A Human Antibody Neutralizes Different Flaviviruses by Using Different Mechanisms.
cryoEM structure
dengue virus
human antibody
membrane fusion
virus aggregation
virus neutralization
zika virus
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
28 04 2020
28 04 2020
Historique:
received:
07
10
2019
revised:
25
02
2020
accepted:
07
04
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
14
5
2021
Statut:
ppublish
Résumé
Human antibody SIgN-3C neutralizes dengue virus (DENV) and Zika virus (ZIKV) differently. DENV:SIgN-3C Fab and ZIKV:SIgN-3C Fab cryoelectron microscopy (cryo-EM) complex structures show Fabs crosslink E protein dimers at extracellular pH 8.0 condition and also when further incubated at acidic endosomal conditions (pH 8.0-6.5). We observe Fab binding to DENV (pH 8.0-5.0) prevents virus fusion, and the number of bound Fabs increase (from 120 to 180). For ZIKV, although there are already 180 copies of Fab at pH 8.0, virus structural changes at pH 5.0 are not inhibited. The immunoglobulin G (IgG):DENV structure at pH 8.0 shows both Fab arms bind to epitopes around the 2-fold vertex. On ZIKV, an additional Fab around the 5-fold vertex at pH 8.0 suggests one IgG arm would engage with an epitope, although the other may bind to other viruses, causing aggregation. For DENV2 at pH 5.0, a similar scenario would occur, suggesting DENV2:IgG complex would aggregate in the endosome. Hence, a single antibody employs different neutralization mechanisms against different flaviviruses.
Identifiants
pubmed: 32348755
pii: S2211-1247(20)30533-7
doi: 10.1016/j.celrep.2020.107584
pii:
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107584Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.