ArticlePLoS pathogens2015
Hepatitis C virus RNA replication depends on specific cis- and trans-acting activities of viral nonstructural proteins.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
23 citing papers in PubMed, 31 citations in OpenAlex.
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Hepatitis C Virus 5'UTR Sequences That Bind eIF3 and Ribosomal 40S Subunits Confer Stimulation of Minus-Strand RNA Synthesis.International journal of molecular sciences · 2026Article
- A ribosome-bound pseudoknot in the HCV coding region stimulates viral growth by tuning viral translation.Cell reports · 2026Article
- SARS-CoV-2 polyprotein expression and the induction of double-membrane vesicles.Journal of virology · 2025Article
- Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies.PLoS computational biology · 2023Article
- Article
- Characterization of a multipurpose NS3 surface patch coordinating HCV replicase assembly and virion morphogenesis.PLoS pathogens · 2022Article
- Mathematical modeling of plus-strand RNA virus replication to identify broad-spectrum antiviral treatment strategies.bioRxiv : the preprint server for biology · 2022Article
- TheJournal of virology · 2022Article
- Hepatitis C Viral Replication Complex.Viruses · 2021Review
- Hepatitis C virus NS3-4A protease regulates the lipid environment for RNA replication by cleaving host enzyme 24-dehydrocholesterol reductase.The Journal of biological chemistry · 2020Article
- Evidence for Internal Initiation of RNA Synthesis by the Hepatitis C Virus RNA-Dependent RNA Polymerase NS5BJournal of virology · 2019Article
- Targeting HCV polymerase: a structural and dynamic perspective into the mechanism of selective covalent inhibition.RSC advances · 2018Article
- Intracellular Hepatitis C Virus Modeling Predicts Infection Dynamics and Viral Protein Mechanisms.Journal of virology · 2018Article
- Article
- IRE1α promotes viral infection by conferring resistance to apoptosis.Science signaling · 2017Article
- Functional RNA structures throughout the Hepatitis C Virus genome.Current opinion in virology · 2017Review
- Affinity Purification of the Hepatitis C Virus Replicase Identifies Valosin-Containing Protein, a Member of the ATPases Associated with Diverse Cellular Activities Family, as an Active Virus Replication Modulator.Journal of virology · 2016Article
- My Cousin, My Enemy: quasispecies suppression of drug resistance.Current opinion in virology · 2016Review
- Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.Journal of virology · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Many positive-strand RNA viruses encode genes that can function in trans, whereas other genes are required in cis for genome replication. The mechanisms underlying trans- and cis-preferences are not fully understood. Here, we evaluate this concept for hepatitis C virus (HCV), an important cause of chronic liver disease and member of the Flaviviridae family. HCV encodes five nonstructural (NS) genes that are required for RNA replication. To date, only two of these genes, NS4B and NS5A, have been trans-complemented, leading to suggestions that other replicase genes work only in cis. We describe a new quantitative system to measure the cis- and trans-requirements for HCV NS gene function in RNA replication and identify several lethal mutations in the NS3, NS4A, NS4B, NS5A, and NS5B genes that can be complemented in trans, alone or in combination, by expressing the NS3-5B polyprotein from a synthetic mRNA. Although NS5B RNA binding and polymerase activities can be supplied in trans, NS5B protein expression was required in cis, indicating that NS5B has a cis-acting role in replicase assembly distinct from its known enzymatic activity. Furthermore, the RNA binding and NTPase activities of the NS3 helicase domain were required in cis, suggesting that these activities play an essential role in RNA template selection. A comprehensive complementation group analysis revealed functional linkages between NS3-4A and NS4B and between NS5B and the upstream NS3-5A genes. Finally, NS5B polymerase activity segregated with a daclatasvir-sensitive NS5A activity, which could explain the synergy of this antiviral compound with nucleoside analogs in patients. Together, these studies define several new aspects of HCV replicase structure-function, help to explain the potency of HCV-specific combination therapies, and provide an experimental framework for the study of cis- and trans-acting activities in positive-strand RNA virus replication more generally.
Indexed as
Identifiers
What OpenQuestion holds
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.