Journal ArticleDOI
Efficient initiation of HCV RNA replication in cell culture.
TLDR
This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication and identifies multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro.Abstract:
Hepatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. We report the identification of multiple independent adaptive mutations that cluster in the HCV nonstructural protein NS5A and confer increased replicative ability in vitro. Among these adaptive mutations were a single amino acid substitution that allowed HCV RNA replication in 10% of transfected hepatoma cells and a deletion of 47 amino acids encompassing the interferon (IFN) sensitivity determining region (ISDR). Independent of the ISDR, IFN-α rapidly inhibited HCV RNA replication in vitro. This work establishes a robust, cell-based system for genetic and functional analyses of HCV replication.read more
Citations
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Journal ArticleDOI
Hepatitis C Virus Infection
Georg M. Lauer,Bruce D. Walker +1 more
TL;DR: The institution of blood-screening measures in developed countries has decreased the risk of transfusion-associated hepatitis to a negligible level, but new cases continue to occur mainly as a result of injection-drug use and, to a lesser degree, through other means of percutaneous or mucous-membrane exposure.
Journal ArticleDOI
Antiviral Actions of Interferons
TL;DR: Tremendous progress has been made in understanding the molecular basis of the antiviral actions of interferons (IFNs), as well as strategies evolved by viruses to antagonize the actions of IFNs.
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.
Flaviviridae :T he Viruses and Their Replication
TL;DR: The present research attacked the Flavivirus infection through two mechanisms: Membrane Reorganization and the Compartmentalization and Assembly and Release of Particles from Flaviv virus-infected Cells and Host Resistance to Flaviviral Infection.
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.
References
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Journal ArticleDOI
Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell Line
TL;DR: This work defines the structure of HCV replicons functional in cell culture and provides the basis for a long-sought cellular system that should allow detailed molecular studies ofHCV and the development of antiviral drugs.
Journal ArticleDOI
Mutations in the Nonstructural Protein 5a Gene and Response to Interferon in Patients with Chronic Hepatitis C Virus 1b Infection
Nobuyuki Enomoto,Ikuo Sakuma,Yasuhiro Asahina,Masayuki Kurosaki,Takeshi Murakami,Chikara Yamamoto,Yuki Ogura,Namiki Izumi,Fumiaki Marumo,Chifumi Sato +9 more
TL;DR: In patients with chronic HCV-1b infection, there is a substantial correlation between responses to interferon and mutations in the NS5A gene.
Journal ArticleDOI
Genetic Heterogeneity of Hepatitis C Virus: Quasispecies and Genotypes
TL;DR: It is revealed that HCV exists as multiple, distinct genotypes, and phylogenetic analyses of complete and partial nucleotide sequences from isolates that represent all published variants of HCV revealed that the genetic relatedness among some of the genotypes was not equivalent in the different gene regions.
Journal ArticleDOI
Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein
Michael Gale,Marcus J. Korth,Norina M. Tang,Seng Lai Tan,Deborah A. Hopkins,Thomas E. Dever,Stephen J. Polyak,David R. Gretch,Michael G. Katze +8 more
TL;DR: It is reported that NS5A represses PKR through a direct interaction with the protein kinase catalytic domain and that both PKR repression and interaction requires the ISDR, suggesting inactivation of PKR may be one mechanism by which HCV avoids the antiviral effects of IFN.
Journal ArticleDOI
Transmission of Hepatitis C by Intrahepatic Inoculation with Transcribed RNA
Alexander A. Kolykhalov,Eugene Agapov,Eugene Agapov,Keril J. Blight,Keril J. Blight,Kathleen Mihalik,Kathleen Mihalik,Stephen M. Feinstone,Stephen M. Feinstone,Charles M. Rice,Charles M. Rice +10 more
TL;DR: This work defines the structure of a functional HCV genome RNA and proves that HCV alone is sufficient to cause disease.
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Complete Replication of Hepatitis C Virus in Cell Culture
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