A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.

Animals Antibodies, Monoclonal, Murine-Derived / immunology Antibodies, Viral / immunology Dogs Epitopes / immunology Hemagglutinin Glycoproteins, Influenza Virus / immunology Influenza A virus / immunology Influenza Vaccines / immunology Madin Darby Canine Kidney Cells Mice Orthomyxoviridae Infections / immunology
B-lymphocytes antibodies antibody-dependent cell cytotoxicity antigen-antibody reactions hemagglutinin glycoproteins influenza A virus influenza virus monoclonal viral

Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
16 05 2019
Historique:
received: 23 07 2018
revised: 25 02 2019
accepted: 04 04 2019
entrez: 18 5 2019
pubmed: 18 5 2019
medline: 12 2 2020
Statut: ppublish

Résumé

Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.

Identifiants

DOI: 10.1016/j.cell.2019.04.011 PMID: 31100268 PMC: PMC6629437
pubmed: 31100268
pii: S0092-8674(19)30397-6
doi: 10.1016/j.cell.2019.04.011
pmc: PMC6629437
mid: NIHMS1528122
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Murine-Derived 0
Antibodies, Viral 0
Epitopes 0
Hemagglutinin Glycoproteins, Influenza Virus 0
Influenza Vaccines 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1136-1152.e18

Subventions

Organisme : NIAID NIH HHS
ID : HHSN272201400024C
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM094586
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI127371
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI117905
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI097092
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002243
Pays : United States
Organisme : NIGMS NIH HHS
ID : P41 GM103393
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

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Auteurs

Sandhya Bangaru (S)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Shanshan Lang (S)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Michael Schotsaert (M)

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Hillary A Vanderven (HA)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.

Xueyong Zhu (X)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Nurgun Kose (N)

The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Robin Bombardi (R)

The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Jessica A Finn (JA)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Stephen J Kent (SJ)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.

Pavlo Gilchuk (P)

The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Iuliia Gilchuk (I)

The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.

Hannah L Turner (HL)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Adolfo García-Sastre (A)

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Sheng Li (S)

Department of Medicine and Biomedical Sciences, School of Medicine, University of California, San Diego, CA 92093, USA.

Andrew B Ward (AB)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Ian A Wilson (IA)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wilson@scripps.edu.

James E Crowe (JE)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: james.crowe@vanderbilt.edu.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux d'origine murine › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Carnivora › Pinnipedia › Canidae › Chiens › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Épitopes › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines virales › Protéines virales structurales › Protéines de l'enveloppe virale › Glycoprotéine hémagglutinine du virus influenza › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Orthomyxoviridae › Influenzavirus A › Virus de la grippe A › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Mélanges complexes › Produits biologiques › Vaccins › Vaccins antiviraux › Vaccins antigrippaux › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules rénales canines Madin-Darby › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › A Site of Vulnerability on the Influenza Virus...
questionsmedicales.fr › Infection › Maladies virales › Infections à virus à ARN › Infections à Orthomyxoviridae › A Site of Vulnerability on the Influenza Virus...