7t3d
CryoEM map of anchor 222-1C06 Fab and lateral patch 2B05 Fab binding H1 HA
Structural highlights
FunctionC3W5S1_I09A0 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:SAAS013829_004_327643][RuleBase:RU003324] Publication Abstract from PubMedBroadly neutralizing antibodies that target epitopes of haemagglutinin on the influenza virus have the potential to provide near universal protection against influenza virus infection(1). However, viral mutants that escape broadly neutralizing antibodies have been reported(2,3). The identification of broadly neutralizing antibody classes that can neutralize viral escape mutants is critical for universal influenza virus vaccine design. Here we report a distinct class of broadly neutralizing antibodies that target a discrete membrane-proximal anchor epitope of the haemagglutinin stalk domain. Anchor epitope-targeting antibodies are broadly neutralizing across H1 viruses and can cross-react with H2 and H5 viruses that are a pandemic threat. Antibodies that target this anchor epitope utilize a highly restricted repertoire, which encodes two public binding motifs that make extensive contacts with conserved residues in the fusion peptide. Moreover, anchor epitope-targeting B cells are common in the human memory B cell repertoire and were recalled in humans by an oil-in-water adjuvanted chimeric haemagglutinin vaccine(4,5), which is a potential universal influenza virus vaccine. To maximize protection against seasonal and pandemic influenza viruses, vaccines should aim to boost this previously untapped source of broadly neutralizing antibodies that are widespread in the human memory B cell pool. Broadly neutralizing antibodies target a haemagglutinin anchor epitope.,Guthmiller JJ, Han J, Utset HA, Li L, Lan LY, Henry C, Stamper CT, McMahon M, O'Dell G, Fernandez-Quintero ML, Freyn AW, Amanat F, Stovicek O, Gentles L, Richey ST, de la Pena AT, Rosado V, Dugan HL, Zheng NY, Tepora ME, Bitar DJ, Changrob S, Strohmeier S, Huang M, Garcia-Sastre A, Liedl KR, Bloom JD, Nachbagauer R, Palese P, Krammer F, Coughlan L, Ward AB, Wilson PC Nature. 2022 Feb;602(7896):314-320. doi: 10.1038/s41586-021-04356-8. Epub 2021 , Dec 23. PMID:34942633[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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