title: [Function of glycochains in virus infection].
abstract: Influenza A virus (IAV) has two envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). HA binds to sialic acids at the terminals of glycochains on the host cell surface as virus receptors. NA shows sialidase activity, which cleaves sialic acids from the terminals of glycochains. A new subtype (antigenicities of HA and NA) of IAV for humans has pandemic potential. We investigated the functions of HA and NA in IAV replication and pandemic potential in terms of glycoscience. We found that the sialidase activity of pandemic IAV had low pH stability, which enhanced IAV replication. It is thought that the low pH stability contributed to the pandemics in 1968 and 2009. HA also binds to sulfatide not containing sialic acid, and we found that sulfatide enhanced IAV replication. Binding of HA to sulfatide on the host cell surface enhanced progeny IAV formation in infected cells through the induction of the nuclear export of viral ribonucleoproteins by apoptosis. Sialic acid species are divided into N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). The HAs of some human IAVs bind not only to Neu5Ac but also to Neu5Gc, which may facilitate the occurrence of a human IAV-based pandemic by genetic reassortment among IAV genomes in pig tracheas expressing Neu5Gc. We identified the amino acid residues of human IAV HA responsible for Neu5Gc binding and developed new techniques for the sensitive detection of IAV receptor specificities and infected cells. Our "glycovirology" research will provide new insights into the mechanisms of IAV replication and pandemic potential.
authors.affiliation: Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D016679:Genome, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism; D011485:Protein Binding
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; C483468:hemagglutinin, human influenza A virus; D009439:Neuraminidase