ArticleJournal of virology2009
Structural and functional analysis of hepatitis C virus strain JFH1 polymerase.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed.
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Positive strand RNA viruses differ in the constraints they place on the folding of their negative strand.RNA (New York, N.Y.) · 2022Article
- Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication.International journal of molecular sciences · 2020Article
- Evidence for Internal Initiation of RNA Synthesis by the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5BJournal of virology · 2019Article
- Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development.Medical microbiology and immunology · 2019Review
- Hepatitis C virus-induced prion protein expression facilitates hepatitis C virus replication.Virologica Sinica · 2017Article
- 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
- Hepatitis C virus RNA replication and assembly: living on the fat of the land.Cell host & microbe · 2014Review
- Initiation of RNA synthesis by the hepatitis C virus RNA-dependent RNA polymerase is affected by the structure of the RNA template.Biochemistry · 2014Article
- 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
- Mapping of functional domains of the lipid kinase phosphatidylinositol 4-kinase type III alpha involved in enzymatic activity and hepatitis C virus replication.Journal of virology · 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
- The molecular and structural basis of advanced antiviral therapy for hepatitis C virus infection.Nature reviews. Microbiology · 2013Review
- The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A.PLoS pathogens · 2013Article
- Article
- Hepatitis C virus RNA replication.Current topics in microbiology and immunology · 2013Review
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis C virus (HCV) isolate JFH1 represents the only cloned wild-type sequence capable of efficient replication in cell culture, as well as in chimpanzees. Previous reports have pointed to the viral polymerase NS5B as a major determinant for efficient replication of this isolate. To understand the underlying mechanisms, we expressed and purified NS5B of JFH1 and of the closely related isolate J6, which replicates below the limit of detection in cell culture. The JFH1 enzyme exhibited a 5- to 10-fold-higher specific activity in vitro, consistent with the polymerase activity itself contributing to efficient replication of JFH1. The higher in vitro activity of the JFH1 enzyme was not due to increased RNA binding, elongation rate, or processivity of the polymerase but to higher initiation efficiency. By using homopolymeric and heteropolymeric templates, we found that purified JFH1 NS5B was significantly more efficient in de novo initiation of RNA synthesis than the J6 counterpart, particularly at low GTP concentrations, probably representing an important prerequisite for the rapid replication kinetics of JFH1. Furthermore, we solved the crystal structure of JFH1 NS5B, which displays a very closed conformation that is expected to facilitate de novo initiation. Structural analysis shows that this closed conformation is stabilized by a sprinkle of substitutions that together promote extra hydrophobic interactions between the subdomains "thumb" and "fingers." These analyses provide deeper insights into the initiation of HCV RNA synthesis and might help to establish more efficient cell culture models for HCV using alternative isolates.
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