Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics
| Autor: | Shuijun Zhang, T.S. Ng, Aaron W.K. Tan, Jian Shi, X.N. Lim, Xin-Xiang Lim, Ganesh S. Anand, Valerie S.Y. Chew, Shee-Mei Lok, Gavin R. Screaton, Bo Shu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Serotype
medicine.drug_class viruses Protein dimer Cross Reactions Dengue virus Antibodies Viral Monoclonal antibody medicine.disease_cause complex mixtures General Biochemistry Genetics and Molecular Biology Virus Zika virus Dengue chemistry.chemical_compound Viral Envelope Proteins medicine Humans biology Zika Virus Infection Antibodies Monoclonal Zika Virus Dengue Virus biology.organism_classification Antibodies Neutralizing Virology chemistry biology.protein lipids (amino acids peptides and proteins) Hydrogen–deuterium exchange Antibody Protein Binding |
| DOI: | 10.1016/j.cell.2021.11.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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