RVFV 19 infection resulted in intrauterine fetal death and severe congenital abnormalities, even in pups from 20 infected asymptomatic pregnant rats. Virus distribution in infected dams was widespread, with a 21 previously unrecognized preference for infection, replication, and tissue damage in the placenta. 22In human mid-gestation placental tissue, RVFV directly infected placental chorionic villi, with 23 replication detected in the outermost syncytial layer. Our work identifies direct placental infection 24 by RVFV as a mechanism for vertical transmission and points to the teratogenic potential of this 25 virus in humans. This is the first time vertical transmission of RVFV has been shown in species 26

Rift Valley Fever: a Threat to Pregnant Women Hiding in Plain Sight?

“…Pathogens that are known to cause human fetal infection (Listeria, Toxoplasma, cytomegalovirus, Zika) infect extravillous trophoblasts and/or cytotrophoblasts but not syncytiotrophoblasts, which maintain high resistance to pathogens (53)(54)(55). RVFV, in contrast to these other fetal infections, appears capable of infecting both the syncytiotrophoblast and cytotrophoblast layers of the human placenta (50,51), which may portend the potential for in utero infection of human fetuses.…”

“…A small study from 1956 infected pregnant rodents with a mouse-passaged strain of RVFV, and virus was detected in murine embryos taken from sick dams, however no abortions or fetal death were reported (56). More recently, a rodent model of vertical infection was described in outbred Sprague-Dawley rats (50). Unlike mice, rats demonstrate a wider range of disease outcomes after infection with RVFV by different routes (57,58).…”

“…In Sprague-Dawley rats, RVFV was highly tropic for placental tissue in rats infected during late gestation (day 14 of a 21 day gestation period). At lower infectious doses of RVFV, pregnant dams remained healthy and disease-free yet delivered pups that were dead and full of virus (50). Some dams delivered a combination of live and dead pups, while others delivered only deceased offspring.…”