ArticleGastroenterology2015
Phosphatidylinositol 4,5-bisphosphate is an HCV NS5A ligand and mediates replication of the viral genome.
Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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
24 citing papers in PubMed, 42 citations in OpenAlex.
- Phospholipid-driven conformational switching of HCV NS5A links protein folding to replication membrane remodeling.Science advances · 2026Article
- SCARF Genes in COVID-19 and Kidney Disease: A Path to Comorbidity-Specific Therapies.International journal of molecular sciences · 2023Review
- Article
- Regulatory Role of Phospholipids in Hepatitis C Virus Replication and Protein Function.Pathogens (Basel, Switzerland) · 2022Review
- Identification of a Proline-Kinked Amphipathic α-Helix Downstream from the Methyltransferase Domain of a Potexvirus Replicase and Its Role in Virus Replication and Perinuclear Complex Formation.Journal of virology · 2021Article
- Hepatitis C Virus Uses Host Lipids to Its Own Advantage.Metabolites · 2021Review
- Phosphatidylinositol 3-Phosphate Mediates the Establishment of Infectious Bursal Disease Virus Replication Complexes in Association with Early Endosomes.Journal of virology · 2021Article
- Exploiting Connections for Viral Replication.Frontiers in cell and developmental biology · 2021Article
- Materials science approaches in the development of broad-spectrum antiviral therapies.Nature materials · 2020Article
- Host factor prioritization for pan-viral genetic perturbation screens using random intercept models and network propagation.PLoS computational biology · 2020Article
- Nir2 Is an Effector of VAPs Necessary for Efficient Hepatitis C Virus Replication and Phosphatidylinositol 4-Phosphate Enrichment at the Viral Replication Organelle.Journal of virology · 2019Article
- Host Lipids in Positive-Strand RNA Virus Genome Replication.Frontiers in microbiology · 2019Review
- Hijacking of multiple phospholipid biosynthetic pathways and induction of membrane biogenesis by a picornaviral 3CD protein.PLoS pathogens · 2018Article
- The RNA-Binding Site of Poliovirus 3C Protein Doubles as a Phosphoinositide-Binding Domain.Structure (London, England : 1993) · 2017Article
- Quantitative Evaluation of Viral Protein Binding to Phosphoinositide Receptors and Pharmacological Inhibition.Analytical chemistry · 2017Article
- Viral rewiring of cellular lipid metabolism to create membranous replication compartments.Current opinion in cell biology · 2017Review
- PIP-on-a-chip: A Label-free Study of Protein-phosphoinositide Interactions.Journal of visualized experiments : JoVE · 2017Article
- PI3K/SHIP2/PTEN pathway in cell polarity and hepatitis C virus pathogenesis.World journal of hepatology · 2017Review
- (+) RNA virus replication compartments: a safe home for (most) viral replication.Current opinion in microbiology · 2016Review
- Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIβ.Journal of medicinal chemistry · 2016Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsPhosphoinositides (PIs) bind and regulate localization of proteins via a variety of structural motifs. PI 4,5-bisphosphate (PI[4,5]P2) interacts with and modulates the function of several proteins involved in intracellular vesicular membrane trafficking. We investigated interactions between PI(4,5)P2 and hepatitis C virus (HCV) nonstructural protein 5A (NS5A) and effects on the viral life cycle.
methodsWe used a combination of quartz crystal microbalance, circular dichroism, molecular genetics, and immunofluorescence to study specific binding of PI(4,5)P2 by the HCV NS5A protein. We evaluated the effects of PI(4,5)P2 on the function of NS5A by expressing wild-type or mutant forms of Bart79I or FL-J6/JFH-5'C19Rluc2AUbi21 RNA in Huh7 cells. We also studied the effects of strategies designed to inhibit PI(4,5)P2 on HCV replication in these cells.
resultsThe N-terminal amphipathic helix of NS5A bound specifically to PI(4,5)P2, inducing a conformational change that stabilized the interaction between NS5A and TBC1D20, which is required for HCV replication. A pair of positively charged residues within the amphipathic helix (the basic amino acid PI(4,5)P2 pincer domain) was required for PI(4,5)P2 binding and replication of the HCV-RNA genome. A similar motif was found to be conserved across all HCV isolates, as well as amphipathic helices of many pathogens and apolipoproteins.
conclusionsPI(4,5)P2 binds to HCV NS5A to promote replication of the viral RNA genome in hepatocytes. Strategies to disrupt this interaction might be developed to inhibit replication of HCV and other viruses.
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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.