ArticleJournal of virology2012
Evaluation of phosphatidylinositol-4-kinase IIIα as a hepatitis C virus drug target.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 59 citations in OpenAlex.
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Case Report: Prenatal diagnosis of gastrointestinal defects and immunodeficiency syndrome caused by compound heterozygous mutations in TTC7A gene.Frontiers in immunology · 2025Article
- Two Novel Variants inNeurology. Genetics · 2024Article
- Postnatal Development and Maintenance of Functional Pituitary Gonadotrophs Is Dependent on PI4-Kinase A.Endocrinology · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Structure-function analysis of enterovirus protease 2A in complex with its essential host factor SETD3.Nature communications · 2022Article
- LIPID transfer proteins regulate store-operated calcium entry via control of plasma membrane phosphoinositides.Cell calcium · 2022Article
- Biallelic PI4KA variants cause neurological, intestinal and immunological disease.Brain : a journal of neurology · 2021Article
- Components of the phosphatidylserine endoplasmic reticulum to plasma membrane transport mechanism as targets for KRAS inhibition in pancreatic cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics.The Biochemical journal · 2020Review
- Drug Screen Identifies Leflunomide for Treatment of Inflammatory Bowel Disease Caused by TTC7A Deficiency.Gastroenterology · 2020Article
- In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects?Journal of neurodevelopmental disorders · 2019Review
- TTC7A: Steward of Intestinal Health.Cellular and molecular gastroenterology and hepatology · 2019Review
- Histone Deacetylase 3 Inhibitor Suppresses Hepatitis C Virus Replication by Regulating Apo-A1 and LEAP-1 Expression.Virologica Sinica · 2018Article
- A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis.Cell reports · 2018Article
- Bialellic Mutations in Tetratricopeptide Repeat Domain 7A (TTC7A) Cause Common Variable Immunodeficiency-Like Phenotype with Enteropathy.Journal of clinical immunology · 2017Article
- Viral rewiring of cellular lipid metabolism to create membranous replication compartments.Current opinion in cell biology · 2017Review
- Tyrphostin AG1478 Inhibits Encephalomyocarditis Virus and Hepatitis C Virus by Targeting Phosphatidylinositol 4-Kinase IIIα.Antimicrobial agents and chemotherapy · 2016Article
- Purine analogs as phosphatidylinositol 4-kinase IIIβ inhibitors.Bioorganic & medicinal chemistry letters · 2016Article
- Targeting host lipid synthesis and metabolism to inhibit dengue and hepatitis C viruses.Antiviral research · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphatidylinositol-4-kinase IIIα (PI4KIIIα) is an essential host cell factor for hepatitis C virus (HCV) replication. An N-terminally truncated 130-kDa form was used to reconstitute an in vitro biochemical lipid kinase assay that was optimized for small-molecule compound screening and identified potent and specific inhibitors. Cell culture studies with PI4KIIIα inhibitors demonstrated that the kinase activity was essential for HCV RNA replication. Two PI4KIIIα inhibitors were used to select cell lines harboring HCV replicon mutants with a 20-fold loss in sensitivity to the compounds. Reverse genetic mapping isolated an NS4B-NS5A segment that rescued HCV RNA replication in PIK4IIIα-deficient cells. HCV RNA replication occurs on specialized membranous webs, and this study with PIK4IIIα inhibitor-resistant mutants provides a genetic link between NS4B/NS5A functions and PI4-phosphate lipid metabolism. A comprehensive assessment of PI4KIIIα as a drug target included its evaluation for pharmacologic intervention in vivo through conditional transgenic murine lines that mimic target-specific inhibition in adult mice. Homozygotes that induce a knockout of the kinase domain or knock in a single amino acid substitution, kinase-defective PI4KIIIα, displayed a lethal phenotype with a fairly widespread mucosal epithelial degeneration of the gastrointestinal tract. This essential host physiologic role raises doubt about the pursuit of PI4KIIIα inhibitors for treatment of chronic HCV infection.
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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.