ArticleThe Journal of biological chemistry2011
Hepatitis C virus is primed by CD81 protein for low pH-dependent fusion.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 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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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
65 citing papers in PubMed, 112 citations in OpenAlex.
- A Double-Edged Sword: Extracellular Serine Proteases as Facilitators of Infection and Mediators of Immunity.Molecules (Basel, Switzerland) · 2026Review
- Review
- Pathogenesis, prevention, and therapeutic advances in hepatitis B, C, and D.Virology journal · 2025Review
- Article
- A comprehensive overview on the crosstalk between microRNAs and viral pathogenesis and infection.Medicinal research reviews · 2025Review
- Hepatitis B virus entry, assembly, and egress.Microbiology and molecular biology reviews : MMBR · 2024Review
- Antiviral Protein-Protein Interaction Inhibitors.Journal of medicinal chemistry · 2024Review
- Hepatitis C virus E1 recruits high-density lipoprotein to support infectivity and evade antibody recognition.Journal of virology · 2024Article
- Structures of the Hepaci-, Pegi-, and Pestiviruses envelope proteins suggest a novel membrane fusion mechanism.PLoS biology · 2023Article
- Regions of hepatitis C virus E2 required for membrane association.Nature communications · 2023Article
- Article
- Bone marrow mesenchymal stem cell-derived exosomal miR-34c-5p ameliorates RIF by inhibiting the core fucosylation of multiple proteins.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Cellular factors involved in the hepatitis C virus life cycle.World journal of gastroenterology · 2021Review
- Fluoxazolevir inhibits hepatitis C virus infection in humanized chimeric mice by blocking viral membrane fusion.Nature microbiology · 2020Article
- Single-nucleotide variants in human CD81 influence hepatitis C virus infection of hepatoma cells.Medical microbiology and immunology · 2020Article
- 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
- Article
- Regulation of cytoskeleton and adhesion signaling in osteoclasts by tetraspanin CD82.Bone reports · 2019Article
- Functional expression and characterization of the envelope glycoprotein E1E2 heterodimer of hepatitis C virus.PLoS pathogens · 2019Article
5 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
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Hepatitis C virus (HCV) entry into permissive cells is a complex process that involves interactions with at least four co-factors followed by endocytosis and low pH-dependent fusion with endosomes. The precise sequence of receptor engagement and their roles in promoting HCV E1E2 glycoprotein-mediated fusion are poorly characterized. Because cell-free HCV tolerates an acidic environment, we hypothesized that binding to one or more receptors on the cell surface renders E1E2 competent to undergo low pH-induced conformational changes and promote fusion with endosomes. To test this hypothesis, we examined the effects of low pH and of the second extracellular loop (ECL2) of CD81, one of the four entry factors, on HCV infectivity. Pretreatment with an acidic buffer or with ECL2 enhanced infection through changing the E1E2 conformation, as evidenced by the altered reactivity of these proteins with conformation-specific antibodies and stable association with liposomes. However, neither of the two treatments alone permitted direct fusion with the cell plasma membrane. Sequential HCV preincubation with ECL2 and acidic buffer in the absence of target cells resulted in a marked loss of infectivity, implying that the receptor-bound HCV is primed for low pH-dependent conformational changes. Indeed, soluble receptor-pretreated HCV fused with the cell plasma membrane at low pH under conditions blocking an endocytic entry pathway. These findings suggest that CD81 primes HCV for low pH-dependent fusion early in the entry process. The simple triggering paradigm and intermediate conformations of E1E2 identified in this study could help guide future vaccine and therapeutic efforts to block HCV infection.
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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.