Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment.
Carcinoma, Hepatocellular
/ metabolism
Endoplasmic Reticulum
/ metabolism
Hepacivirus
/ physiology
Hepatitis C
/ genetics
Humans
Intracellular Membranes
/ metabolism
Lipid Droplets
/ physiology
Liver Neoplasms
/ metabolism
RNA, Viral
/ analysis
Spatio-Temporal Analysis
Tumor Cells, Cultured
Viral Nonstructural Proteins
/ metabolism
Virus Assembly
Virus Replication
CLEM
HCV
assembly
correlative light and electron microscopy
double-membrane vesicles
lipid droplet
lipid metabolism
plus-strand RNA virus
replication organelle
virus–host interaction
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
18 06 2019
18 06 2019
Historique:
received:
03
01
2019
revised:
05
04
2019
accepted:
17
05
2019
entrez:
20
6
2019
pubmed:
20
6
2019
medline:
5
8
2020
Statut:
ppublish
Résumé
The hepatitis C virus (HCV) is a major cause of chronic liver disease, affecting around 71 million people worldwide. Viral RNA replication occurs in a membranous compartment composed of double-membrane vesicles (DMVs), whereas virus particles are thought to form by budding into the endoplasmic reticulum (ER). It is unknown how these steps are orchestrated in space and time. Here, we established an imaging system to visualize HCV structural and replicase proteins in live cells and with high resolution. We determined the conditions for the recruitment of viral proteins to putative assembly sites and studied the dynamics of this event and the underlying ultrastructure. Most notable was the selective recruitment of ER membranes around lipid droplets where structural proteins and the viral replicase colocalize. Moreover, ER membranes wrapping lipid droplets were decorated with double membrane vesicles, providing a topological map of how HCV might coordinate the steps of viral replication and virion assembly.
Identifiants
pubmed: 31216478
pii: S2211-1247(19)30692-8
doi: 10.1016/j.celrep.2019.05.063
pii:
doi:
Substances chimiques
RNA, Viral
0
Viral Nonstructural Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3602-3617.e5Informations de copyright
Copyright © 2019 Department of Infectious Diseases, Molecular Virology, Heidelberg University. Published by Elsevier Inc. All rights reserved.