Zika virus damages the human placental barrier and presents marked fetal neurotropism

Abstract

An unusually high incidence of microcephaly in newborns has recently been observed in Brazil. There is a temporal association between the increase in cases of microcephaly and the Zika virus (ZIKV) epidemic. Viral RNA has been detected in amniotic fluid samples, placental tissues and newborn and fetal brain tissues. However, much remains to be determined concerning the association between ZIKV infection and fetal malformations. In this study, we provide evidence of the transplacental transmission of ZIKV through the detection of viral proteins and viral RNA in placental tissue samples from expectant mothers infected at different stages of gestation. We observed chronic placentitis (TORCH type) with viral protein detection by immunohistochemistry in Hofbauer cells and some histiocytes in the intervillous spaces. We also demonstrated the neurotropism of the virus via the detection of viral proteins in glial cells and in some endothelial cells and the observation of scattered foci of microcalcifications in the brain tissues. Lesions were mainly located in the white matter. ZIKV RNA was also detected in these tissues by real-time-polymerase chain reaction. We believe that these findings will contribute to the body of knowledge of the mechanisms of ZIKV transmission, interactions between the virus and host cells and viral tropism.

Zika virus infection disrupts neurovascular development and results in postnatal microcephaly with brain damage

“…ZIKV has been detected in amniotic fluid, placental tissues, and fetal and newborn brains (Calvet et al, 2016;Driggers et al, 2016;Mlakar et al, 2016;Noronha et al, 2016), suggesting that ZIKV can cross the placenta and infect fetal brains. Furthermore, it has been reported that ZIKV can infect human placental macrophages and trophoblasts (Quicke et al, 2016).…”

Autopsy and Postmortem Studies Are Concordant: Pathology of Zika Virus Infection Is Neurotropic in Fetuses and Infants With Microcephaly Following Transplacental Transmission

“…The role of pathology should not be underestimated in coming to the conclusion that Zika virus causes fetal malformations. 22 The initial reports in February 2016 of the fetal pathology occurring in fetuses and neonates with intrauterine Zika virus infection and microcephaly and with destructive brain lesions and Zika virus infection, 9,10 together with pathology and autopsy findings in subsequent cases, [12][13][14] were important factors in determining the causal role of this virus in producing fetal malformations. A variety of ophthalmic changes have been identified in neonates with congenital microcephaly and Zika virus infection, 23 but none of the reported autopsies have included pathologic examination of the eyes to study these ocular abnormalities in detail.…”

Dengue infection in the nervous system: lessons learned for Zika and Chikungunya

“…In February 2016, the World Health Organization declared ZIKV infection a public health emergency, issuing a global alert about its relationship to cases of microcephaly, considering that the viral genome was found in blood samples and tissues of microcephalic neonates 27 . Moreover, amniotic fluid analysis of microcephalic fetuses from pregnant women found ZIKV infection, inferring transplacental transmission 5,28 . This fact could explain the increased number of microcephaly cases reported in Brazil.…”