Title :

Hepatitis C virus alters the morphology and function of peroxisomes

Author(s) :

Martin De Fourchambault, Esther [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Callens, Nathalie [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Saliou, Jean-Michel [Auteur]
Protéomique et Peptides Modifiés - PLBS [P3M]
Fourcot, Marie [Auteur]
Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41
Delos, Oceane [Auteur]
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Barois, Nicolas [Auteur]
Plateforme BioImaging Center Lille - PLBS [BICeL]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Thorel, Quentin [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Ramirez, Santseharay [Auteur]
Bukh, Jens [Auteur]
Cocquerel, Laurence [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Bertrand-Michel, Justine [Auteur]
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
MetaboHUB
Marot, Guillemette [Auteur]
MOdel for Data Analysis and Learning [MODAL]
METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
Sebti, Yasmine [Auteur]
Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011
Dubuisson, Jean [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
Rouille, Yves [Auteur]
Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Journal title :

Frontiers in Microbiology

Abbreviated title :

Front. Microbiol.

Volume number :

14

Pages :

1254728

Publisher :

Frontiers Media SA

Publication date :

2023-09-21

ISSN :

1664-302X

English keyword(s) :

hepatitis C virus
HCV genotype
peroxisome
proximity biotinylation
APEX2
CRISPR-Cas9
ROS

HAL domain(s) :

Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologie
Sciences du Vivant [q-bio]/Biologie cellulaire/Organisation et fonctions cellulaires [q-bio.SC]
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologie
Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses

English abstract : [en]

Despite the introduction of effective treatments for hepatitis C in clinics, issues remain regarding the liver disease induced by chronic hepatitis C virus (HCV) infection. HCV is known to disturb the metabolism of infected ...
Show more >Despite the introduction of effective treatments for hepatitis C in clinics, issues remain regarding the liver disease induced by chronic hepatitis C virus (HCV) infection. HCV is known to disturb the metabolism of infected cells, especially lipid metabolism and redox balance, but the mechanisms leading to HCV-induced pathogenesis are still poorly understood. In an APEX2-based proximity biotinylation screen, we identified ACBD5, a peroxisome membrane protein, as located in the vicinity of HCV replication complexes. Confocal microscopy confirmed the relocation of peroxisomes near HCV replication complexes and indicated that their morphology and number are altered in approximately 30% of infected Huh-7 cells. Peroxisomes are small versatile organelles involved among other functions in lipid metabolism and ROS regulation. To determine their importance in the HCV life cycle, we generated Huh-7 cells devoid of peroxisomes by inactivating the PEX5 and PEX3 genes using CRISPR/Cas9 and found that the absence of peroxisomes had no impact on replication kinetics or infectious titers of HCV strains JFH1 and DBN3a. The impact of HCV on peroxisomal functions was assessed using sub-genomic replicons. An increase of ROS was measured in peroxisomes of replicon-containing cells, correlated with a significant decrease of catalase activity with the DBN3a strain. In contrast, HCV replication had little to no impact on cytoplasmic and mitochondrial ROS, suggesting that the redox balance of peroxisomes is specifically impaired in cells replicating HCV. Our study provides evidence that peroxisome function and morphology are altered in HCV-infected cells.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017
• METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694
• Plateformes Lilloises en Biologie et Santé (PLBS) - UAR 2014 - US 41
• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Submission date :

2024-01-16T10:45:55Z
2024-01-16T11:12:56Z