D-071 | Zika virus infection of trophoblast cells hinders their ability to modulate the viability and metabolism of neural progenitor cells

Development
Author: Mathias Chemen | Email: mathias.chemen@yahoo.com.ar

Mathias Chemen^1°2°, Soledad Rodriguez-Varela^3°, Daiana Rios^1°,  Valentina Tacchino^1°2°, Fatima Merech^1°, Vanesa Hauk^1°, Claudia Pérez Leirós^1°,  Leonardo Romorini^3°, Cybele García^2°, Daiana Vota^1°

^1° Laboratorio de Inmunofarmacología. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
^2° Laboratorio de Estrategias Antivirales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
^3° LIAN-CONICET, Fundación FLENI

The placenta is an endocrine and metabolic fetal organ that contributes to fetal brain development. Zika virus (ZIKV) infection during early pregnancy is associated to adverse pregnancy outcomes including neurological disorders at or after birth. We aim to investigate the impact of first trimester trophoblast-derived (Tb) cells ZIKV infection on the viability and survival of human neural progenitor cells. First trimester Tb-derived cell line Swan-71 (Tb) was infected or not with a local ZIKV isolate for 8h to obtain Tb-conditioned media (CMTbZ/CMTb). Neural progenitor cells (NPs) derived from human embryonic stem cells were stimulated with CMTb or CMTbZ for 24h and metabolic and viability parameters were analyzed. Apoptosis, ROS production, long chain fatty acid (LCFA) and lipid droplet (LD) accumulation was measured by flow cytometry using a specific fluorescent Annexin V/IP kit or DCFH-DA, BODIPY FL C12 and BODIPY 493/503 fluorescent dyes, respectively. BDNF and CPT1 gene expression were measured by RT-qPCR. CMTb induced an increase in LCFA uptake and the gene expression of CPT1(P<0.05), the rate-limiting enzyme in the fatty acid β-oxidation. Moreover, CMTb protected NPs from apoptosis and decreased ROS production. Interestingly, this regulatory effect of Tb cells was not observed when NPs were cultured with CMTbZ. These results suggest that ZIKV infection of first trimester Tb cells hinders their ability to modulate the viability and metabolism of neural progenitor cells.