ArticleJournal of virology2014
Hepatitis C virus RNA replication and virus particle assembly require specific dimerization of the NS4A protein transmembrane domain.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 25 citations in OpenAlex.
- Integrated deep learning and multi-scale modeling for the discovery of pan-genotypic HCV NS5B polymerase inhibitors.Molecular diversity · 2026Article
- Characterization of a multipurpose NS3 surface patch coordinating HCV replicase assembly and virion morphogenesis.PLoS pathogens · 2022Article
- Production of an Active, Human Membrane Protein inInternational journal of molecular sciences · 2022Article
- Experimental determination and data-driven prediction of homotypic transmembrane domain interfaces.Computational and structural biotechnology journal · 2020Article
- Article
- Hepatitis C Virus Infection Is Inhibited by a Noncanonical Antiviral Signaling Pathway Targeted by NS3-NS4A.Journal of virology · 2019Article
- Determination of Critical Requirements for Classical Swine Fever Virus NS2-3-Independent Virion Formation.Journal of virology · 2019Article
- Adaptive mutation F772S-enhanced p7-NS4A cooperation facilitates the assembly and release of hepatitis C virus and is associated with lipid droplet enlargement.Emerging microbes & infections · 2018Article
- HCV NS5A dimer interface residues regulate HCV replication by controlling its self-interaction, hyperphosphorylation, subcellular localization and interaction with cyclophilin A.PLoS pathogens · 2018Article
- Hepatitis C Virus Genotype 1 to 6 Protease Inhibitor Escape Variants: In Vitro Selection, Fitness, and Resistance Patterns in the Context of the Infectious Viral Life Cycle.Antimicrobial agents and chemotherapy · 2016Article
- Polyprotein-Driven Formation of Two Interdependent Sets of Complexes Supporting Hepatitis C Virus Genome Replication.Journal of virology · 2015Article
- Hepatitis C virus RNA replication depends on specific cis- and trans-acting activities of viral nonstructural proteins.PLoS pathogens · 2015Article
- The interaction between the hepatitis C proteins NS4B and NS5A is involved in viral replication.Virology · 2015Article
- Hepatitis C virus RNA replication and assembly: living on the fat of the land.Cell host & microbe · 2014Review
- The linker region of NS3 plays a critical role in the replication and infectivity of hepatitis C virus.Journal of virology · 2014Article
- Regulation of the hepatitis C virus RNA replicase by endogenous lipid peroxidation.Nature medicine · 2014Article
- The elusive function of the hepatitis C virus p7 protein.Virology · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) NS4A is a single-pass transmembrane (TM) protein essential for viral replication and particle assembly. The sequence of the NS4A TM domain is highly conserved, suggesting that it may be important for protein-protein interactions. To test this hypothesis, we measured the potential dimerization of the NS4A TM domain in a well-characterized two-hybrid TM protein interaction system. The NS4A TM domain exhibited a strong homotypic interaction that was comparable in affinity to glycophorin A, a well-studied human blood group antigen that forms TM homodimers. Several mutations predicted to cluster on a common surface of the NS4A TM helix caused significant reductions in dimerization, suggesting that these residues form an interface for NS4A dimerization. Mutations in the NS4A TM domain were further examined in the JFH-1 genotype 2a replicon system; importantly, all mutations that destabilized NS4A dimers also caused defects in RNA replication and/or virus assembly. Computational modeling of NS4A TM interactions suggests a right-handed dimeric interaction of helices with an interface that is consistent with the mutational effects. Furthermore, defects in NS4A oligomerization and virus particle assembly of two mutants were rescued by NS4A A15S, a TM mutation recently identified through forward genetics as a cell culture-adaptive mutation. Together, these data provide the first example of a functionally important TM dimer interface within an HCV nonstructural protein and reveal a fundamental role of the NS4A TM domain in coordinating HCV RNA replication and virus particle assembly.
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.