ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy

Abstract

The outbreak of the Zika Virus (ZIKV) and its association with fetal abnormalities have raised worldwide concern. However, the cellular tropism and the mechanisms of ZIKV transmission to the fetus during early pregnancy are still largely unknown. Therefore, we ex vivo modeled the ZIKV transmission at the maternal-fetal interface using organ culture from first trimester pregnancy samples. Here, we provide evidence that ZIKV strain circulating in Brazil infects and damages tissue architecture of the maternal decidua basalis, the fetal placenta and umbilical cord. We also show that ZIKV replicates differentially in a wide range of maternal and fetal cells, including decidual fibroblasts and macrophages, trophoblasts, Hofbauer cells as well as umbilical cord mesenchymal stem cells. The striking cellular tropism of ZIKV and its cytopathic-induced tissue injury during the first trimester of pregnancy could provide an explanation for the irreversible congenital damages.

Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities

“…Whether ZIKV infects epidermal stem cells or haematopoietic stem cells remains to be determined. To address how ZIKV may bypass the placenta barrier to vertically transmit from mothers to fetuses, studies using mid- and late-gestation placentas and explants from first-trimester chorionic villi found ZIKV infection of many cell types, including placental macrophages, called Hofbauer cells, trophoblasts, umbilical cord mesenchymal stem cells and endothelial cells (Bayer et al, 2016; El Costa et al, 2016; Quicke et al, 2016; Tabata et al, 2016). Together, these results suggest multiple routes of vertical transmission.…”

Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

“…This condition likely occurs during the first trimester of pregnancy 8 , although placental cells appear to be protected against ZIKV infection by a constitutive interferon (IFN)-λ 1 response 9 . Indeed, three recent studies showed that human primary placental macrophages, trophoblasts and fibroblasts of the maternal decidua basalis were permissive to ZIKV productive infection in vitro [10][11][12] . Additional studies demonstrated that ZIKV can cross the placental barrier either via uterine vessels or by an ascending route as recently demonstrated in a mouse model of vaginal ZIKV infection 13 .…”

Zika virus infection of first-trimester human placentas: utility of an explant model of replication to evaluate correlates of immune protection ex vivo

“…In this regard, invasion of basal decidua and uterine blood vessels by ZIKV-infected cytotrophoblasts could contribute to prolonged maternal viremia. ZIKV has been shown to replicate and produce infectious progeny in intact decidual explants and primary decidual macrophages [69–71*]. We showed that ZIKV replication in epithelial cells of endometrial glands in basal decidua is highly productive and could amplify the viral load in the maternal blood space where cell columns develop and increase the overall risk of transplacental transmission.…”

“…Drawing indicates sites of infection and cell types identified in studies of ZIKV replication in explants that model development in first-trimester human placentas and basal decidua and primary cells from the amniochorionic membranes [62**,71*]. Red virions and graduated arrows in basal and parietal decidua symbolize viremia (red) and viral dissemination from maternal blood stream, ZIKV-infected cells (red).…”