Regulation of the hepatitis C virus RNA replicase by endogenous lipid peroxidation
Daisuke Yamane,David R. McGivern,Eliane Wauthier,Min Kyung Yi,Victoria J. Madden,Christoph Welsch,Iris Antes,Yahong Wen,Pauline E. Chugh,Charles E. McGee,Douglas G. Widman,Ichiro Misumi,Sibali Bandyopadhyay,Seungtaek Kim,Tetsuro Shimakami,Tsunekazu Oikawa,Jason K. Whitmire,Mark T. Heise,Dirk P. Dittmer,C. Cheng Kao,Stuart M. Pitson,Alfred H. Merrill,Lola M. Reid,Stanley M. Lemon +23 more
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TLDR
It is shown that multiple hepatitis C virus genotypes are exquisitely sensitive to oxidative membrane damage, a property distinguishing them from other pathogenic RNA viruses, and that the typical, wild-type HCV replicase is uniquely regulated by lipid peroxidation.Abstract:
Oxidative tissue injury often accompanies viral infection, yet there is little understanding of how it influences virus replication. We show that multiple hepatitis C virus (HCV) genotypes are exquisitely sensitive to oxidative membrane damage, a property distinguishing them from other pathogenic RNA viruses. Lipid peroxidation, regulated in part through sphingosine kinase-2, severely restricts HCV replication in Huh-7 cells and primary human hepatoblasts. Endogenous oxidative membrane damage lowers the 50% effective concentration of direct-acting antivirals in vitro, suggesting critical regulation of the conformation of the NS3-4A protease and the NS5B polymerase, membrane-bound HCV replicase components. Resistance to lipid peroxidation maps genetically to transmembrane and membrane-proximal residues within these proteins and is essential for robust replication in cell culture, as exemplified by the atypical JFH1 strain of HCV. Thus, the typical, wild-type HCV replicase is uniquely regulated by lipid peroxidation, providing a mechanism for attenuating replication in stressed tissue and possibly facilitating long-term viral persistence.read more
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N6-Methyladenosine in Flaviviridae Viral RNA Genomes Regulates Infection.
Nandan S. Gokhale,Alexa B. R. McIntyre,Michael J. McFadden,Allison E. Roder,Edward M. Kennedy,Jorge Gandara,Sharon E. Hopcraft,Kendra M. Quicke,Kendra M. Quicke,Christine Vazquez,Jason R. Willer,Olga Ilkayeva,Brittany A. Law,Christopher L. Holley,Mariano A. Garcia-Blanco,Mariano A. Garcia-Blanco,Matthew J. Evans,Mehul S. Suthar,Mehul S. Suthar,Shelton S. Bradrick,Christopher E. Mason,Stacy M. Horner +21 more
TL;DR: It is demonstrated that m6A modulates infection by hepatitis C virus (HCV) and is identified as a conserved regulatory mark across Flaviviridae genomes.
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The history of hepatitis C virus (HCV): Basic research reveals unique features in phylogeny, evolution and the viral life cycle with new perspectives for epidemic control
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Ultrastructure of the replication sites of positive-strand RNA viruses
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SEC14L2 enables pan-genotype HCV replication in cell culture
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TL;DR: Mechanistic studies suggest that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation, and provides a foundation for development of in vitro replication systems for all HCV isolates.
References
More filters
Journal ArticleDOI
VMD: Visual molecular dynamics
TL;DR: VMD is a molecular graphics program designed for the display and analysis of molecular assemblies, in particular biopolymers such as proteins and nucleic acids, which can simultaneously display any number of structures using a wide variety of rendering styles and coloring methods.
Journal ArticleDOI
THE USE OF LEAD CITRATE AT HIGH pH AS AN ELECTRON-OPAQUE STAIN IN ELECTRON MICROSCOPY
TL;DR: The stain reported here differs from previous alkaline lead stains in that the chelating agent, citrate, is in sufficient excess to sequester all lead present, and is less likely to contaminate sections.
Journal ArticleDOI
Production of infectious hepatitis C virus in tissue culture from a cloned viral genome
Takaji Wakita,Thomas Pietschmann,Takanobu Kato,Takanobu Kato,Tomoko Date,Michiko Miyamoto,Zijiang Zhao,Krishna K. Murthy,Anja Habermann,Hans-Georg Kräusslich,Masashi Mizokami,Ralf Bartenschlager,T. Jake Liang +12 more
TL;DR: It is shown that the JFH1 genome replicates efficiently and supports secretion of viral particles after transfection into a human hepatoma cell line (Huh7) and provides a powerful tool for studying the viral life cycle and developing antiviral strategies.
Journal ArticleDOI
Complete Replication of Hepatitis C Virus in Cell Culture
Brett D. Lindenbach,Brett D. Lindenbach,Brett D. Lindenbach,Matthew J. Evans,Matthew J. Evans,Matthew J. Evans,Andrew J. Syder,Andrew J. Syder,Andrew J. Syder,Benno Wölk,Benno Wölk,Benno Wölk,Timothy L. Tellinghuisen,Timothy L. Tellinghuisen,Timothy L. Tellinghuisen,Christopher C. Liu,Christopher C. Liu,Christopher C. Liu,Toshiaki Maruyama,Toshiaki Maruyama,Toshiaki Maruyama,Richard O. Hynes,Richard O. Hynes,Richard O. Hynes,Dennis R. Burton,Dennis R. Burton,Dennis R. Burton,Jane A. McKeating,Jane A. McKeating,Jane A. McKeating,Charles M. Rice,Charles M. Rice,Charles M. Rice +32 more
TL;DR: A full-length HCV genome that replicates and produces virus particles that are infectious in cell culture (HCVcc) is described, suggesting that this in vitro system will aid in the search for improved antiviral compounds.
Journal ArticleDOI
Robust hepatitis C virus infection in vitro
Jin Zhong,Pablo Gastaminza,Guofeng Cheng,Sharookh B. Kapadia,Takanobu Kato,Dennis R. Burton,Stefan Wieland,Susan L. Uprichard,Takaji Wakita,Francis V. Chisari +9 more
TL;DR: A simple yet robust HCV cell culture infection system based on the HCV JFH-1 molecular clone and Huh-7-derived cell lines that allows the production of virus that can be efficiently propagated in tissue culture is reported.
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