Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics.
Cell
; 184(25): 6067-6080.e13, 2021 12 09.
Article
en En
| MEDLINE
| ID: mdl-34852238
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 C10DENV2 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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas del Envoltorio Viral
/
Dengue
/
Virus del Dengue
/
Anticuerpos Neutralizantes
/
Virus Zika
/
Infección por el Virus Zika
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2021
Tipo del documento:
Article
País de afiliación:
Singapur