ArticleThe Journal of infectious diseases2019
Hepatitis C Virus-Escape Studies for Human Monoclonal Antibody AR4A Reveal Isolate-Specific Resistance and a High Barrier to Resistance.
Article in The Journal of infectious diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- In Vivo Determinants of Hepatitis C Virus Adaptation and Escape From Neutralizing Antibody AR5A.Cellular and molecular gastroenterology and hepatology · 2026Article
- Selection and characterization of a broadly neutralizing class of HCV anti-E2 VH1-69 antibodies.PLoS pathogens · 2025Article
- Monoclonal antibody therapeutics for infectious diseases: Beyond normal human immunoglobulin.Pharmacology & therapeutics · 2022Review
- Novel HCV Genotype 4d Infectious Systems and Assessment of Direct-Acting Antivirals and Antibody Neutralization.Viruses · 2022Article
- The Neutralizing Antibody Responses of Individuals That Spontaneously Resolve Hepatitis C Virus Infection.Viruses · 2022Article
- Mechanisms of HCV resistance to broadly neutralizing antibodies.Current opinion in virology · 2021Review
- Mechanisms of Hepatitis C Virus Escape from Vaccine-Relevant Neutralizing Antibodies.Vaccines · 2021Review
- Antibody Responses in Hepatitis C Infection.Cold Spring Harbor perspectives in medicine · 2021Review
- Antigenic and immunogenic evaluation of permutations of soluble hepatitis C virus envelope protein E2 and E1 antigens.PloS one · 2021Article
- Antibody Responses to Immunization With HCV Envelope Glycoproteins as a Baseline for B-Cell-Based Vaccine Development.Gastroenterology · 2020Article
- Hypervariable region 1 and N-linked glycans of hepatitis C regulate virion neutralization by modulating envelope conformations.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Broadly neutralizing antibodies from an individual that naturally cleared multiple hepatitis C virus infections uncover molecular determinants for E2 targeting and vaccine design.PLoS pathogens · 2019Article
- 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
- Hypervariable Region 1 in Envelope Protein 2 of Hepatitis C Virus: A Linchpin in Neutralizing Antibody Evasion and Viral Entry.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Global control of hepatitis C virus (HCV) depends on development of a prophylactic vaccine. We studied escape for cross-genotype-reactive neutralizing antibody AR4A, providing valuable information for HCV vaccine design. We cultured HCV core-NS2 recombinants H77 (genotype 1a)/JFH1 or the highly antibody-susceptible hypervariable region 1 (HVR1)-deleted variants H77/JFH1∆HVR1 and J6(genotype 2a)/JFH1∆HVR1 in Huh7.5 cells with AR4A. Long-term AR4A exposure of H77/JFH1 and H77/JFH1∆HVR1 did not yield resistance. However, J6/JFH1∆HVR1 developed the envelope-E2 substitutions I696T or I696N, which reduced AR4A binding (I696N > I696T). I696N conferred greater AR4A resistance than I696T in J6/JFH1∆HVR1, whereas the reverse was observed in J6/JFH1. This was because I696N but not I696T conferred broadly increased antibody neutralization susceptibility to J6/JFH1. I696N and I696T abrogated infectivity of H77/JFH1 and broadly increased neutralization susceptibility of S52 (genotype 3a)/JFH1. In conclusion, I696 is in the AR4A epitope, which has a high barrier to resistance, thus strengthening the rationale for its inclusion in rational HCV vaccine designs.
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