**Syncytiotrophoblast of Placentae from Women with Zika Virus Infection Has Altered Tight Junction Protein Expression and Increased Paracellular Permeability**

**Jael Miranda 1, Dolores Martín-Tapia 1, Yolotzin Valdespino-Vázquez 2, Lourdes Alarcón 1, Aurora Espejel-Nuñez 2, Mario Guzmán-Huerta 2, José Esteban Muñoz-Medina 3, Mineko Shibayama 4, Bibiana Chávez-Munguía 4, Guadalupe Estrada-Gutiérrez 2, Samuel Lievano 5, Juan Ernesto Ludert 4 and Lorenza González-Mariscal 1,\***


Received: 9 July 2019; Accepted: 26 September 2019; Published: 29 September 2019

**Abstract:** The cytotrophoblast of human placenta transitions into an outer multinucleated syncytiotrophoblast (STB) layer that covers chorionic villi which are in contact with maternal blood in the intervillous space. During pregnancy, the Zika virus (ZIKV) poses a serious prenatal threat. STB cells are resistant to ZIKV infections, ye<sup>t</sup> placental cells within the mesenchyme of chorionic villi are targets of ZIKV infection. We seek to determine whether ZIKV can open the paracellular pathway of STB cells. This route is regulated by tight junctions (TJs) which are present in the uppermost portion of the lateral membranes of STB cells. We analyzed the paracellular permeability and expression of E-cadherin, occludin, JAMs –B and –C, claudins -1, -3, -4, -5 and -7, and ZO-1, and ZO-2 in the STB of placentae from ZIKV-infected and non-infected women. In ZIKV-infected placentae, the pattern of expression of TJ proteins was preserved, but the amount of claudin-4 diminished. Placentae from ZIKV-infected women were permeable to ruthenium red, and had chorionic villi with a higher mean diameter and Hofbauer hyperplasia. Finally, ZIKV added to the basolateral surface of a trophoblast cell line reduced the transepithelial electrical resistance. These results sugges<sup>t</sup> that ZIKV can open the paracellular pathway of STB cells.

**Keywords:** zika virus; flavivirus; tight junctions; claudins; ZO-1; blood-placental barrier; placenta
