Mechanisms of HCV resistance to broadly neutralizing antibodies
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.
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.Attached Files
Accepted Version - nihms-1728485.pdf
Files
Name | Size | Download all |
---|---|---|
md5:fdad8c533ce2be6228f59dc1cad231f9
|
517.3 kB | Preview Download |
Additional details
- PMCID
- PMC8500940
- Eprint ID
- 110318
- Resolver ID
- CaltechAUTHORS:20210820-001717573
- NIH
- NIH
- Created
-
2021-08-20Created from EPrint's datestamp field
- Updated
-
2023-07-07Created from EPrint's last_modified field