4dj6
Structure of the hemagglutinin from a highly pathogenic H7N7 influenza virus
Structural highlights
FunctionQ6VMK1_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).[RuleBase:RU003324][SAAS:SAAS013829_004_327643] Publication Abstract from PubMedRecurrence of highly pathogenic avian influenza (HPAI) subtype H7 in poultry continues to be a public health concern. In 2003, an HPAI H7N7 outbreak in the Netherlands infected 89 people in close contact with affected poultry and resulted in one fatal case. In previous studies, the virus isolated from this fatal case, A/Netherlands/219/2003 (NL219) caused a lethal infection in mouse models and had increased replication efficiency and a broader tissue distribution than non-lethal isolates from the same outbreak. A mutation which introduces a potential glycosylation site at Asn123 in the NL219 hemagglutinin was postulated to contribute to the pathogenic properties of this virus. To study this further, we have expressed the NL219 hemagglutin in a baculovirus expression system and performed a structural analysis of the hemagglutinin in complex with avian and human receptor analogs. Glycan microarray and kinetic analysis were performed to compare the receptor binding profile of the wild type recombinant NL219 HA to a variant with a Threonine to Alanine mutation at position 125, resulting in loss of the glycosylation site at Asn123. Results suggest that the additional glycosylation sequon increases binding affinity to avian-type alpha2-3-linked sialosides rather than switching to a human-like receptor specificity and highlight the mechanistic diversity of these pathogens which calls attention to the need for further studies to fully understand the unique properties of these viruses. Structure and receptor complexes of the hemagglutinin from a highly pathogenic H7N7 influenza virus.,Yang H, Carney PJ, Donis RO, Stevens J J Virol. 2012 Jun 6. PMID:22674977[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
