An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections.
Animals
Antibodies, Monoclonal, Humanized
/ pharmacology
Antibodies, Neutralizing
/ pharmacology
Antiviral Agents
/ pharmacology
HEK293 Cells
Hendra Virus
/ drug effects
Henipavirus Infections
/ drug therapy
Humans
Models, Molecular
Nipah Virus
/ drug effects
Viral Fusion Proteins
/ antagonists & inhibitors
Virus Internalization
/ drug effects
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
09
08
2019
accepted:
21
08
2019
pubmed:
2
10
2019
medline:
12
2
2020
entrez:
2
10
2019
Statut:
ppublish
Résumé
Nipah virus (NiV) and Hendra virus (HeV) are zoonotic henipaviruses (HNVs) responsible for outbreaks of encephalitis and respiratory illness with fatality rates of 50-100%. No vaccines or licensed therapeutics currently exist to protect humans against NiV or HeV. HNVs enter host cells by fusing the viral and cellular membranes via the concerted action of the attachment (G) and fusion (F) glycoproteins, the main targets of the humoral immune response. Here, we describe the isolation and humanization of a potent monoclonal antibody cross-neutralizing NiV and HeV. Cryo-electron microscopy, triggering and fusion studies show the antibody binds to a prefusion-specific quaternary epitope, conserved in NiV F and HeV F glycoproteins, and prevents membrane fusion and viral entry. This work supports the importance of the HNV prefusion F conformation for eliciting a robust immune response and paves the way for using this antibody for prophylaxis and post-exposure therapy with NiV- and HeV-infected individuals.
Identifiants
pubmed: 31570878
doi: 10.1038/s41594-019-0308-9
pii: 10.1038/s41594-019-0308-9
pmc: PMC6858553
mid: NIHMS1537993
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antibodies, Neutralizing
0
Antiviral Agents
0
Viral Fusion Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
980-987Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM120553
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142764
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI054715
Pays : United States
Organisme : NIH HHS
ID : S10 OD021832
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201700059C
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI077995
Pays : United States
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