Titre

Identification of GBF1 as a cellular factor required for hepatitis E virus RNA replication.

Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Farhat, R.
Auteure/Auteur
Ankavay, M.
Auteure/Auteur
Lebsir, N.
Auteure/Auteur
Gouttenoire, J.
Auteure/Auteur
Jackson, C.L.
Auteure/Auteur
Wychowski, C.
Auteure/Auteur
Moradpour, D.
Auteure/Auteur
Dubuisson, J.
Auteure/Auteur
Rouillé, Y.
Auteure/Auteur
Cocquerel, L.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1462-5822
Statut éditorial
Publié
Date de publication
2018-01
Volume
20
Numéro
1
Première page
1
Dernière page/numéro d’article
11
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The hepatitis E virus (HEV) genome is a single-stranded, positive-sense RNA that encodes three proteins including the ORF1 replicase. Mechanisms of HEV replication in host cells are unclear, and only a few cellular factors involved in this step have been identified so far. Here, we used brefeldin A (BFA) that blocks the activity of the cellular Arf guanine nucleotide exchange factors GBF1, BIG1, and BIG2, which play a major role in reshuffling of cellular membranes. We showed that BFA inhibits HEV replication in a dose-dependent manner. The use of siRNA and Golgicide A identified GBF1 as a host factor critically involved in HEV replication. Experiments using cells expressing a mutation in the catalytic domain of GBF1 and overexpression of wild type GBF1 or a BFA-resistant GBF1 mutant rescuing HEV replication in BFA-treated cells, confirmed that GBF1 is the only BFA-sensitive factor required for HEV replication. We demonstrated that GBF1 is likely required for the activity of HEV replication complexes. However, GBF1 does not colocalise with the ORF1 protein, and its subcellular distribution is unmodified upon infection or overexpression of viral proteins, indicating that GBF1 is likely not recruited to replication sites. Together, our results suggest that HEV replication involves GBF1-regulated mechanisms.
PID Serval
serval:BIB_DFC0BBF3D33A
DOI
PMID
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Date de création
2017-11-15T08:21:50.909Z
Date de création dans IRIS
2025-05-21T05:12:56Z