ArticleProceedings of the National Academy of Sciences of the United States of America2016
Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 90 citations in OpenAlex.
- Structural and biochemical insights into HCV envelope proteins for germline-targeting vaccines.PLoS pathogens · 2026Article
- Structure-based design of stable recombinant hepatitis C virus E1E2 heterodimers.Nature communications · 2026Article
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- Antigenic and EM characterization of the Chiron experimental hepatitis C virus vaccine.Vaccine · 2025Article
- Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.Science advances · 2024Article
- Article
- Sustained Long-Term Decline in Anti-HCV Neutralizing Antibodies in HIV/HCV-Coinfected Patients Five Years after HCV Therapy: A Retrospective Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Hepatitis C Virus E1E2 Structure, Diversity, and Implications for Vaccine Development.Viruses · 2024Review
- Glycan heterogeneity as a cause of the persistent fraction in HIV-1 neutralization.PLoS pathogens · 2023Article
- Prospects for developing an Hepatitis C virus E1E2-based nanoparticle vaccine.Reviews in medical virology · 2023Review
- Signatures of VNature communications · 2023Article
- 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
- Three-Dimensional Reconstruction of the Hepatitis C Virus Envelope Glycoprotein E1E2 Heterodimer by Electron Microscopic Analysis.Journal of virology · 2023Article
- HCV E1 influences the fitness landscape of E2 and may enhance escape from E2-specific antibodies.Virus evolution · 2023Article
- Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate.Nature communications · 2022Article
- Bioprocess development for biosurfactant production by Natrialba sp. M6 with effective direct virucidal and anti-replicative potential against HCV and HSV.Scientific reports · 2022Article
- Article
- Conformational plasticity of the HIV-1 gp41 immunodominant region is recognized by multiple non-neutralizing antibodies.Communications biology · 2022Article
- Evolutionary modeling reveals enhanced mutational flexibility of HCV subtype 1b compared with 1a.iScience · 2022Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatitis C virus (HCV) is a major cause of liver disease, affecting over 2% of the world's population. The HCV envelope glycoproteins E1 and E2 mediate viral entry, with E2 being the main target of neutralizing antibody responses. Structural investigations of E2 have produced templates for vaccine design, including the conserved CD81 receptor-binding site (CD81bs) that is a key target of broadly neutralizing antibodies (bNAbs). Unfortunately, immunization with recombinant E2 and E1E2 rarely elicits sufficient levels of bNAbs for protection. To understand the challenges for eliciting bNAb responses against the CD81bs, we investigated the E2 CD81bs by electron microscopy (EM), hydrogen-deuterium exchange (HDX), molecular dynamics (MD), and calorimetry. By EM, we observed that HCV1, a bNAb recognizing the N-terminal region of the CD81bs, bound a soluble E2 core construct from multiple angles of approach, suggesting components of the CD81bs are flexible. HDX of multiple E2 constructs consistently indicated the entire CD81bs was flexible relative to the rest of the E2 protein, which was further confirmed by MD simulations. However, E2 has a high melting temperature of 84.8 °C, which is more akin to proteins from thermophilic organisms. Thus, recombinant E2 is a highly stable protein overall, but with an exceptionally flexible CD81bs. Such flexibility may promote induction of nonneutralizing antibodies over bNAbs to E2 CD81bs, underscoring the necessity of rigidifying this antigenic region as a target for rational vaccine design.
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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.