ArticleNature2015
SEC14L2 enables pan-genotype HCV replication in cell culture.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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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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.
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Who cites it
66 citing papers in PubMed, 128 citations in OpenAlex.
- SEC14L2 contributes to tumor progression by enhancing USP5-driven RBM3 deubiquitination in pancreatic ductal adenocarcinoma.Oncogene · 2026Article
- A novel dimerization site in non-structural protein 5A of hepatitis C virus regulates viral replication fitness.PLoS pathogens · 2026Article
- Highly replicating hepatitis C virus variants emerge in immunosuppressed patients causing severe disease.Nature communications · 2025Article
- Chronic Hepatitis C in the Direct-Acting Antivirals Era: Carcinogenesis and Clinical Implications.Diseases (Basel, Switzerland) · 2025Review
- Sec14L6 is a phosphoinositide transporter that regulates phosphoinositide homeostasis and biogenesis of lipid droplets.Nature communications · 2025Article
- Detection of Hepatitis C Virus Infection from Patient Sera in Cell Culture Using Semi-Automated Image Analysis.Viruses · 2024Article
- Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes.Journal of virology · 2024Article
- Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection.PloS one · 2024Article
- Full-length sequence analysis of hepatitis C virus genotype 3b strains and development of anJournal of virology · 2023Article
- Challenge Inoculum for Hepatitis C Virus Controlled Human Infection Model.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Role of SEC14-like phosphatidylinositol transfer proteins in membrane identity and dynamics.Frontiers in plant science · 2023Review
- Milestones in the discovery of hepatitis C.World journal of gastroenterology · 2022Review
- A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants.Cell stem cell · 2022Article
- A Hepatitis C virus genotype 1b post-transplant isolate with high replication efficiency in cell culture and its adaptation to infectious virus production in vitro and in vivo.PLoS pathogens · 2022Article
- FADS2-dependent fatty acid desaturation dictates cellular sensitivity to ferroptosis and permissiveness for hepatitis C virus replication.Cell chemical biology · 2022Article
- Cilia-related gene signature in the nasal mucosa correlates with disease severity and outcomes in critical respiratory syncytial virus bronchiolitis.Frontiers in immunology · 2022Article
- A Golgi-derived vesicle potentiates PtdIns4P to PtdIns3P conversion for endosome fission.Nature cell biology · 2021Article
- Review
- Hepatitis C Virus Uses Host Lipids to Its Own Advantage.Metabolites · 2021Review
- A Role for B Cells to Transmit Hepatitis C Virus Infection.Frontiers in immunology · 2021Observational
6 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Since its discovery in 1989, efforts to grow clinical isolates of the hepatitis C virus (HCV) in cell culture have met with limited success. Only the JFH-1 isolate has the capacity to replicate efficiently in cultured hepatoma cells without cell culture-adaptive mutations. We hypothesized that cultured cells lack one or more factors required for the replication of clinical isolates. To identify the missing factors, we transduced Huh-7.5 human hepatoma cells with a pooled lentivirus-based human complementary DNA (cDNA) library, transfected the cells with HCV subgenomic replicons lacking adaptive mutations, and selected for stable replicon colonies. This led to the identification of a single cDNA, SEC14L2, that enabled RNA replication of diverse HCV genotypes in several hepatoma cell lines. This effect was dose-dependent, and required the continuous presence of SEC14L2. Full-length HCV genomes also replicated and produced low levels of infectious virus. Remarkably, SEC14L2-expressing Huh-7.5 cells also supported HCV replication following inoculation with patient sera. Mechanistic studies suggest that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation. This provides a foundation for development of in vitro replication systems for all HCV isolates, creating a useful platform to dissect the mechanisms by which cell culture-adaptive mutations act.
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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.