ArticleBMC chemical biology2009
Transcriptional profiling of the effects of 25-hydroxycholesterol on human hepatocyte metabolism and the antiviral state it conveys against the hepatitis C virus.
Article in BMC chemical biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Advances in the Prevention of Cervical Cancer by Anti-Human Papillomavirus Agents.Cancer medicine · 2025Review
- Article
- Modulation of cell proteome by 25-hydroxycholesterol and 27-hydroxycholesterol: A link between cholesterol metabolism and antiviral defense.Free radical biology & medicine · 2020Article
- The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis.Journal of Crohn's & colitis · 2019Article
- 25-Hydroxycholesterol and 27-hydroxycholesterol inhibit human rotavirus infection by sequestering viral particles into late endosomes.Redox biology · 2018Article
- Transcriptional Profiling Suggests Extensive Metabolic Rewiring of Human and Mouse Macrophages during Early Interferon Alpha Responses.Mediators of inflammation · 2018Article
- Immunometabolic Signaling Pathways Contribute to Macrophage and Dendritic Cell Function.Critical reviews in immunology · 2016Review
- Interferon Control of the Sterol Metabolic Network: Bidirectional Molecular Circuitry-Mediating Host Protection.Frontiers in immunology · 2016Review
- MicroRNAs regulate the immunometabolic response to viral infection in the liver.Nature chemical biology · 2015Article
- Interferon-stimulated genes: a complex web of host defenses.Annual review of immunology · 2014Review
- Lipids in innate antiviral defense.Cell host & microbe · 2013Review
- Sterols and oxysterols in immune cell function.Nature immunology · 2013Review
- Oxysterol-binding protein family I is the target of minor enviroxime-like compounds.Journal of virology · 2013Article
- Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol.Immunity · 2013Article
- Antiviral drugs against hepatitis C virus.Genetic vaccines and therapy · 2011Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis C virus (HCV) infection is a global health problem. A number of studies have implicated a direct role of cellular lipid metabolism in the HCV life cycle and inhibitors of the mevalonate pathway have been demonstrated to result in an antiviral state within the host cell. Transcriptome profiling was conducted on Huh-7 human hepatoma cells bearing subgenomic HCV replicons with and without treatment with 25-hydroxycholesterol (25-HC), an inhibitor of the mevalonate pathway that alters lipid metabolism, to assess metabolic determinants of pro- and antiviral states within the host cell. These data were compared with gene expression profiles from HCV-infected chimpanzees.
resultsTranscriptome profiling of Huh-7 cells treated with 25-HC gave 47 downregulated genes, 16 of which are clearly related to the mevalonate pathway. Fewer genes were observed to be upregulated (22) in the presence of 25-HC and 5 genes were uniquely upregulated in the HCV replicon bearing cells. Comparison of these gene expression profiles with data collected during the initial rise in viremia in 4 previously characterized HCV-infected chimpanzees yielded 54 overlapping genes, 4 of which showed interesting differential regulation at the mRNA level in both systems. These genes are PROX1, INSIG-1, NK4, and UBD. The expression of these genes was perturbed with siRNAs and with overexpression vectors in HCV replicon cells, and the effect on HCV replication and translation was assessed. Both PROX1 and NK4 regulated HCV replication in conjunction with an antiviral state induced by 25-hydroxycholesterol.
conclusionTreatment of Huh-7 cells bearing HCV replicons with 25-HC leads to the downregulation of many key genes involved in the mevalonate pathway leading to an antiviral state within the host cell. Furthermore, dysregulation of a larger subset of genes not directly related to the mevalonate pathway occurs both in 25-HC-treated HCV replicon harbouring cells as well as during the initial rise in viremia in infected chimpanzees. Functional studies of 3 of these genes demonstrates that they do not directly act as antiviral gene products but that they indirectly contribute to the antiviral state in the host cell. These genes may also represent novel biomarkers for HCV infection, since they demonstrate an outcome-specific expression profile.
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Registered trials
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