ArticlePloS one2011
A cell-based assay for RNA synthesis by the HCV polymerase reveals new insights on mechanism of polymerase inhibitors and modulation by NS5A.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Highs and Lows in Calicivirus Reverse Genetics.Viruses · 2024Review
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- Functional genetic variants of the IFN-λ3 (IL28B) gene and transcription factor interactions on its promoter.Cytokine · 2021Article
- Persistent Innate Immune Stimulation Results in IRF3-Mediated but Caspase-Independent Cytostasis.Viruses · 2020Article
- Crystal Structure of Classical Swine Fever Virus NS5B Reveals a Novel N-Terminal Domain.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
- A screen for novel hepatitis C virus RdRp inhibitor identifies a broad-spectrum antiviral compound.Scientific reports · 2017Article
- NOD1 Participates in the Innate Immune Response Triggered by Hepatitis C Virus Polymerase.Journal of virology · 2016Article
- An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection.Methods in molecular biology (Clifton, N.J.) · 2016Article
- The juxtamembrane sequence of the Hepatitis C virus polymerase can affect RNA synthesis and inhibition by allosteric polymerase inhibitors.Virus genes · 2015Article
- Hepatitis C virus RNA replication depends on specific cis- and trans-acting activities of viral nonstructural proteins.PLoS pathogens · 2015Article
- The hepatitis C virus core protein can modulate RNA-dependent RNA synthesis by the 2a polymerase.Virus research · 2014Article
- The classic swine fever virus (CSFV) core protein can enhance de novo-initiated RNA synthesis by the CSFV polymerase NS5B.Virus genes · 2014Article
- Review
- Restoration of the activated Rig-I pathway in hepatitis C virus (HCV) replicon cells by HCV protease, polymerase, and NS5A inhibitors in vitro at clinically relevant concentrations.Antimicrobial agents and chemotherapy · 2013Article
- Lymphotoxin signaling is initiated by the viral polymerase in HCV-linked tumorigenesis.PLoS pathogens · 2013Article
- Article
- Article
- Hepatitis C virus RNA replication.Current topics in microbiology and immunology · 2013Review
- Hepatitis C virus NS5B and host cyclophilin A share a common binding site on NS5A.The Journal of biological chemistry · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
RNA synthesis by the genotype 1b hepatitis C virus (HCV) polymerase (NS5B) transiently expressed in Human embryonic kidney 293T cells or liver hepatocytes was found to robustly stimulate RIG-I-dependent luciferase production from the interferon β promoter in the absence of exogenously provided ligand. This cell-based assay, henceforth named the 5BR assay, could be used to examine HCV polymerase activity in the absence of other HCV proteins. Mutations that decreased de novo initiated RNA synthesis in biochemical assays decreased activation of RIG-I signaling. In addition, NS5B that lacks the C-terminal transmembrane helix but remains competent for RNA synthesis could activate RIG-I signaling. The addition of cyclosporine A to the cells reduced luciferase levels without affecting agonist-induced RIG-I signaling. Furthermore, non-nucleoside inhibitor benzothiadiazines (BTDs) that bind within the template channel of the 1b NS5B were found to inhibit the readout from the 5BR assay. Mutation M414T in NS5B that rendered the HCV replicon resistant to BTD was also resistant to BTDs in the 5BR assay. Co-expression of the HCV NS5A protein along with NS5B and RIG-I was found to inhibit the readout from the 5BR assay. The inhibition by NS5A was decreased with the removal of the transmembrane helix in NS5B. Lastly, NS5B from all six major HCV genotypes showed robust activation of RIG-I in the 5BR assay. In summary, the 5BR assay could be used to validate inhibitors of the HCV polymerase as well as to elucidate requirements for HCV-dependent RNA synthesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.