Uyar, Olus; Mérette, Oceanne; Torres, Viviana Andrea Barragan; Tremblay, Nicolas; Pichlmair, Andreas; Scaturro, Pietro et Chatel-Chaix, Laurent 
ORCID: 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).
Résumé
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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