ArticlePloS one2013
Apolipoprotein E mediates attachment of clinical hepatitis C virus to hepatocytes by binding to cell surface heparan sulfate proteoglycan receptors.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Novel combined single dose anti-hepatitis C therapy: a pilot study.Scientific reports · 2021Trial
- Addition of Epigallocatechin Gallate 400 mg to Sofosbuvir 400 mg + Daclatisvir 60 mg With or Without Ribavirin in Treatment of Patients with Chronic Hepatitis C Improves the Safety Profile: A Pilot Study.Scientific reports · 2019Trial
- Promotion of hepatitis B virus infection by extracellular apolipoprotein E.Journal of virology · 2026Article
- Apolipoprotein E selectively supports gammaherpesvirus replication in macrophages.Journal of virology · 2025Article
- Recruitment of apolipoprotein E facilitates Herpes simplex virus 1 attachment and release.Npj viruses · 2025Article
- CRISPR/Cas9 as a New Antiviral Strategy for Treating Hepatitis Viral Infections.International journal of molecular sciences · 2023Review
- Apolipoprotein E and viral infection: Risks and Mechanisms.Molecular therapy. Nucleic acids · 2023Review
- Apolipoprotein E, a Crucial Cellular Protein in the Lifecycle of Hepatitis Viruses.International journal of molecular sciences · 2022Review
- What role for cellular metabolism in the control of hepatitis viruses?Frontiers in immunology · 2022Review
- Cellular factors involved in the hepatitis C virus life cycle.World journal of gastroenterology · 2021Review
- Human low-density lipoprotein receptor plays an important role in hepatitis B virus infection.PLoS pathogens · 2021Article
- Hepatitis C Virus Uses Host Lipids to Its Own Advantage.Metabolites · 2021Review
- Interactions of SARS-CoV-2 with the Blood-Brain Barrier.International journal of molecular sciences · 2021Review
- The ApoE Locus and COVID-19: Are We Going Where We Have Been?The journals of gerontology. Series A, Biological sciences and medical sciences · 2021Article
- Hepatitis C Virus Entry: An Intriguingly Complex and Highly Regulated Process.International journal of molecular sciences · 2020Review
- Hepatitis C Virus Entry: Protein Interactions and Fusion Determinants Governing Productive Hepatocyte Invasion.Cold Spring Harbor perspectives in medicine · 2020Review
- Human apolipoprotein E promotes hepatitis B virus infection and production.PLoS pathogens · 2019Article
- The Role of ApoE in HCV Infection and Comorbidity.International journal of molecular sciences · 2019Review
- The neutralization of heparan sulfate by heparin-binding copolymer as a potential therapeutic target.RSC advances · 2019Article
- Attachment and Postattachment Receptors Important for Hepatitis C Virus Infection and Cell-to-Cell Transmission.Journal of virology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Our previous studies demonstrated that the cell culture-grown hepatitis C virus of genotype 2a (HCVcc) uses apolipoprotein E (apoE) to mediate its attachment to the surface of human hepatoma Huh-7.5 cells. ApoE mediates HCV attachment by binding to the cell surface heparan sulfate (HS) which is covalently attached to the core proteins of proteoglycans (HSPGs). In the present study, we further determined the physiological importance of apoE and HSPGs in the HCV attachment using a clinical HCV of genotype 1b (HCV1b) obtained from hepatitis C patients and human embryonic stem cell-differentiated hepatocyte-like cells (DHHs). DHHs were found to resemble primary human hepatocytes. Similar to HCVcc, HCV1b was found to attach to the surface of DHHs by the apoE-mediated binding to the cell surface HSPGs. The apoE-specific monoclonal antibody, purified HSPGs, and heparin were all able to efficiently block HCV1b attachment to DHHs. Similarly, the removal of heparan sulfate from cell surface by treatment with heparinase suppressed HCV1b attachment to DHHs. More significantly, HCV1b attachment was potently inhibited by a synthetic peptide derived from the apoE receptor-binding region as well as by an HSPG-binding peptide. Likewise, the HSPG-binding peptide prevented apoE from binding to heparin in a dose-dependent manner, as determined by an in vitro heparin pull-down assay. Collectively, these findings demonstrate that HSPGs serve as major HCV attachment receptors on the surface of human hepatocytes to which the apoE protein ligand on the HCV envelope binds.
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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.