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

McMillen, Cynthia M.; Arora, Nitin; Boyles, Devin A.; Albe, Joseph R.; Kujawa, Michael R.; Bonadio, Jeffrey; Coyne, Carolyn B.; Hartman, Amy L.

doi:10.1126/sciadv.aau9812

Cited by 50 publications

(75 citation statements)

References 33 publications

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“…In a recently published study by McMillen and co-workers, RVFV infection of human placental explants was shown for the first time, using a strain that was originally isolated from humans [11]. Our experiments with human placental explants corroborate this research and highlight the potential risks of RVFV infection during human pregnancy.…”

Section: Discussionsupporting

confidence: 82%

“…A cross-sectional study of Sudanese women correlated RVFV infection with an elevated miscarriage rate [10]. Notably, experiments with second-trimester human foetal tissue explants recently revealed that human syncytiotrophoblasts are susceptible and permissive to RVFV replication [11]. These reports warrant further studies to determine if RVFV infections pose a perhaps underestimated risk for human pregnancy.…”

Section: Introductionmentioning

confidence: 98%

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Rift Valley fever virus targets the maternal-foetal interface in ovine and human placentas

et al. 2020

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Background Rift Valley fever virus (RVFV) is an arbovirus of the order Bunyavirales that causes severe disease in ruminants and humans. Outbreaks in sheep herds are characterised by newborn fatalities and abortion storms. The association of RVFV infections with abortions of ovines and other ruminants is well recognized, whereas the pathology resulting in abortion has remained undescribed. Accumulating evidence suggests that RVFV is abortogenic in humans as well, warranting more research on the interaction of RVFV with the ruminant and human placenta. Methodology/Principal findings Pregnant ewes were inoculated with a highly virulent strain of RVFV and necropsied at different days post infection. Tissues were collected and analysed by PCR, virus isolation, and immunohistochemistry. The results show that RVFV replicates efficiently in maternal placental epithelial cells before the virus infects foetal trophoblasts. Moreover, the virus was shown to bypass the maternal epithelial cell layer by directly targeting foetal trophoblasts in the haemophagous zone, a region of the ovine placenta where maternal blood is in direct contact with foetal cells. Abortion was associated with widespread necrosis of placental tissues accompanied with severe haemorrhages. Experiments with human placental explants revealed that the same virus strain replicates efficiently in both cyto-and syncytiotrophoblasts. Conclusions/Significance This study demonstrates that RVFV targets the foetal-maternal interface in both ovine and human placentas. The virus was shown to cross the ovine placental barrier via two distinct routes, ultimately resulting in placental and foetal demise followed by abortion. Our finding that RVFV replicates efficiently in human trophoblasts underscores the risk of RVFV infection for human pregnancy.

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 98%

Rift Valley fever virus targets the maternal-foetal interface in ovine and human placentas

et al. 2020

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“…No virus was recovered from any sample with a viral RNA copy number of less than 8 logs. This was not surprising, given the sensitivity of the quantitative reverse transcription-PCR (qRT-PCR) assay, and similar findings have been reported by other investigators (36).…”

Section: Resultssupporting

confidence: 86%

Rift Valley Fever Virus Infection Causes Acute Encephalitis in the Ferret

Barbeau

Albe

Nambulli

et al. 2020

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Rift Valley fever virus (RVFV) is a pathogen of both humans and livestock in Africa and the Middle East. Severe human disease is associated with hepatitis and/or encephalitis. Current pathogenesis studies rely on rodents and nonhuman primates, which have advantages and disadvantages. We evaluated disease progression in Mustela putorius furo (the ferret) following intradermal (i.d.) or intranasal (i.n.) infection. Infected ferrets developed hyperpyrexia, weight loss, lymphopenia, and hypoalbuminemia. Three of four ferrets inoculated intranasally with RVFV developed central nervous system (CNS) disease that manifested as seizure, ataxia, and/or hind limb weakness at 8 to 11 days postinfection (dpi). Animals with clinical CNS disease had transient viral RNAemia, high viral RNA loads in the brain, and histopathological evidence of encephalitis. The ferret model will facilitate our understanding of how RVFV accesses the CNS and has utility for the evaluation of vaccines and/or therapeutics in preventing RVFV CNS disease. IMPORTANCE Animal models of viral disease are very important for understanding how viruses make people sick and for testing out drugs and vaccines to see if they can prevent disease. In this study, we identify the ferret as a model of encephalitis caused by Rift Valley fever virus (RVFV). This novel model will allow researchers to evaluate ways to prevent RVFV encephalitis.

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“…Importantly, high viral load was detected in the pup brains [99]. Moreover, human placenta explants were also found permissive to RVFV replication [116], confirming the observations of human vertical transmission [99].…”

Section: Mechanisms Of Neuronal Development Modulation By Arbovirusessupporting

confidence: 75%

“…Further studies showed that other arboviruses can infect human placenta and could be associated with fetal demise in animal models: a study showed that in human placental explants ZIKV, WNV, Mayaro virus (MAYV), and POWV, but not CHIKV, were able to replicate within different components of the tissue [115]. Similarly, RVFV can cross rat placenta and trigger deleterious effects on developing embryos [116]. Importantly, high viral load was detected in the pup brains [99].…”

Section: Mechanisms Of Neuronal Development Modulation By Arbovirusesmentioning

confidence: 99%

Neurocognitive impacts of arbovirus infections

Clé

Eldin

Briant

et al. 2020

J Neuroinflammation

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Arthropod-borne viruses or arbovirus, are most commonly associated with acute infections, resulting on various symptoms ranging from mild fever to more severe disorders such as hemorrhagic fever. Moreover, some arboviral infections can be associated with important neuroinflammation that can trigger neurological disorders including encephalitis, paralysis, ophthalmological impairments, or developmental defects, which in some cases, can lead to long-term defects of the central nervous system (CNS). This is well illustrated in Zika virus-associated congenital brain malformations but also in West Nile virus-induced synaptic dysfunctions that can last well beyond infection and lead to cognitive deficits. Here, we summarize clinical and mechanistic data reporting on cognitive disturbances triggered by arboviral infections, which may highlight growing public health issues spanning the five continents.

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

Abstract: Rift Valley fever virus infection of pregnant rats results in fetal infection and death, even in dams with no signs of illness.

Cited by 50 publications

References 33 publications

Rift Valley fever virus targets the maternal-foetal interface in ovine and human placentas

Rift Valley fever virus targets the maternal-foetal interface in ovine and human placentas

Rift Valley Fever Virus Infection Causes Acute Encephalitis in the Ferret

Neurocognitive impacts of arbovirus infections

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