Unknown

Dataset Information

0

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


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.

SUBMITTER: Bangaru S 

PROVIDER: S-EPMC6629437 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 i  ...[more]

Similar Datasets

| S-EPMC7456233 | biostudies-literature
| S-EPMC8321569 | biostudies-literature
| S-EPMC8310015 | biostudies-literature
| S-EPMC6041311 | biostudies-literature
| S-EPMC8262862 | biostudies-literature
2018-06-05 | GSE113831 | GEO
| S-EPMC7704708 | biostudies-literature
| S-EPMC4473583 | biostudies-literature
2024-04-29 | GSE252606 | GEO
| S-EPMC6069205 | biostudies-literature