4xq5
From Proteopedia
Human-infecting H10N8 influenza virus retains strong preference for avian-type receptors
Structural highlights
Function[A0A059T4A1_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.[RuleBase:RU003324][SAAS:SAAS00046810] Publication Abstract from PubMedRecent avian-origin H10N8 influenza A viruses that have infected humans pose a potential pandemic threat. Alterations in the viral surface glycoprotein, hemagglutinin (HA), typically are required for influenza A viruses to cross the species barrier for adaptation to a new host, but whether H10N8 contains adaptations supporting human infection remains incompletely understood. We investigated whether H10N8 HA can bind human receptors. Sialoside glycan microarray analysis showed that the H10 HA retains a strong preference for avian receptor analogs and negligible binding to human receptor analogs. Crystal structures of H10 HA with avian and human receptor analogs revealed the basis for preferential recognition of avian-like receptors. Furthermore, introduction of mutations into the H10 receptor-binding site (RBS) known to convert other HA subtypes from avian to human receptor specificity failed to switch preference to human receptors. Collectively, these findings suggest that the current H10N8 human isolates are poorly adapted for efficient human-to-human transmission. A Human-Infecting H10N8 Influenza Virus Retains a Strong Preference for Avian-type Receptors.,Zhang H, de Vries RP, Tzarum N, Zhu X, Yu W, McBride R, Paulson JC, Wilson IA Cell Host Microbe. 2015 Mar 11;17(3):377-84. doi: 10.1016/j.chom.2015.02.006. PMID:25766296[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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