ArticleProceedings of the National Academy of Sciences of the United States of America2009
Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replication.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 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.
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Who cites it
217 citing papers in PubMed, 341 citations in OpenAlex.
- Reciprocal control of viral infection and phosphoinositide dynamics.FEBS letters · 2026Review
- Phosphatidylserine and RhoB connect PI4P and PA metabolism to maintain plasma membrane identity.The Journal of cell biology · 2026Article
- Development of an inhibitory TTC7B selective nanobody that blocks EFR3 recruitment of PI4KA.The Journal of biological chemistry · 2025Article
- Development of an inhibitory TTC7B selective nanobody that blocks EFR3 recruitment of PI4KA.bioRxiv : the preprint server for biology · 2025Article
- Phosphatidylserine and RhoB connect phosphatidylinositol 4-phosphate and phosphatidic acid metabolism at the plasma membrane.bioRxiv : the preprint server for biology · 2025Article
- Plant negative-strand RNA virus phosphoprotein condensates exploit host trafficking and lipid synthesis for viral factory assembly.Science advances · 2025Article
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- HCV NS3/4A protease relocalizes CCTα to viral replication sites, enhancing phosphatidylcholine synthesis and viral replication.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inositol metabolism as a broad-spectrum antiviral target.Frontiers in microbiology · 2025Review
- Hepatitis C Virus NS5A Activates Mitophagy Through Cargo Receptor and Phagophore Formation.Pathogens (Basel, Switzerland) · 2024Article
- Molecular basis for plasma membrane recruitment of PI4KA by EFR3.Science advances · 2024Article
- Molecular basis for plasma membrane recruitment of PI4KA by EFR3.bioRxiv : the preprint server for biology · 2024Article
- Diacylglycerol O-acyltransferase 2, a Novel Target of Flavivirus NS2B3 Protease, Promotes Zika Virus Replication by Regulating Lipid Droplet Formation.Research (Washington, D.C.) · 2024Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- NS5A domain I antagonises PKR to facilitate the assembly of infectious hepatitis C virus particles.PLoS pathogens · 2023Article
- Article
- Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection.Journal of the Royal Society, Interface · 2021Article
- Courier service for phosphatidylinositol: PITPs deliver on demand.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021Review
- The chemistry and biology of phosphatidylinositol 4-phosphate at the plasma membrane.Bioorganic & medicinal chemistry · 2021Review
- Exploiting Connections for Viral Replication.Frontiers in cell and developmental biology · 2021Article
157 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) reorganizes cellular membranes to establish sites of replication. The required host pathways and the mechanism of cellular membrane reorganization are poorly characterized. Therefore, we interrogated a customized small interfering RNA (siRNA) library that targets 140 host membrane-trafficking genes to identify genes required for both HCV subgenomic replication and infectious virus production. We identified 7 host cofactors of viral replication, including Cdc42 and Rock2 (actin polymerization), EEA1 and Rab5A (early endosomes), Rab7L1, and PI3-kinase C2gamma and PI4-kinase IIIalpha (phospholipid metabolism). Studies of drug inhibitors indicate actin polymerization and phospholipid kinase activity are required for HCV replication. We found extensive co-localization of the HCV replicase markers NS5A and double-stranded RNA with Rab5A and partial co-localization with Rab7L1. PI4K-IIIalpha co-localized with NS5A and double-stranded RNA in addition to being present in detergent-resistant membranes containing NS5A. In a comparison of type II and type III PI4-kinases, PI4Ks were not required for HCV entry, and only PI4K-IIIalpha was required for HCV replication. Although PI4K-IIIalpha siRNAs decreased HCV replication and virus production by almost 100%, they had no effect on initial HCV RNA translation, suggesting that PI4K-IIIalpha functions at a posttranslational stage. Electron microscopy identified the presence of membranous webs, which are thought to be the site of HCV replication, in HCV-infected cells. Pretreatment with PI4K-IIIalpha siRNAs greatly reduced the accumulation of these membranous web structures in HCV-infected cells. We propose that PI4K-IIIalpha plays an essential role in membrane alterations leading to the formation of HCV replication complexes.
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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.