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Mechanisms of HCV resistance to broadly neutralizing antibodies

Frumento, Nicole and Flyak, Andrew I. and Bailey, Justin R. (2021) Mechanisms of HCV resistance to broadly neutralizing antibodies. Current Opinion in Virology, 50 . pp. 23-29. ISSN 1879-6257. PMCID PMC8500940. doi:10.1016/j.coviro.2021.07.003. https://resolver.caltech.edu/CaltechAUTHORS:20210820-001717573

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Abstract

Broadly neutralizing antibodies (bNAbs) block infection by genetically diverse hepatitis C virus (HCV) isolates by targeting relatively conserved epitopes on the HCV envelope glycoproteins, E1 and E2. Many amino acid substitutions conferring resistance to these bNAbs have been characterized, identifying multiple mechanisms of bNAb escape. Some resistance substitutions follow the expected mechanism of directly disrupting targeted epitopes. Interestingly, other resistance substitutions fall in E2 domains distant from bNAb-targeted epitopes. These substitutions, which can confer broad resistance to multiple bNAbs, act by less clearly defined mechanisms. Some modulate binding of HCV to cell surface receptors, while others may induce conformational changes in the E2 protein. In this review, we discuss mechanisms of HCV bNAb resistance and implications for HCV vaccine development.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.coviro.2021.07.003DOIArticle
ORCID:
AuthorORCID
Frumento, Nicole0000-0002-1697-7110
Flyak, Andrew I.0000-0002-8722-479X
Additional Information:© 2021 Elsevier B.V. Available online 28 July 2021. This work was supported in part by by the National Institutes of Health grant R01 AI127469 (to JRB) and U.S. NIH grant K99 AI153465 (to AIF). Conflict of interest statement: Nothing declared.
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Funding AgencyGrant Number
NIHUNSPECIFIED
NIHUNSPECIFIED
PubMed Central ID:PMC8500940
DOI:10.1016/j.coviro.2021.07.003
Record Number:CaltechAUTHORS:20210820-001717573
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210820-001717573
Official Citation:Nicole Frumento, Andrew I Flyak, Justin R Bailey, Mechanisms of HCV resistance to broadly neutralizing antibodies, Current Opinion in Virology, Volume 50, 2021, Pages 23-29, ISSN 1879-6257, https://doi.org/10.1016/j.coviro.2021.07.003.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:110318
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:20 Aug 2021 16:05
Last Modified:02 Nov 2021 22:35

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