Zika Virus Targets Multiple Tissues and Cell Types During the First Trimester of Pregnancy.

Abstract

The 2016 Zika virus (ZIKV) outbreak in the Americas has been characterized by an increased association frequency of fetal neuropathological abnormalities. To have a comprehensive and accurate knowledge of key elements of the clinically observed neurologic dysfunctions in Zika-infected babies, ZIKV transmission from mother to fetus needs to be deeply studied. Thus, it is important to determine the role of both virus-targeted cells and tissues within the mother-fetus interface. Cellular tropism and mechanisms of ZIKV transmission from mother to the fetus during early pregnancy still remain unknown on many aspects. To improve the characterization of the maternal-fetal ZIKV transmission, we have set up an ex vivo model using an organ culture approach with a light-invasive sampling from the first trimester of pregnancy samples. Thus, here we provide evidence that circulating epidemic ZIKV strains from Latin America widely target and destroy reproductive tissues, including the decidua basalis, fetal placenta, and umbilical cord. In addition, we show that ZIKV is able to differentially replicate in a large range of both maternal and fetal cells, including decidual fibroblasts and macrophages, fetal trophoblast and Hofbauer cells, as well as umbilical cord mesenchymal stem cells. This primary and broad ZIKV cellular tropism and the resulting abundant cytopathic-induced tissue effects during the first trimester of pregnancy show the upstream path of clinically observed congenital damages.