ArticleJournal of virology2011
A comprehensive structure-function comparison of hepatitis C virus strain JFH1 and J6 polymerases reveals a key residue stimulating replication in cell culture across genotypes.
Article in Journal of virology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Resistance characterization of hepatitis C virus genotype 2 from Japanese patients treated with ombitasvir and paritaprevir/ritonavir.Journal of medical virology · 2018Trial
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
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- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- TRIM26 is a critical host factor for HCV replication and contributes to host tropism.Science advances · 2021Article
- BK polyomavirus diversity-Why viral variation matters.Reviews in medical virology · 2020Review
- Cell Culture Systems of HCV Using JFH-1 and Other Strains.Cold Spring Harbor perspectives in medicine · 2019Review
- Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development.Medical microbiology and immunology · 2019Review
- The Small-Compound Inhibitor K22 Displays Broad Antiviral Activity against Different Members of the Family Flaviviridae and Offers Potential as a Panviral Inhibitor.Antimicrobial agents and chemotherapy · 2018Article
- NS3 from Hepatitis C Virus Strain JFH-1 Is an Unusually Robust Helicase That Is Primed To Bind and Unwind Viral RNA.Journal of virology · 2018Article
- NMR reveals the intrinsically disordered domain 2 of NS5A protein as an allosteric regulator of the hepatitis C virus RNA polymerase NS5B.The Journal of biological chemistry · 2017Article
- C-Terminal Auto-Regulatory Motif of Hepatitis C Virus NS5B Interacts with Human VAPB-MSP to Form a Dynamic Replication Complex.PloS one · 2016Article
- Article
- DDX60L Is an Interferon-Stimulated Gene Product Restricting Hepatitis C Virus Replication in Cell Culture.Journal of virology · 2015Article
- Novel perspectives for hepatitis A virus therapy revealed by comparative analysis of hepatitis C virus and hepatitis A virus RNA replication.Hepatology (Baltimore, Md.) · 2015Article
- Allosteric inhibitors have distinct effects, but also common modes of action, in the HCV polymerase.Biophysical journal · 2015Article
- Efficient infectious cell culture systems of the hepatitis C virus (HCV) prototype strains HCV-1 and H77.Journal of virology · 2015Article
- Molecular and structural basis for the roles of hepatitis C virus polymerase NS5B amino acids 15, 223, and 321 in viral replication and drug resistance.Antimicrobial agents and chemotherapy · 2014Article
- The hepatitis C virus core protein can modulate RNA-dependent RNA synthesis by the 2a polymerase.Virus research · 2014Article
- Construction of a chimeric hepatitis C virus replicon based on a strain isolated from a chronic hepatitis C patient.Virologica Sinica · 2014Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis C virus (HCV) genotype 2a isolate JFH1 represents the only cloned HCV wild-type sequence capable of efficient replication in cell culture as well as in vivo. Previous reports have pointed to NS5B, the viral RNA-dependent RNA polymerase (RdRp), as a major determinant for efficient replication of this isolate. To understand the contribution of the JFH1 NS5B gene at the molecular level, we aimed at conferring JFH1 properties to NS5B from the closely related J6 isolate. We created intragenotypic chimeras in the NS5B regions of JFH1 and J6 and compared replication efficiency in cell culture and RdRp activity of the purified proteins in vitro, revealing more than three independent mechanisms conferring the role of JFH1 NS5B in efficient RNA replication. Most critical was residue I405 in the thumb domain of the polymerase, which strongly stimulated replication in cell culture by enhancing overall de novo RNA synthesis. A structural comparison of JFH1 and J6 at high resolution indicated a clear correlation of a closed-thumb conformation of the RdRp and the efficiency of the enzyme at de novo RNA synthesis, in accordance with the proposal that I405 enhances de novo initiation. In addition, we identified several residues enhancing replication independent of RdRp activity in vitro. The functional properties of JFH1 NS5B could be restored by a few single-nucleotide substitutions to the J6 isolate. Finally, we were able to enhance the replication efficiency of a genotype 1b isolate with the I405 mutation, indicating that this mechanism of action is conserved across genotypes.
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