Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis

Freppel, Wesley; Barragan Torres, Viviana Andrea; Uyar, Olus; Anton, Anaïs; Nouhi, Zaynab; Broquière, Mathilde; Mazeaud, Clément; Sow, Aïssatou Aïcha; Léveillé, Alexanne; Gilbert, Claudia; Tremblay, Nicolas; Owen, Jonathan E; Bemis, Chayenne L; Laulhe, Xavier; Lamarre, Alain ORCID: https://orcid.org/0000-0002-7913-871X; Neufeldt, Christopher John; Rodrigue-Gervais, Ian Gaël; Pichlmair, Andreas; Girard, Denis ORCID: https://orcid.org/0000-0002-3342-5027; Scaturro, Pietro; Hulea, Laura et Chatel-Chaix, Laurent ORCID: https://orcid.org/0000-0002-7390-8250 (2025). Dengue virus and Zika virus alter endoplasmic reticulum-mitochondria contact sites to regulate respiration and apoptosis iScience , vol. 28 , nº 111599. pp. 1-24. DOI: 10.1016/j.isci.2024.111599.

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Résumé

During infection, dengue virus (DENV) and Zika virus (ZIKV), two (ortho)flaviviruses of public health concern worldwide, induce alterations of mitochondria morphology to favor viral replication, suggesting a viral co-opting of mitochondria functions. Here, we performed an extensive transmission electron microscopy-based quantitative analysis to demonstrate that both DENV and ZIKV alter endoplasmic reticulum-mitochondria contact sites (ERMC). This correlated at the molecular level with an impairment of ERMC tethering protein complexes located at the surface of both organelles. Furthermore, virus infection modulated the mitochondrial oxygen consumption rate. Consistently, metabolomic and mitoproteomic analyses revealed a decrease in the abundance of several metabolites of the Krebs cycle and changes in the stoichiometry of the electron transport chain. Most importantly, ERMC destabilization by protein knockdown increased virus replication while dampening ZIKV-induced apoptosis. Overall, our results support the notion that flaviviruses hijack ERMCs to generate a cytoplasmic environment beneficial for sustained and efficient replication.

Type de document:	Article
Mots-clés libres:	Virology; Membranes; Cell biology; Proteomics; Metabolomics
Centre:	Centre INRS-Institut Armand Frappier
Date de dépôt:	06 janv. 2025 05:57
Dernière modification:	06 janv. 2025 05:57
URI:	https://espace.inrs.ca/id/eprint/16243

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