A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.
Cell
; 177(5): 1136-1152.e18, 2019 05 16.
Article
em En
| MEDLINE
| ID: mdl-31100268
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
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Vacinas contra Influenza
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Infecções por Orthomyxoviridae
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Glicoproteínas de Hemaglutininação de Vírus da Influenza
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Anticorpos Monoclonais Murinos
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Anticorpos Antivirais
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Epitopos
Limite:
Animals
Idioma:
En
Revista:
Cell
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos