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 - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Saliou, Jean-Michel [Auteur]
Protéomique et Peptides Modifiés - PLBS [P3M]
Fourcot, Marie [Auteur]
Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 [PLBS]
Delos, Oceane [Auteur]
MetaboHUB-MetaToul
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Barois, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Plateforme BioImaging Center Lille - PLBS [BICeL]
Thorel, Quentin [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Ramirez, Santseharay [Auteur]
University of Copenhagen = Københavns Universitet [UCPH]
Bukh, Jens [Auteur]
University of Copenhagen = Københavns Universitet [UCPH]
Cocquerel, Laurence [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Bertrand-Michel, Justine [Auteur]
MetaToul Lipidomics
Institut des Maladies Métaboliques et Casdiovasculaires [UPS/Inserm U1297 - I2MC]
Marot, Guillemette [Auteur]
Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS]
MOdel for Data Analysis and Learning [MODAL]
Sebti, Yasmine [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Dubuisson, Jean [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Rouillé, Yves [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Journal title :

Frontiers in Microbiology

Pages :

1254728

Publisher :

Frontiers Media

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

Popular science :

Non

Collections :

• Laboratoire Paul Painlevé - UMR 8524

Source :

Harvested from HAL