Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics

Xin Xiang Lim; Bo Shu; Shuijun Zhang; Aaron W.K. Tan; Thiam Seng Ng; Xin Ni Lim; Valerie S.Y. Chew; Jian Shi; Gavin R. Screaton; Shee Mei Lok; Ganesh S. Anand

doi:10.1016/j.cell.2021.11.009

Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics

Xin Xiang Lim
, Bo Shu
, Shuijun Zhang
, Aaron W.K. Tan
, Thiam Seng Ng
, Xin Ni Lim
, Valerie S.Y. Chew
, Jian Shi
, Gavin R. Screaton
, Shee Mei Lok
, Ganesh S. Anand

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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.

Original language	English (US)
Pages (from-to)	6067-6080.e13
Journal	Cell
Volume	184
Issue number	25
DOIs	https://doi.org/10.1016/j.cell.2021.11.009
State	Published - Dec 9 2021

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2021.11.009

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@article{ed9b666e081043c09779c53d7357e282,

title = "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.",

author = "Lim, \{Xin Xiang\} and Bo Shu and Shuijun Zhang and Tan, \{Aaron W.K.\} and Ng, \{Thiam Seng\} and Lim, \{Xin Ni\} and Chew, \{Valerie S.Y.\} and Jian Shi and Screaton, \{Gavin R.\} and Lok, \{Shee Mei\} and Anand, \{Ganesh S.\}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = dec,

day = "9",

doi = "10.1016/j.cell.2021.11.009",

language = "English (US)",

volume = "184",

pages = "6067--6080.e13",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

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TY - JOUR

T1 - Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics

AU - Lim, Xin Xiang

AU - Shu, Bo

AU - Zhang, Shuijun

AU - Tan, Aaron W.K.

AU - Ng, Thiam Seng

AU - Lim, Xin Ni

AU - Chew, Valerie S.Y.

AU - Shi, Jian

AU - Screaton, Gavin R.

AU - Lok, Shee Mei

AU - Anand, Ganesh S.

PY - 2021/12/9

Y1 - 2021/12/9

N2 - 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.

AB - 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.

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UR - https://www.scopus.com/pages/publications/85120622903#tab=citedBy

U2 - 10.1016/j.cell.2021.11.009

DO - 10.1016/j.cell.2021.11.009

M3 - Article

C2 - 34852238

AN - SCOPUS:85120622903

SN - 0092-8674

VL - 184

SP - 6067-6080.e13

JO - Cell

JF - Cell

IS - 25

ER -

Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics

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