PREreviews of “Flaviviruses alter endoplasmic reticulum-mitochondria contacts to regulate respiration and apoptosis”

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Flaviviruses alter endoplasmic reticulum-mitochondria contacts to regulate respiration and apoptosis

by Wesley Freppel, Anaïs Anton, Zaynab Nouhi, Clément Mazeaud, Claudia Gilbert, Nicolas Tremblay, Viviana Andrea Barragan Torres, Aïssatou Aïcha Sow, Xavier Laulhé, Alain Lamarre, Ian Gaël Rodrigue-Gervais, Andreas Pichlmair, Pietro Scaturro, Laura Hulea, and Laurent Chatel-Chaix

Posted: March 10, 2023
Server: bioRxiv
DOI: 10.1101/2023.03.09.531853

Abstract

With no therapeutics available, there is an urgent need to better understand the pathogenesis of flaviviruses which constitute a threat to public health worldwide. During infection, dengue virus (DENV) and Zika virus (ZIKV), two flaviviruses 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 contacts (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, as well as NS4B expression 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.

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PREreview by Craig McCormick

Authored by Craig McCormick

We, the students of MICI5029/5049, a Graduate Level Molecular Pathogenesis Journal Club at Dalhousie University in Halifax, NS, Canada, hereby submit a review of the following BioRxiv preprint:
Flaviviruses alter endoplasmic reticulum-mitochondria contacts to regulate respiration and apoptosis
Wes…

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PREreviews of Flaviviruses alter endoplasmic reticulum-mitochondria contacts to regulate respiration and apoptosis

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