Zika virus infection of trophoblast cells modulates neural progenitor cell survival and metabolism

M CHEMEN; S RODRIGUEZ VARELA; D RIOS; A MARQUEZ; D PAPARINI; F MERECH; V HAUK; C PÉREZ LEIRÓS; L ROMORINI; C GARCIA; D VOTA

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Aim: Zika virus (ZIKV) infection during the first stages of pregnancy was pointed out as a risk factor related to a higher incidence of congenital neurological disorders. We have previously demonstrated that ZIKV infection of first trimester cytotrophoblast‐derived cells (Tb) impaired cell migration and reduced brain‐derived neurotrophic factor (BDNF). Interestingly, the vasoactive intestinal peptide (VIP) produced by the placenta decreased Tb susceptibility to ZIKV infection, restoring cell migration and metabolism. We aim to investigate the impact of Tb cell infection with ZIKV on human neural stem cell survival and the possible extended antiviral role of VIP during ZIKV infection of neural progenitors. Methodology: First trimester Tb-derived cell line Swan-71 (Tb) was infected with or without a local ZIKV isolate for 8h to obtain Tb-conditioned media (CMTbZ/CMTb). Neural stem cells (NSCs) derived from human embryonic stem cells were cultured with CMTb or CMTbZ or infected with ZIKV in the presence/absence of 10-50 nM VIP. Apoptosis, fatty acid and lipid droplet accumulation was measured by flow cytometry using a specific fluorescent Annexin V/IP kit or BODIPY FL C12 and BODIPY 493/503 fluorescent dyes, respectively. Infective viral particle production was measured by plaque assay. Results: CMTb protected NSCs from apoptosis (P