Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein

Flaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), subsequently stimulating appropriate cellular...

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Main Authors: Grégorie Lebeau, Jonathan Turpin, Etienne Frumence, Daed El Safadi, Wissal Harrabi, Philippe Desprès, Pascale Krejbich-Trotot, Wildriss Viranaïcken
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/14/6/1131
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author Grégorie Lebeau
Jonathan Turpin
Etienne Frumence
Daed El Safadi
Wissal Harrabi
Philippe Desprès
Pascale Krejbich-Trotot
Wildriss Viranaïcken
author_facet Grégorie Lebeau
Jonathan Turpin
Etienne Frumence
Daed El Safadi
Wissal Harrabi
Philippe Desprès
Pascale Krejbich-Trotot
Wildriss Viranaïcken
author_sort Grégorie Lebeau
collection DOAJ
description Flaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), subsequently stimulating appropriate cellular responses such as adaptation, autophagy or apoptosis. The correct redox conditions of this compartment are essential to forming native disulfide bonds in proteins. Zika virus (ZIKV) has the ability to induce persistent ER stress leading to the activation of UPR pathways. In this study, we wondered whether ZIKV affects the redox balance and consequently the oxidative protein folding in the ER. We found that ZIKV replication influences the redox state, leading to the aggregation of the viral envelope protein as amyloid-like structures in the infected cells.
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spelling doaj.art-41e267bf2a5e41dbb042b29d2560f24d2023-11-23T19:24:03ZengMDPI AGViruses1999-49152022-05-01146113110.3390/v14061131Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope ProteinGrégorie Lebeau0Jonathan Turpin1Etienne Frumence2Daed El Safadi3Wissal Harrabi4Philippe Desprès5Pascale Krejbich-Trotot6Wildriss Viranaïcken7PIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FrancePIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FrancePIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FrancePIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FrancePIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FrancePIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FrancePIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FrancePIMIT, Processus Infectieux en Milieu Insulaire Tropical, Université de La Réunion, INSERM UMR 1187, CNRS 9192, IRD 249, Plateforme CYROI, 97490 Sainte-Clotilde, Ile de La Réunion, FranceFlaviviruses replicate in membrane factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus viral protein accumulation contribute to ER stress. As a consequence, the host cell exhibits an Unfolded Protein Response (UPR), subsequently stimulating appropriate cellular responses such as adaptation, autophagy or apoptosis. The correct redox conditions of this compartment are essential to forming native disulfide bonds in proteins. Zika virus (ZIKV) has the ability to induce persistent ER stress leading to the activation of UPR pathways. In this study, we wondered whether ZIKV affects the redox balance and consequently the oxidative protein folding in the ER. We found that ZIKV replication influences the redox state, leading to the aggregation of the viral envelope protein as amyloid-like structures in the infected cells.https://www.mdpi.com/1999-4915/14/6/1131Zika virusunfolded protein responseER stressoligomerdisulfide bondamyloid aggregates
spellingShingle Grégorie Lebeau
Jonathan Turpin
Etienne Frumence
Daed El Safadi
Wissal Harrabi
Philippe Desprès
Pascale Krejbich-Trotot
Wildriss Viranaïcken
Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein
Viruses
Zika virus
unfolded protein response
ER stress
oligomer
disulfide bond
amyloid aggregates
title Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein
title_full Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein
title_fullStr Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein
title_full_unstemmed Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein
title_short Evidence of RedOX Imbalance during Zika Virus Infection Promoting the Formation of Disulfide-Bond-Dependent Oligomers of the Envelope Protein
title_sort evidence of redox imbalance during zika virus infection promoting the formation of disulfide bond dependent oligomers of the envelope protein
topic Zika virus
unfolded protein response
ER stress
oligomer
disulfide bond
amyloid aggregates
url https://www.mdpi.com/1999-4915/14/6/1131
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