TY  - JOUR
A1  - Romero-Brey, Inés
A1  - Merz, Andreas
A1  - Chiramel, Abhilash
A1  - Lee, Ji-Young
A1  - Chlanda, Petr
A1  - Haselman, Uta
A1  - Santarella-Mellwig, Rachel
A1  - Habermann, Anja
A1  - Hoppe, Simone
A1  - Kallis, Stephanie
A1  - Walther, Paul
A1  - Antony, Claude
A1  - Krijnse-Locker, Jacomine
A1  - Bartenschlager, Ralf
T1  - Three-dimensional architecture and biogenesis of membrane structures associated with hepatitis C virus replication
T2  - PLoS pathogens
N2  - All positive strand RNA viruses are known to replicate their genomes in close association with intracellular membranes. In case of the hepatitis C virus (HCV), a member of the family Flaviviridae, infected cells contain accumulations of vesicles forming a membranous web (MW) that is thought to be the site of viral RNA replication. However, little is known about the biogenesis and three-dimensional structure of the MW. In this study we used a combination of immunofluorescence- and electron microscopy (EM)-based methods to analyze the membranous structures induced by HCV in infected cells. We found that the MW is derived primarily from the endoplasmic reticulum (ER) and contains markers of rough ER as well as markers of early and late endosomes, COP vesicles, mitochondria and lipid droplets (LDs). The main constituents of the MW are single and double membrane vesicles (DMVs). The latter predominate and the kinetic of their appearance correlates with kinetics of viral RNA replication. DMVs are induced primarily by NS5A whereas NS4B induces single membrane vesicles arguing that MW formation requires the concerted action of several HCV replicase proteins. Three-dimensional reconstructions identify DMVs as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure. In addition, late in infection multi-membrane vesicles become evident, presumably as a result of a stress-induced reaction. Thus, the morphology of the membranous rearrangements induced in HCV-infected cells resemble those of the unrelated picorna-, corona- and arteriviruses, but are clearly distinct from those of the closely related flaviviruses. These results reveal unexpected similarities between HCV and distantly related positive-strand RNA viruses presumably reflecting similarities in cellular pathways exploited by these viruses to establish their membranous replication factories.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/27729
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-277297
SN  - 1553-7374
SN  - 1553-7366
N1  - © 2012 Romero-Brey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 8
IS  - 12: e1003056
PB  - PLoS
CY  - Lawrence, Kan.
ER  -