USP15 Participates in Hepatitis C Virus Propagation through Regulation of Viral RNA Translation and Lipid Droplet Formation.
Animals
Cell Line
Cell Line, Tumor
Chlorocebus aethiops
Gene Expression Regulation
/ physiology
HEK293 Cells
Hepacivirus
/ genetics
Hepatitis C
/ metabolism
Hepatocytes
/ metabolism
Humans
Lipid Droplets
/ metabolism
Lipid Metabolism
/ physiology
Liver
/ metabolism
RNA Interference
/ physiology
RNA, Viral
/ genetics
Signal Transduction
/ genetics
Ubiquitin-Specific Proteases
/ genetics
Ubiquitination
/ genetics
Vero Cells
Virus Replication
/ genetics
HCV
deubiquitination
innate immunity
lipid
translation
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
30
09
2018
accepted:
23
12
2018
pubmed:
11
1
2019
medline:
20
11
2019
entrez:
11
1
2019
Statut:
epublish
Résumé
Hepatitis C virus (HCV) utilizes cellular factors for efficient propagation. Ubiquitin is covalently conjugated to the substrate to alter its stability or to modulate signal transduction. In this study, we examined the importance of ubiquitination for HCV propagation. We found that inhibition of deubiquitinating enzymes (DUBs) or overexpression of nonspecific DUBs impaired HCV replication, suggesting that ubiquitination regulates HCV replication. To identify specific DUBs involved in HCV propagation, we set up RNA interference (RNAi) screening against DUBs and successfully identified ubiquitin-specific protease 15 (USP15) as a novel host factor for HCV propagation. Our studies showed that USP15 is involved in translation of HCV RNA and production of infectious HCV particles. In addition, deficiency of USP15 in human hepatic cell lines (Huh7 and Hep3B/miR-122 cells) but not in a nonhepatic cell line (293T cells) impaired HCV propagation, suggesting that USP15 participates in HCV propagation through the regulation of hepatocyte-specific functions. Moreover, we showed that loss of USP15 had no effect on innate immune responses
Identifiants
pubmed: 30626683
pii: JVI.01708-18
doi: 10.1128/JVI.01708-18
pmc: PMC6401473
pii:
doi:
Substances chimiques
RNA, Viral
0
USP15 protein, human
EC 3.4.19.12
Ubiquitin-Specific Proteases
EC 3.4.19.12
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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