9b2m
Hemagglutinin H1 New Caledonia 1999 in complex with monoclonal antibody Fab 43_S0008
Structural highlights
FunctionQ6WG00_9INFA Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore (By similarity).[SAAS:SAAS00204388] Publication Abstract from PubMedAntibodies targeting epitopes through germline-encoded motifs can be found in different individuals. While these public antibodies are often beneficial, they also pose hurdles for subdominant antibodies to emerge. Here, we use transgenic mice that reproduce the human IGHV1-69( *)01 germline-encoded antibody response to the conserved stem epitope on group 1 hemagglutinin (HA) of influenza A virus to show that this germline-endowed response can be overridden by a subdominant yet cross-group reactive public antibody response. Immunization with a non-cognate group 2 HA stem enriched B cells harboring the IGHD3-9 gene, thereby switching from IGHV1-69- to IGHD3-9-encoded motif-dependent epitope recognition. These IGHD3-9 antibodies bound, neutralized, and conferred cross-group protection in mice against influenza A viruses. A cryoelectron microscopy (cryo-EM) structure of an IGHD3-9 antibody resembled the human broadly neutralizing antibody FI6v3, which uses IGHD3-9. Together, our findings offer insights into vaccine regimens that engage an immunoglobulin repertoire with broader cross-reactivity to influenza A viruses. Modulating the immunodominance hierarchy of immunoglobulin germline-encoded structural motifs targeting the influenza hemagglutinin stem.,Ataca S, Sangesland M, de Paiva Froes Rocha R, Torrents de la Pena A, Ronsard L, Boyoglu-Barnum S, Gillespie RA, Tsybovsky Y, Stephens T, Moin SM, Lederhofer J, Creanga A, Andrews SF, Barnes RM, Rohrer D, Lonberg N, Graham BS, Ward AB, Lingwood D, Kanekiyo M Cell Rep. 2024 Nov 22;43(12):114990. doi: 10.1016/j.celrep.2024.114990. PMID:39580804[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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