Dépôt numérique

Spatio-temporal reorganization of the endolysosomal network by Zika virus

Uyar, Olus; Mérette, Oceanne; Torres, Viviana Andrea Barragan; Tremblay, Nicolas; Pichlmair, Andreas; Scaturro, Pietro et Chatel-Chaix, Laurent ORCID logoORCID: https://orcid.org/0000-0002-7390-8250 (2023). Spatio-temporal reorganization of the endolysosomal network by Zika virus In: 19th International Symposium on NeuroVirology, October 2–5, 2023, Montréal (Québec).

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Zika virus (ZIKV), a neurotropic flavivirus transmitted by mosquitoes, is associated with severe neurodevelopmental defects including neonate microcephaly. Increased cell death of neural progenitors in developping brain is believed to be one of the the primary cause of these neurological disorders. Major rearrangements of the cytoplasm is induced upon ZIKV infection, notably to form the viral replication factories within the endoplasmic reticulum (ER) network. Besides ER, the ZIKV induced-morphological remodeling of other cellular organelles, such as mitochondria and lysosomes, was shown to perturb cellular processes including apoptosis and immunity, allowing infected cells to release higher amounts of ZIKV progeny. With aim to better decipher the interplay between these remodeled organelles during ZIKV infection, we first performed immunofluorescence assays on ZIKV-infected liver cells which showed an accumulation of enlarged lysosomes in the perinuclear area enriched in viral replication factories, underlying a physical hijacking of lysosomes by ZIKV for the benefit of its replication. Concordantly, live cell confocal imaging of ZIKV-infected cells revealed a decrease in the motility of peripheral lysososmes which was accompagnied by an increase in the duration of lysosomemitochondria contacts. This correlated with a significant decrease in the number of mitochondria-lysosomal contact sites as shown by proximity ligation assays detecting TOMM20-LAMP1 and GDAP1-LAMP1 tethering complexes. Similar phenotypes were observed in cells infected with West Nile virus, another neurotropic flavivirus suggesting a conserved spatial hijacking mecanism. In parallel, using quantitative mass spectrometry, we identified multiple proteins differentially expressed in ZIKV-infected liver cells compared to control cells. Their subsequent gene ontology analysis identified hits involved in endolysosomal regulation and potentially orchestrating the lysosomal co-opting by ZIKV. Ongoing work with these lysosome-related proteins is underway to ultimately determine their contribution to ZIKV replication and cytopathic effects, whether beneficial or detrimental.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique P 100 Journal of NeuroVirology 23 (suppl. 1): S32-S33
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 04 janv. 2024 14:45
Dernière modification: 04 janv. 2024 14:45
URI: https://espace.inrs.ca/id/eprint/13950

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