Spatiotemporal Coupling of the Hepatitis C Virus Replication Cycle by Creating a Lipid Droplet- Proximal Membranous Replication Compartment

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 retic...

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Bibliographic Details
Published in:	Cell reports (Cambridge) 2019-06, Vol.27 (12), p.3602-3617.e5
Main Authors:	Lee, Ji-Young, Cortese, Mirko, Haselmann, Uta, Tabata, Keisuke, Romero-Brey, Inés, Funaya, Charlotta, Schieber, Nicole L., Qiang, Yu, Bartenschlager, Marie, Kallis, Stephanie, Ritter, Christian, Rohr, Karl, Schwab, Yannick, Ruggieri, Alessia, Bartenschlager, Ralf
Format:	Article
Language:	eng
Subjects:	assembly CLEM correlative light and electron microscopy double-membrane vesicles HCV lipid droplet lipid metabolism plus-strand RNA virus replication organelle virus–host interaction
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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. [Display omitted] •Established live cell imaging system to visualize HCV assembly events•Determined conditions for recruitment of viral proteins to putative assembly sites•HCV induces wrapping of lipid droplets by ER membranes at putative assembly sites•Wrapping membranes are linked to double membrane vesicles, the HCV replication sites 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.
ISSN:	2211-1247 2211-1247