Back to Search
Start Over
A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.
- Source :
-
Cell [Cell] 2019 May 16; Vol. 177 (5), pp. 1136-1152.e18. - Publication Year :
- 2019
-
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.<br /> (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Dogs
Madin Darby Canine Kidney Cells
Mice
Antibodies, Monoclonal, Murine-Derived immunology
Antibodies, Viral immunology
Epitopes immunology
Hemagglutinin Glycoproteins, Influenza Virus immunology
Influenza A virus immunology
Influenza Vaccines immunology
Orthomyxoviridae Infections immunology
Orthomyxoviridae Infections pathology
Orthomyxoviridae Infections prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 177
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 31100268
- Full Text :
- https://doi.org/10.1016/j.cell.2019.04.011