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

McMillen, Cynthia M.; Hartman, Amy L.

doi:10.1128/jvi.01394-19

Cited by 13 publications

(17 citation statements)

References 70 publications

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“…Mosquitoes transmit RVFV to humans, but direct contact with infected animals, aborted foetal material, and consumption of raw milk also have been shown to correlate with transmission in endemic RVFV regions [14][15][16]. As in livestock, RVFV, transmitted to pregnant women, has been associated with miscarriage and foetal disease [17]. Studies of RVFV vertical transmission in humans and its effect on human pregnancy and the foetus have so far been scarce and mostly limited to case reports, such as an RVFV-infected pregnant woman delivering a newborn with a rash, an enlarged liver and spleen, and jaundice [18].…”

Section: Introductionmentioning

confidence: 99%

Rift Valley Fever Virus Propagates in Human Villous Trophoblast Cell Lines and Induces Cytokine mRNA Responses Known to Provoke Miscarriage

Gwon

Mahani

Nagaev

et al. 2021

Viruses

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The mosquito-borne Rift Valley fever (RVF) is a prioritised disease that has been listed by the World Health Organization for urgent research and development of counteraction. Rift Valley fever virus (RVFV) can cause a cytopathogenic effect in the infected cell and induce hyperimmune responses that contribute to pathogenesis. In livestock, the consequences of RVFV infection vary from mild symptoms to abortion. In humans, 1–3% of patients with RVFV infection develop severe disease, manifested as, for example, haemorrhagic fever, encephalitis or blindness. RVFV infection has also been associated with miscarriage in humans. During pregnancy, there should be a balance between pro-inflammatory and anti-inflammatory mediators to create a protective environment for the placenta and foetus. Many viruses are capable of penetrating that protective environment and infecting the foetal–maternal unit, possibly via the trophoblasts in the placenta, with potentially severe consequences. Whether it is the viral infection per se, the immune response, or both that contribute to the pathogenesis of miscarriage remains unknown. To investigate how RVFV could contribute to pathogenesis during pregnancy, we infected two human trophoblast cell lines, A3 and Jar, representing normal and transformed human villous trophoblasts, respectively. They were infected with two RVFV variants (wild-type RVFV and RVFV with a deleted NSs protein), and the infection kinetics and 15 different cytokines were analysed. The trophoblast cell lines were infected by both RVFV variants and infection caused upregulation of messenger RNA (mRNA) expression for interferon (IFN) types I–III and inflammatory cytokines, combined with cell line-specific mRNA expression of transforming growth factor (TGF)-β1 and interleukin (IL)-10. When comparing the two RVFV variants, we found that infection with RVFV lacking NSs function caused a hyper-IFN response and inflammatory response, while the wild-type RVFV suppressed the IFN I and inflammatory response. The induction of certain cytokines by RVFV infection could potentially lead to teratogenic effects that disrupt foetal and placental developmental pathways, leading to birth defects and other pregnancy complications, such as miscarriage.

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Section: Introductionmentioning

confidence: 99%

Rift Valley Fever Virus Propagates in Human Villous Trophoblast Cell Lines and Induces Cytokine mRNA Responses Known to Provoke Miscarriage

Gwon

Mahani

Nagaev

et al. 2021

Viruses

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“…For instance, RVFV, as an arbovirus, is strongly associated with fetal loss and/or stillbirth in pregnant domesticated animals, where some same outcomes have been observed in pregnant women infected by RVFV. [171][172][173] In humans, RVFV could infect placental cytotrophoblasts (CTBs) and STBs in ex vivo experiment, which could highlight the possibility of vertical transmission. 174 Indeed, the maternal-fetal transmission of RVFV in the third trimester was reported in a case study, while the specific transplacental route of RVFV is still unclear.…”

Section: Other Emerging Virusesmentioning

confidence: 99%

Viral Infections During Pregnancy: The Big Challenge Threatening Maternal and Fetal Health

Cao

2021

Maternal-Fetal Medicine

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Viral infections during pregnancy are associated with adverse pregnancy outcomes, including maternal and fetal mortality, pregnancy loss, premature labor, and congenital anomalies. Mammalian gestation encounters an immunological paradox wherein the placenta balances the tolerance of an allogeneic fetus with protection against pathogens. Viruses cannot easily transmit from mother to fetus due to physical and immunological barriers at the maternal-fetal interface posing a restricted threat to the fetus and newborns. Despite this, the unknown strategies utilized by certain viruses could weaken the placental barrier to trigger severe maternal and fetal health issues especially through vertical transmission, which was not fully understood until now. In this review, we summarize diverse aspects of the major viral infections relevant to pregnancy, including the characteristics of pathogenesis, related maternal-fetal complications, and the underlying molecular and cellular mechanisms of vertical transmission. We highlight the fundamental signatures of complex placental defense mechanisms, which will prepare us to fight the next emerging and re-emerging infectious disease in the pregnancy population.

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“…Rainy seasons can wreak havoc on agricultural industries due to heightened transmission of RVFV to cows, sheep, and goats leading to high rates of fetal abortions (10-40%, 10-60%, and 25-90%, respectively) and neonatal death. Susceptibility to death after RVFV infection occurs in an age-dependent manner; neonates are significantly more susceptible than adult animals (McMillen and Hartman, 2021). Newborn and older lamb mortality can reach approximately 90% and 30%, respectively (Erasmus and Coetzer, 1981).…”

Section: Background/introductionmentioning

confidence: 99%

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

McMillen

Boyles

Kostadinov

et al. 2022

Preprint

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Rift Valley fever (RVF) is a disease of animals and humans associated with concomitant 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 placental tissue. Thus, we found that 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. 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.

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

Cited by 13 publications

References 70 publications

Rift Valley Fever Virus Propagates in Human Villous Trophoblast Cell Lines and Induces Cytokine mRNA Responses Known to Provoke Miscarriage

Rift Valley Fever Virus Propagates in Human Villous Trophoblast Cell Lines and Induces Cytokine mRNA Responses Known to Provoke Miscarriage

Viral Infections During Pregnancy: The Big Challenge Threatening Maternal and Fetal Health

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

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