tetano
Editor, Senior Moderator
Cell. 2019 May 16;177(5):1136-1152.e18. doi: 10.1016/j.cell.2019.04.011.
[h=1]A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.[/h] Bangaru S[SUP]1[/SUP], Lang S[SUP]2[/SUP], Schotsaert M[SUP]3[/SUP], Vanderven HA[SUP]4[/SUP], Zhu X[SUP]2[/SUP], Kose N[SUP]5[/SUP], Bombardi R[SUP]5[/SUP], Finn JA[SUP]1[/SUP], Kent SJ[SUP]4[/SUP], Gilchuk P[SUP]5[/SUP], Gilchuk I[SUP]5[/SUP], Turner HL[SUP]2[/SUP], Garc?a-Sastre A[SUP]6[/SUP], Li S[SUP]7[/SUP], Ward AB[SUP]2[/SUP], Wilson IA[SUP]8[/SUP], Crowe JE Jr[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] B-lymphocytes; antibodies; antibody-dependent cell cytotoxicity; antigen-antibody reactions; hemagglutinin glycoproteins; influenza A virus; influenza virus; monoclonal; viral
PMID: 31100268 DOI: 10.1016/j.cell.2019.04.011
[h=1]A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.[/h] Bangaru S[SUP]1[/SUP], Lang S[SUP]2[/SUP], Schotsaert M[SUP]3[/SUP], Vanderven HA[SUP]4[/SUP], Zhu X[SUP]2[/SUP], Kose N[SUP]5[/SUP], Bombardi R[SUP]5[/SUP], Finn JA[SUP]1[/SUP], Kent SJ[SUP]4[/SUP], Gilchuk P[SUP]5[/SUP], Gilchuk I[SUP]5[/SUP], Turner HL[SUP]2[/SUP], Garc?a-Sastre A[SUP]6[/SUP], Li S[SUP]7[/SUP], Ward AB[SUP]2[/SUP], Wilson IA[SUP]8[/SUP], Crowe JE Jr[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2019 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] B-lymphocytes; antibodies; antibody-dependent cell cytotoxicity; antigen-antibody reactions; hemagglutinin glycoproteins; influenza A virus; influenza virus; monoclonal; viral
PMID: 31100268 DOI: 10.1016/j.cell.2019.04.011