Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics
- PMID: 34852238
- DOI: 10.1016/j.cell.2021.11.009
Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics
Abstract
The human monoclonal antibody (HmAb) C10 potently cross-neutralizes Zika virus (ZIKV) and dengue virus. Analysis of antibody fragment (Fab) C10 interactions with ZIKV and dengue virus serotype 2 (DENV2) particles by cryoelectron microscopy (cryo-EM) and amide hydrogen/deuterium exchange mass spectrometry (HDXMS) shows that Fab C10 binding decreases overall ZIKV particle dynamics, whereas with DENV2, the same Fab causes increased dynamics. Testing of different Fab C10:DENV2 E protein molar ratios revealed that, at higher Fab ratios, especially at saturated concentrations, the Fab enhanced viral dynamics (detected by HDXMS), and observation under cryo-EM showed increased numbers of distorted particles. Our results suggest that Fab C10 stabilizes ZIKV but that with DENV2 particles, high Fab C10 occupancy promotes E protein dimer conformational changes leading to overall increased particle dynamics and distortion of the viral surface. This is the first instance of a broadly neutralizing antibody eliciting virus-specific increases in whole virus particle dynamics.
Keywords: DENV2; ZIKV; intradimer contacts; non-uniform epitope recognition; viral particle dynamics.
Copyright © 2021 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare no competing interests.
Comment in
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How a broadly neutralizing antibody grapples with antigenic and conformational diversity in dengue virus.Cell. 2021 Dec 9;184(25):6015-6016. doi: 10.1016/j.cell.2021.11.020. Epub 2021 Dec 1. Cell. 2021. PMID: 34856127
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