ArticlePloS one2014
Up-regulation of the ATP-binding cassette transporter A1 inhibits hepatitis C virus infection.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 56 citations in OpenAlex.
- Role of liver X receptors in the pathogenesis and treatment of chronic liver disease (Review).Molecular medicine reports · 2026Review
- Cholesterol-dependent control of endosomal escape regulates intracellular trafficking of small interfering RNA therapeutics and interactions with small molecule drugs.The Journal of pharmacology and experimental therapeutics · 2026Article
- Identification of an uncharacterized protein as a novel regulator ofJournal of virology · 2025Article
- Liver X Receptor-Inducible Host E3 Ligase IDOL Targets a Human Cytomegalovirus Reactivation Determinant.Journal of virology · 2023Article
- Article
- Lipid Raft Integrity and Cellular Cholesterol Homeostasis Are Critical for SARS-CoV-2 Entry into Cells.Nutrients · 2022Article
- Pseudorabies Virus Inhibits Expression of Liver X Receptors to Assist Viral Infection.Viruses · 2022Article
- Abundance of Nef and p-Tau217 in Brains of Individuals Diagnosed with HIV-Associated Neurocognitive Disorders Correlate with Disease Severance.Molecular neurobiology · 2022Article
- Trophoblast Differentiation Affects Crucial Nutritive Functions of Placental Membrane Transporters.Frontiers in cell and developmental biology · 2022Article
- Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids.Membranes · 2021Review
- Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.PLoS pathogens · 2021Article
- Fatty Acid Synthase Is Involved in Classical Swine Fever Virus Replication by Interaction with NS4B.Journal of virology · 2021Article
- Global analysis of HBV-mediated host proteome and ubiquitylome change in HepG2.2.15 human hepatoblastoma cell line.Cell & bioscience · 2021Article
- The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease.International journal of molecular sciences · 2021Review
- The ins and outs of lipid rafts: functions in intracellular cholesterol homeostasis, microparticles, and cell membranes: Thematic Review Series: Biology of Lipid Rafts.Journal of lipid research · 2020Review
- Differential expression of microRNA, miR-150 and enhancer of zeste homolog 2 (EZH2) in peripheral blood cells as early prognostic markers of severe forms of dengue.Journal of biomedical science · 2020Article
- Analysis of Low Molecular Weight Substances and Related Processes Influencing Cellular Cholesterol Efflux.Pharmaceutical medicine · 2019Review
- LXR Alpha Restricts Gammaherpesvirus Reactivation from Latently Infected Peritoneal Cells.Journal of virology · 2019Article
- Genome-wide association study (GWAS) of human host factors influencing viral severity of herpes simplex virus type 2 (HSV-2).Genes and immunity · 2019Article
- Article
Corrections and comments
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Authors and funding
17 authors at 12 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis C virus (HCV) establishes infection using host lipid metabolism pathways that are thus considered potential targets for indirect anti-HCV strategies. HCV enters the cell via clathrin-dependent endocytosis, interacting with several receptors, and virus-cell fusion, which depends on acidic pH and the integrity of cholesterol-rich domains of the hepatocyte membrane. The ATP-binding Cassette Transporter A1 (ABCA1) mediates cholesterol efflux from hepatocytes to extracellular Apolipoprotein A1 and moves cholesterol within cell membranes. Furthermore, it generates high-density lipoprotein (HDL) particles. HDL protects against arteriosclerosis and cardiovascular disease. We show that the up-regulation of ABCA1 gene expression and its cholesterol efflux function in Huh7.5 hepatoma cells, using the liver X receptor (LXR) agonist GW3965, impairs HCV infection and decreases levels of virus produced. ABCA1-stimulation inhibited HCV cell entry, acting on virus-host cell fusion, but had no impact on virus attachment, replication, or assembly/secretion. It did not affect infectivity or properties of virus particles produced. Silencing of the ABCA1 gene and reduction of the specific cholesterol efflux function counteracted the inhibitory effect of the GW3965 on HCV infection, providing evidence for a key role of ABCA1 in this process. Impaired virus-cell entry correlated with the reorganisation of cholesterol-rich membrane microdomains (lipid rafts). The inhibitory effect could be reversed by an exogenous cholesterol supply, indicating that restriction of HCV infection was induced by changes of cholesterol content/distribution in membrane regions essential for virus-cell fusion. Stimulation of ABCA1 expression by GW3965 inhibited HCV infection of both human primary hepatocytes and isolated human liver slices. This study reveals that pharmacological stimulation of the ABCA1-dependent cholesterol efflux pathway disrupts membrane cholesterol homeostasis, leading to the inhibition of virus-cell fusion and thus HCV cell entry. Therefore besides other beneficial roles, ABCA1 might represent a potential target for HCV therapy.
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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.