Research ArticleEMERGING INFECTIONS

Zika virus–related neurotropic flaviviruses infect human placental explants and cause fetal demise in mice

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Science Translational Medicine  31 Jan 2018:
Vol. 10, Issue 426, eaao7090
DOI: 10.1126/scitranslmed.aao7090

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Fearsome flaviviruses

Although it was identified more than half a century ago, Zika virus’s impact on unborn children of infected pregnant women was only detected in the recent epidemic. Unfortunately, Zika virus may not be unique in its ability to afflict fetal damage. To investigate this possibility, Platt and colleagues infected pregnant immunocompetent mice with related viruses. Two other flaviruses, West Nile virus and Powassan virus, caused fetal demise. These viruses could also replicate in human maternal and fetal explant tissue. If these or other neurotropic flaviviruses take off in the human population, then we may again experience congenital infections with devastating effects.

Abstract

Although Zika virus (ZIKV) infection in pregnant women can cause placental damage, intrauterine growth restriction, microcephaly, and fetal demise, these disease manifestations only became apparent in the context of a large epidemic in the Americas. We hypothesized that ZIKV is not unique among arboviruses in its ability to cause congenital infection. To evaluate this, we tested the capacity of four emerging arboviruses [West Nile virus (WNV), Powassan virus (POWV), chikungunya virus (CHIKV), and Mayaro virus (MAYV)] from related (flavivirus) and unrelated (alphavirus) genera to infect the placenta and fetus in immunocompetent, wild-type mice. Although all four viruses caused placental infection, only infection with the neurotropic flaviviruses (WNV and POWV) resulted in fetal demise. WNV and POWV also replicated efficiently in second-trimester human maternal (decidua) and fetal (chorionic villi and fetal membrane) explants, whereas CHIKV and MAYV replicated less efficiently. In mice, RNA in situ hybridization and histopathological analysis revealed that WNV infected the placenta and fetal central nervous system, causing injury to the developing brain. In comparison, CHIKV and MAYV did not cause substantive placental or fetal damage despite evidence of vertical transmission. On the basis of the susceptibility of human maternal and fetal tissue explants and pathogenesis experiments in immunocompetent mice, other emerging neurotropic flaviviruses may share with ZIKV the capacity for transplacental transmission, as well as subsequent infection and injury to the developing fetus.

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