Metabolic reprogramming by Zika virus provokes inflammation in human placenta

Qian Chen (1) , Jordi Gouilly (1) , Yann J Ferrat (2) , Ana Espino (1) , Quentin Glaziou (1) , Géraldine Cartron (3) , Hicham El Costa (1) , Reem Al-Daccak (4) , Nabila Jabrane-Ferrat (1)

1 CPTP - Centre de Physiopathologie Toulouse Purpan
2 CERAG - Centre d'études et de recherches appliquées à la gestion
3 Department of Obstetrics and Gynecology [Toulouse]
4 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie

The recent outbreak of Zika virus (ZIKV) was associated with birth defects and pregnancy loss when maternal infection occurs in early pregnancy, but specific mechanisms driving placental insufficiency and subsequent ZIKV-mediated pathogenesis remain unclear. Here we show, using large scale metabolomics, that ZIKV infection reprograms placental lipidome by impairing the lipogenesis pathways. ZIKV-induced metabolic alterations provide building blocks for lipid droplet biogenesis and intracellular membrane rearrangements to support viral replication. Furthermore, lipidome reprogramming by ZIKV is paralleled by the mitochondrial dysfunction and inflammatory immune imbalance, which contribute to placental damage. In addition, we demonstrate the efficacy of a commercially available inhibitor in limiting ZIKV infection, provides a proof-of-concept for blocking congenital infection by targeting metabolic pathways. Collectively, our study provides mechanistic insights on how ZIKV targets essential hubs of the lipid metabolism that may lead to placental dysfunction and loss of barrier function.

Domaines: Endocrinologie et métabolisme; Virologie; Gynécologie et obstétrique; Immunité innée

Qian Chen, Jordi Gouilly, Yann J Ferrat, Ana Espino, Quentin Glaziou, et al.. Metabolic reprogramming by Zika virus provokes inflammation in human placenta. Nature Communications, 2020, 11 (1), pp.2967. ⟨10.1038/s41467-020-16754-z⟩. ⟨inserm-02878676⟩