A 2.8-Angstrom-Resolution Cryo-Electron Microscopy Structure of Human Parechovirus 3 in Complex with Fab from a Neutralizing Antibody.
Antibodies, Monoclonal
/ immunology
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Capsid
/ metabolism
Capsid Proteins
/ immunology
Cell Line, Tumor
Cryoelectron Microscopy
/ methods
Epitopes
/ metabolism
Humans
Immunoglobulin Fab Fragments
/ immunology
Parechovirus
/ immunology
cryo-EM
genome packaging
human parechovirus 3
neutralizing antibodies
picornavirus
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 02 2019
15 02 2019
Historique:
received:
11
09
2018
accepted:
09
11
2018
pubmed:
23
11
2018
medline:
7
1
2020
entrez:
23
11
2018
Statut:
epublish
Résumé
Human parechovirus 3 (HPeV3) infection is associated with sepsis characterized by significant immune activation and subsequent tissue damage in neonates. Strategies to limit infection have been unsuccessful due to inadequate molecular diagnostic tools for early detection and the lack of a vaccine or specific antiviral therapy. Toward the latter, we present a 2.8-Å-resolution structure of HPeV3 in complex with fragments from a neutralizing human monoclonal antibody, AT12-015, using cryo-electron microscopy (cryo-EM) and image reconstruction. Modeling revealed that the epitope extends across neighboring asymmetric units with contributions from capsid proteins VP0, VP1, and VP3. Antibody decoration was found to block binding of HPeV3 to cultured cells. Additionally, at high resolution, it was possible to model a stretch of RNA inside the virion and, from this, identify the key features that drive and stabilize protein-RNA association during assembly.
Identifiants
pubmed: 30463974
pii: JVI.01597-18
doi: 10.1128/JVI.01597-18
pmc: PMC6364030
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Capsid Proteins
0
Epitopes
0
Immunoglobulin Fab Fragments
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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