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CRYSTAL STRUCTURE OF THE A/Ecuador/1374/2016(H3N2) INFLUENZA VIRUS HEMAGGLUTININ WITH HUMAN RECEPTOR ANALOG 6'-SLNLN
Structural highlights
FunctionA0A4P8J8E1_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 either through clathrin-dependent endocytosis or through 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.[HAMAP-Rule:MF_04072] 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.[RuleBase:RU003324] Publication Abstract from PubMedHemagglutinins (HAs) from human influenza viruses descend from avian progenitors that bind alpha2-3-linked sialosides and must adapt to glycans with alpha2-6-linked sialic acids on human airway cells to transmit within the human population. Since their introduction during the 1968 pandemic, H3N2 viruses have evolved over the past five decades to preferentially recognize human alpha2-6-sialoside receptors that are elongated through addition of poly-LacNAc. We show that more recent H3N2 viruses now make increasingly complex interactions with elongated receptors while continuously selecting for strains maintaining this phenotype. This change in receptor engagement is accompanied by an extension of the traditional receptor-binding site to include residues in key antigenic sites on the surface of HA trimers. These results help explain the propensity for selection of antigenic variants, leading to vaccine mismatching, when H3N2 viruses are propagated in chicken eggs or cells that do not contain such receptors. Evolution of human H3N2 influenza virus receptor specificity has substantially expanded the receptor-binding domain site.,Thompson AJ, Wu NC, Canales A, Kikuchi C, Zhu X, de Toro BF, Canada FJ, Worth C, Wang S, McBride R, Peng W, Nycholat CM, Jimenez-Barbero J, Wilson IA, Paulson JC Cell Host Microbe. 2024 Feb 14;32(2):261-275.e4. doi: 10.1016/j.chom.2024.01.003. , Epub 2024 Feb 1. PMID:38307019[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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