Mechanism of differential Zika and dengue virus neutralization by a public antibody lineage targeting the DIII lateral ridge.
Aedes
Animals
Antibodies, Monoclonal
/ chemistry
Antibodies, Neutralizing
/ chemistry
Antibodies, Viral
/ chemistry
Cell Line, Tumor
Chlorocebus aethiops
Cross Reactions
Crystallography, X-Ray
Dengue
/ immunology
Dengue Virus
/ immunology
Epitopes
/ chemistry
HEK293 Cells
Humans
Hydrogen Bonding
Immunoglobulin Fab Fragments
/ chemistry
Protein Binding
/ immunology
Protein Conformation
Protein Domains
/ immunology
Vero Cells
Viral Envelope Proteins
/ chemistry
Zika Virus
/ immunology
Zika Virus Infection
/ immunology
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
03 02 2020
03 02 2020
Historique:
received:
23
09
2019
revised:
09
10
2019
accepted:
18
10
2019
pubmed:
24
11
2019
medline:
10
9
2020
entrez:
24
11
2019
Statut:
ppublish
Résumé
We previously generated a panel of human monoclonal antibodies (mAbs) against Zika virus (ZIKV) and identified one, ZIKV-116, that shares germline usage with mAbs identified in multiple donors. Here we show that ZIKV-116 interferes with ZIKV infection at a post-cellular attachment step by blocking viral fusion with host membranes. ZIKV-116 recognizes the lateral ridge of envelope protein domain III, with one critical residue varying between the Asian and African strains responsible for differential binding affinity and neutralization potency (E393D). ZIKV-116 also binds to and cross-neutralizes some dengue virus serotype 1 (DENV1) strains, with genotype-dependent inhibition explained by variation in a domain II residue (R204K) that potentially modulates exposure of the distally located, partially cryptic epitope. The V-J reverted germline configuration of ZIKV-116 preferentially binds to and neutralizes an Asian ZIKV strain, suggesting that this epitope may optimally induce related B cell clonotypes. Overall, these studies provide a structural and molecular mechanism for a cross-reactive mAb that uniquely neutralizes ZIKV and DENV1.
Identifiants
pubmed: 31757867
pii: jem.20191792
doi: 10.1084/jem.20191792
pmc: PMC7041715
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Epitopes
0
Immunoglobulin Fab Fragments
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI073755
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400018C
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI106695
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127828
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201200026C
Pays : United States
Informations de copyright
© 2019 Zhao et al.
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