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

Journal article

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.

Authors: Lim, X-X; Shu, B; Zhang, S; Tan, AWK; Ng, T-S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Cell Press
• Journal: Cell
• Volume: 184
• Issue: 25
• Article number: 6067-6080.E13
• Publication date: 2021-11-30
• Acceptance date: 2021-11-08
• DOI: 10.1016/j.cell.2021.11.009
• EISSN: 1097-4172
• ISSN: 0092-8674
• Pmid: 34852238
• Language: English
• Keywords: non-uniform epitope recognition; ZIKV; intradimer contacts; DENV2; viral particle dynamics; FFR