An antibody against the F glycoprotein inhibits Nipah and Hendra virus infections.


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
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

980-987

Subventions

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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Auteurs

Ha V Dang (HV)

Department of Biochemistry, University of Washington, Seattle, WA, USA.

Yee-Peng Chan (YP)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Young-Jun Park (YJ)

Department of Biochemistry, University of Washington, Seattle, WA, USA.

Joost Snijder (J)

Department of Biochemistry, University of Washington, Seattle, WA, USA.
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.

Sofia Cheliout Da Silva (SC)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Bang Vu (B)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Lianying Yan (L)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Yan-Ru Feng (YR)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA.

Barry Rockx (B)

Sealy Center for Vaccine Development, Departments of Pathology and Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX, USA.
Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.

Thomas W Geisbert (TW)

Sealy Center for Vaccine Development, Departments of Pathology and Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX, USA.

Chad E Mire (CE)

Sealy Center for Vaccine Development, Departments of Pathology and Microbiology & Immunology, The University of Texas Medical Branch, Galveston, TX, USA.

Christopher C Broder (CC)

Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD, USA. christopher.broder@usuhs.edu.

David Veesler (D)

Department of Biochemistry, University of Washington, Seattle, WA, USA. dveesler@uw.edu.

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