Impact of Zika viral infection on first-trimester trophoblast cell function and its relevance in the regulation of the immune microenvironment

D VOTA; F MERECH; R RAMHORST; D PAPARINI; G CALO; C PÉREZ LEIRÓS; F GIOVANNONI; V HAUK ; C GARCIA

Mar del Plata

Congreso; LXIII Reunión Anual SAIC; 2018

The placenta may become exposed to micro-organisms throughout pregnancy such as viruses which pose a substantial threat to the embryo/fetus development. Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal growth restriction and fetal central nervous system malformations. Recently it has been reported that ZIKV infects first-trimester human trophoblast (Tb) cells enabling transplacental transmission. Since trophoblast cell function and metabolism are crucial to allow fetal growth and development, our aim is to determine the effect of ZIKV infection on first-trimester human Tb cells function and its implication in immune homeostasis maintenance. We infected the first-trimester human Tb-derived cell line Swan-71 with the local isolated ZIKV strain INEVH116141. High intracellular levels of viral RNA, with an extracellular viral production of 2.7 105 UFP/mL was detected. ZIKV induced an important antiviral response in Tb cells increasing the expression of IFN-beta/BST2/RIG/TRAF6 and viperin mRNAs. Also, an increased mRNA expression of pro-inflammatory cytokines (TNF-alpha/IL-6/IL-1beta) was found in Tb ZIKV infected cells. Alterations in the AHR/IDO1 pathway, crucial for the immune homeostasis maintenance and a dysregulation in the expression of specific glucose/amino acid carrier proteins GLUT1/3 and SNAT1/2, respectively were also determined. On the other hand, assays with synthetic analog of viral RNA, Poly I:C, induced a decrease of cellular migration after 24h of culture in wound healing assays (n=5; p