title: Role of sulfatide in influenza A virus replication.
abstract: Sulfatide is a 3-O-sulfated galactosylceramide that is abundantly expressed in the gastrointestinal tract, kidney, trachea, and particularly the central nervous system. Cellular sulfatide is mainly localized in the Golgi apparatus, cellular membrane, and lysosomes in cytosol. Since our earlier report showed that the influenza A virus specifically binds to sulfatide, we have investigated the roles of sulfatide in the influenza A virus lifecycle. The viral binding is independent of sialic acids, which function as virus receptors in virus attachment to the host cell surface. Sulfatide is recognized by the ectodomain of the viral envelope glycoprotein hemagglutinin (HA). Nascent HA is transported on the surface membrane of infected cells. The binding of HA with sulfatide on the cell surface induces apoptosis through potential loss of the mitochondrial membrane and nuclear translocation of apoptosis-inducing factor in mitochondria, where PB1-F2 peptide from the viral gene is accumulated. In the nucleus of infected cells, viral ribonucleoprotein (vRNP) complexes are formed from viral RNA genomes, viral nucleoprotein, and viral RNA polymerase subunits, and these complexes are selectively exported into cytosol through the nuclear membrane. The apoptosis significantly enhances the nuclear export of vRNP complexes, resulting in efficient formation of progeny viruses and facilitation of virus replication. At that time, activation of the Raf/mitogen-activated protein extracellular kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway through sulfatide is associated with virus replication. Our studies have demonstrated that sulfatide is not a viral receptor for virus infection, and that the binding of HA with sulfatide functions as an initiation switch for the formation of progeny viruses.
authors.affiliation: Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka.
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D017209:Apoptosis; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006388:Hemagglutinins / Q000378:metabolism; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity*; D007251:Influenza, Human / Q000821:virology*; D008928:Mitochondria / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D013433:Sulfoglycosphingolipids / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
chemical_list: D006388:Hemagglutinins; D012367:RNA, Viral; D012261:Ribonucleoproteins; D013433:Sulfoglycosphingolipids; D014764:Viral Proteins; D048049:Extracellular Signal-Regulated MAP Kinases