Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment
Summary: 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 endoplas...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2019-06-01
|
Series: | Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719306928 |
id |
doaj-b47d6362fb914877b4724dfa3547b780 |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ji-Young Lee Mirko Cortese Uta Haselmann Keisuke Tabata Inés Romero-Brey Charlotta Funaya Nicole L. Schieber Yu Qiang Marie Bartenschlager Stephanie Kallis Christian Ritter Karl Rohr Yannick Schwab Alessia Ruggieri Ralf Bartenschlager |
spellingShingle |
Ji-Young Lee Mirko Cortese Uta Haselmann Keisuke Tabata Inés Romero-Brey Charlotta Funaya Nicole L. Schieber Yu Qiang Marie Bartenschlager Stephanie Kallis Christian Ritter Karl Rohr Yannick Schwab Alessia Ruggieri Ralf Bartenschlager Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment Cell Reports |
author_facet |
Ji-Young Lee Mirko Cortese Uta Haselmann Keisuke Tabata Inés Romero-Brey Charlotta Funaya Nicole L. Schieber Yu Qiang Marie Bartenschlager Stephanie Kallis Christian Ritter Karl Rohr Yannick Schwab Alessia Ruggieri Ralf Bartenschlager |
author_sort |
Ji-Young Lee |
title |
Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment |
title_short |
Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment |
title_full |
Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment |
title_fullStr |
Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment |
title_full_unstemmed |
Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment |
title_sort |
spatiotemporal coupling of the hepatitis c virus replication cycle by creating a lipid droplet- proximal membranous replication compartment |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2019-06-01 |
description |
Summary: 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. : Lee et al. visualized likely HCV assembly in live cells and with high resolution. During assembly, HCV structural proteins relocalize to the viral replicase and together induce the wrapping of lipid droplets by ER membranes. These membranes are linked to the viral replication organelle, allowing spatial coordination of replication and assembly. Keywords: replication organelle, double-membrane vesicles, correlative light and electron microscopy, CLEM, HCV, lipid metabolism, virus–host interaction, assembly, lipid droplet, plus-strand RNA virus |
url |
http://www.sciencedirect.com/science/article/pii/S2211124719306928 |
work_keys_str_mv |
AT jiyounglee spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT mirkocortese spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT utahaselmann spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT keisuketabata spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT inesromerobrey spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT charlottafunaya spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT nicolelschieber spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT yuqiang spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT mariebartenschlager spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT stephaniekallis spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT christianritter spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT karlrohr spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT yannickschwab spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT alessiaruggieri spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment AT ralfbartenschlager spatiotemporalcouplingofthehepatitiscvirusreplicationcyclebycreatingalipiddropletproximalmembranousreplicationcompartment |
_version_ |
1724925004340002816 |
spelling |
doaj-b47d6362fb914877b4724dfa3547b7802020-11-25T02:08:50ZengElsevierCell Reports2211-12472019-06-01271236023617.e5Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication CompartmentJi-Young Lee0Mirko Cortese1Uta Haselmann2Keisuke Tabata3Inés Romero-Brey4Charlotta Funaya5Nicole L. Schieber6Yu Qiang7Marie Bartenschlager8Stephanie Kallis9Christian Ritter10Karl Rohr11Yannick Schwab12Alessia Ruggieri13Ralf Bartenschlager14Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany; German Center for Infection Research, Heidelberg Partner Site, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyElectron Microscopy Core Facility, Heidelberg University, 69120 Heidelberg, GermanyCell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, GermanyBiomedical Computer Vision Group, Heidelberg University, BIOQUANT, IPMB, and DKFZ Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyBiomedical Computer Vision Group, Heidelberg University, BIOQUANT, IPMB, and DKFZ Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, GermanyBiomedical Computer Vision Group, Heidelberg University, BIOQUANT, IPMB, and DKFZ Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, GermanyCell Biology and Biophysics Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany; Electron Microscopy Core Facility, European Molecular Biology Laboratory, 69117 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, GermanyDepartment of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany; German Center for Infection Research, Heidelberg Partner Site, Im Neuenheimer Feld 344, 69120 Heidelberg, Germany; Division of Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 242, Heidelberg, Germany; Corresponding authorSummary: 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. : Lee et al. visualized likely HCV assembly in live cells and with high resolution. During assembly, HCV structural proteins relocalize to the viral replicase and together induce the wrapping of lipid droplets by ER membranes. These membranes are linked to the viral replication organelle, allowing spatial coordination of replication and assembly. Keywords: replication organelle, double-membrane vesicles, correlative light and electron microscopy, CLEM, HCV, lipid metabolism, virus–host interaction, assembly, lipid droplet, plus-strand RNA virushttp://www.sciencedirect.com/science/article/pii/S2211124719306928 |