ArticleThe Journal of biological chemistry2015
Structural basis for penetration of the glycan shield of hepatitis C virus E2 glycoprotein by a broadly neutralizing human antibody.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 77 citations in OpenAlex.
- A potently neutralizing and protective human antibody targeting antigenic site V on RSV and hMPV fusion glycoprotein.Cell reports. Medicine · 2026Article
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- GLYCO-BUILD: an enzymatic pipeline for the synthesis of peptides carrying eukaryotic N-glycans.Nature communications · 2025Article
- Cryo-EM structures of HCV E2 glycoprotein bound to neutralizing and non-neutralizing antibodies determined using bivalent Fabs as fiducial markers.Communications biology · 2025Article
- Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.Science advances · 2024Article
- A potently neutralizing and protective human antibody targeting antigenic site V on RSV and hMPV fusion glycoprotein.bioRxiv : the preprint server for biology · 2024Article
- Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development.Viruses · 2024Review
- Prospects for developing an Hepatitis C virus E1E2-based nanoparticle vaccine.Reviews in medical virology · 2023Review
- Structure of engineered hepatitis C virus E1E2 ectodomain in complex with neutralizing antibodies.Nature communications · 2023Article
- Current Hepatitis C Vaccine Candidates Based on the Induction of Neutralizing Antibodies.Viruses · 2023Review
- The Neutralizing Antibody Responses of Individuals That Spontaneously Resolve Hepatitis C Virus Infection.Viruses · 2022Article
- Structural Features of Antibody-Peptide Recognition.Frontiers in immunology · 2022Article
- Mechanisms of HCV resistance to broadly neutralizing antibodies.Current opinion in virology · 2021Review
- Structural perspectives on HCV humoral immune evasion mechanisms.Current opinion in virology · 2021Review
- Hepatitis C Virus Glycan-Dependent Interactions and the Potential for Novel Preventative Strategies.Pathogens (Basel, Switzerland) · 2021Review
- Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development.Viruses · 2021Review
- Review
- From Structural Studies to HCV Vaccine Design.Viruses · 2021Review
- Review
- Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies.Vaccines · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. A challenge for HCV vaccine development is to identify conserved epitopes able to elicit protective antibodies against this highly diverse virus. Glycan shielding is a mechanism by which HCV masks such epitopes on its E2 envelope glycoprotein. Antibodies to the E2 region comprising residues 412-423 (E2(412-423)) have broadly neutralizing activities. However, an adaptive mutation in this linear epitope, N417S, is associated with a glycosylation shift from Asn-417 to Asn-415 that enables HCV to escape neutralization by mAbs such as HCV1 and AP33. By contrast, the human mAb HC33.1 can neutralize virus bearing the N417S mutation. To understand how HC33.1 penetrates the glycan shield created by the glycosylation shift to Asn-415, we determined the structure of this broadly neutralizing mAb in complex with its E2(412-423) epitope to 2.0 Å resolution. The conformation of E2(412-423) bound to HC33.1 is distinct from the β-hairpin conformation of this peptide bound to HCV1 or AP33, because of disruption of the β-hairpin through interactions with the unusually long complementarity-determining region 3 of the HC33.1 heavy chain. Whereas Asn-415 is buried by HCV1 and AP33, it is solvent-exposed in the HC33.1-E2(412-423) complex, such that glycosylation of Asn-415 would not prevent antibody binding. Furthermore, our results highlight the structural flexibility of the E2(412-423) epitope, which may serve as an immune evasion strategy to impede induction of antibodies targeting this site by reducing its antigenicity.
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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.