Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.cell.2021.11.009
Title: Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics
Authors: LIM XIN XIANG
SHU BO 
ZHANG SHUIJUN
AARON TAN WAI KIT 
Ng Thiam Seng 
Lim Xin Ni
CHEW SHYN YUN VALERIE
Shi Jian 
Gavin R. Screaton
Lok Shee Mei
Ganesh Srinivasan Anand
Keywords: DENV2; ZIKV; intradimer contacts; non-uniform epitope recognition; viral particle dynamics.
Issue Date: 9-Dec-2021
Citation: LIM XIN XIANG, SHU BO, ZHANG SHUIJUN, AARON TAN WAI KIT, Ng Thiam Seng, Lim Xin Ni, CHEW SHYN YUN VALERIE, Shi Jian, Gavin R. Screaton, Lok Shee Mei, Ganesh Srinivasan Anand (2021-12-09). Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics. ScholarBank@NUS Repository. https://doi.org/10.1016/j.cell.2021.11.009
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.
URI: https://scholarbank.nus.edu.sg/handle/10635/217856
DOI: 10.1016/j.cell.2021.11.009
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
Lim_and_Zhang_etal_Text.pdf523.18 kBAdobe PDF

OPEN

Pre-printView/Download
Lim_and_Zhang_etal_Figures.pdf7.11 MBAdobe PDF

OPEN

Pre-printView/Download

SCOPUSTM   
Citations

4
checked on Oct 1, 2022

Page view(s)

86
checked on Oct 6, 2022

Download(s)

14
checked on Oct 6, 2022

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.