ArticleJournal of virology2018
Escape of Hepatitis C Virus from Epitope I Neutralization Increases Sensitivity of Other Neutralization Epitopes.
Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- Antibody responses to a highly conserved peptide in HCV E2 protein correlate with chronicity or spontaneous clearance of HCV infection.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- In Vivo Determinants of Hepatitis C Virus Adaptation and Escape From Neutralizing Antibody AR5A.Cellular and molecular gastroenterology and hepatology · 2026Article
- Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.Science advances · 2024Article
- Current Hepatitis C Vaccine Candidates Based on the Induction of Neutralizing Antibodies.Viruses · 2023Review
- Virus-Like Particles Containing the E2 Core Domain of Hepatitis C Virus Generate Broadly Neutralizing Antibodies in Guinea Pigs.Journal of virology · 2022Article
- Mechanisms of HCV resistance to broadly neutralizing antibodies.Current opinion in virology · 2021Review
- Structural and Biophysical Characterization of the HCV E1E2 Heterodimer for Vaccine Development.Viruses · 2021Review
- From Structural Studies to HCV Vaccine Design.Viruses · 2021Review
- Review
- Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies.Vaccines · 2021Review
- Development of a structural epitope mimic: an idiotypic approach to HCV vaccine design.NPJ vaccines · 2021Article
- HCV Glycoprotein Structure and Implications for B-Cell Vaccine Development.International journal of molecular sciences · 2020Review
- Global and local envelope protein dynamics of hepatitis C virus determine broad antibody sensitivity.Science advances · 2020Article
- Enhancing the antigenicity and immunogenicity of monomeric forms of hepatitis C virus E2 for use as a preventive vaccine.The Journal of biological chemistry · 2020Article
- Hepatitis C Virus Vaccine: Challenges and Prospects.Vaccines · 2020Review
- Hepatitis C Virus Escape Studies of Human Antibody AR3A Reveal a High Barrier to Resistance and Novel Insights on Viral Antibody Evasion Mechanisms.Journal of virology · 2019Article
- The Neutralizing Face of Hepatitis C Virus E2 Envelope Glycoprotein.Frontiers in immunology · 2018Review
- Conformational Flexibility in the CD81-Binding Site of the Hepatitis C Virus Glycoprotein E2.Frontiers in immunology · 2018Review
- Computational Modeling of Hepatitis C Virus Envelope Glycoprotein Structure and Recognition.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis C virus (HCV) E2 glycoprotein is a major target of the neutralizing antibody (nAb) response, with multiple type-specific and broadly neutralizing antibody (bnAb) epitopes identified. The 412-to-423 region can generate bnAbs that block interaction with the cell surface receptor CD81, with activity toward multiple HCV genotypes. In this study, we reveal the structure of rodent monoclonal antibody 24 (MAb24) with an extensive contact area toward a peptide spanning the 412-to-423 region. The crystal structure of the MAb24-peptide 412-to-423 complex reveals the paratope bound to a peptide hairpin highly similar to that observed with human MAb HCV1 and rodent MAb AP33, but with a different angle of approach. In viral outgrowth experiments, we demonstrated three distinct genotype 2a viral populations that acquired resistance to MAb24 via N415D, N417S, and N415D/H386R mutations. Importantly, the MAb24-resistant viruses exhibited significant increases in sensitivity to the majority of bnAbs directed to epitopes within the 412-to-423 region and in additional antigenic determinants located within E2 and the E1E2 complex. This study suggests that modification of N415 causes a global change in glycoprotein structure that increases its vulnerability to neutralization by other antibodies. This finding suggests that in the context of an antibody response to viral infection, acquisition of escape mutations in the 412-to-423 region renders the virus more susceptible to neutralization by other specificities of nAbs, effectively reducing the immunological fitness of the virus. A vaccine for HCV that generates polyspecific humoral immunity with specificity for the 412-to-423 region and at least one other region of E2 is desirable.
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