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

Détails

ID Serval
serval:BIB_DFC0BBF3D33A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Identification of GBF1 as a cellular factor required for hepatitis E virus RNA replication.
Périodique
Cellular microbiology
Auteur(s)
Farhat R., Ankavay M., Lebsir N., Gouttenoire J., Jackson C.L., Wychowski C., Moradpour D., Dubuisson J., Rouillé Y., Cocquerel L.
ISSN
1462-5822 (Electronic)
ISSN-L
1462-5814
Statut éditorial
Publié
Date de publication
01/2018
Peer-reviewed
Oui
Volume
20
Numéro
1
Pages
1-11
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.

Pubmed
Web of science
Création de la notice
15/11/2017 10:21
Dernière modification de la notice
20/08/2019 17:04
Données d'usage