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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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Main Authors: Lee, Ji Young (Author) , Cortese, Mirko (Author) , Haselmann, Uta (Author) , Tabata, Keisuke (Author) , Romero-Brey, Inés (Author) , Funaya, Charlotta (Author) , Schieber, Nicole L. (Author) , Qiang, Yu (Author) , Bartenschlager, Marie (Author) , Kallis, Stephanie (Author) , Ritter, Christian (Author) , Rohr, Karl (Author) , Schwab, Yannick (Author) , Ruggieri, Alessia (Author) , Bartenschlager, Ralf (Author)
Format: Article (Journal)
Language:English
Published: 18 June 2019
In: Cell reports
Year: 2019, Volume: 27, Issue: 12, Pages: 3602-3617.e5
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.05.063
Online Access:Verlag, Volltext: https://doi.org/10.1016/j.celrep.2019.05.063
Verlag: http://www.sciencedirect.com/science/article/pii/S2211124719306928
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Author Notes: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
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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.
Item Description:Gesehen am 15.01.2020
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2019.05.063

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