Advertisement

 

 

Zika virus infects early- and mid-gestation human maternal-decidual tissues, inducing distinct innate tissue responses in the maternal-fetal interface.

Zika virus infects early- and mid-gestation human maternal-decidual tissues, inducing distinct innate tissue responses in the maternal-fetal interface.
Author Information (click to view)

Weisblum Y, Oiknine-Djian E, Vorontsov OM, Haimov-Kochman R, Zakay-Rones Z, Meir K, Shveiky D, Elgavish S, Nevo Y, Roseman M, Bronstein M, Stockheim D, From I, Eisenberg I, Lewkowicz AA, Yagel S, Panet A, Wolf DG,


Weisblum Y, Oiknine-Djian E, Vorontsov OM, Haimov-Kochman R, Zakay-Rones Z, Meir K, Shveiky D, Elgavish S, Nevo Y, Roseman M, Bronstein M, Stockheim D, From I, Eisenberg I, Lewkowicz AA, Yagel S, Panet A, Wolf DG, (click to view)

Weisblum Y, Oiknine-Djian E, Vorontsov OM, Haimov-Kochman R, Zakay-Rones Z, Meir K, Shveiky D, Elgavish S, Nevo Y, Roseman M, Bronstein M, Stockheim D, From I, Eisenberg I, Lewkowicz AA, Yagel S, Panet A, Wolf DG,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

Journal of virology 2016 12 14() pii

Abstract

Zika virus (ZIKV) has emerged as a cause of congenital brain anomalies and a range of placental-related abnormalities, highlighting the need to unveil the modes of maternal-to-fetal transmission. The most likely route of vertical ZIKV transmission is via the placenta. The earliest events of ZIKV transmission in the maternal decidua, representing the maternal-uterine aspect of the chimeric placenta, have remained unexplored. Here we show that ZIKV replicates in first-trimester human maternal-decidual tissues grown ex-vivo as 3D organ cultures. An efficient viral spread in the decidual tissues was demonstrated by the rapid upsurge and continued increase of tissue-associated ZIKV load and titers of infectious cell-free virus progeny, released from the infected tissues. Notably, maternal-decidual tissues obtained at mid-gestation remained similarly susceptible to ZIKV, whereas fetal-derived chorionic-villi demonstrated reduced ZIKV replication with increasing gestational age. A genome-wide transcriptome analysis revealed that ZIKV substantially upregulated the decidual tissue innate immune responses. Further comparison of the innate tissue-response patterns following parallel infections with ZIKV and human cytomegalovirus (HCMV), revealed that unlike HCMV, ZIKV did not induce immune-cell activation or trafficking responses in the maternal-fetal interface, but rather upregulated placental apoptosis and cell-death molecular functions. The data identify the maternal-uterine aspect of the human placenta as a likely site of ZIKV transmission to the fetus, and further reveal distinct patterns of innate tissue responses to ZIKV. Our unique experimental model and findings could further serve to study the initial stages of congenital ZIKV transmission and pathogenesis and evaluate the effect of new therapeutic interventions.

IMPORTANCE
In view of the rapid spread of the current ZIKV epidemic and the severe manifestations of congenital ZIKV infection, it is crucial to learn the fundamental mechanisms of viral transmission from the mother to the fetus. Our studies of ZIKV infection in the authentic tissues of the human maternal-fetal interface unveil a route of transmission whereby virus originating from the mother could reach the fetal compartment via efficient replication within the maternal decidual aspect of the placenta, cohabited by maternal and fetal cells. The identified distinct placental-tissue innate immune responses and damage pathways could provide a mechanistic basis for some of the placental developmental abnormalities associated with ZIKV infection. The findings in the unique model of the human decidua should pave the way to future studies examining the interaction of ZIKV with decidual immune cells, and to evaluation of therapeutic interventions aimed at the earliest stages of transmission.

Submit a Comment

Your email address will not be published. Required fields are marked *

sixteen + nineteen =

[ HIDE/SHOW ]