title: A unique phosphatidylinositol bearing a novel branched-chain fatty acid from Rhodococcus equi binds to influenza virus hemagglutinin and inhibits the infection of cells.
abstract: From the aquatic bacterium Rhodococcus equi strain S(420), we isolated a substance that strongly binds to influenza viruses. Structural analyses revealed that it is a unique type of phosphatidylinositol (PtdIns) bearing a branched-chain fatty acid (14-methyloctadecanoic acid). In a TLC/virus-binding immunostaining assay, this PtdIns bound to all subtypes of hemagglutinin (HA) of influenza A viruses tested, isolated from humans, ducks and swine, and also to human influenza B viruses. Furthermore, the PtdIns significantly prevented the infection of MDCK cells by influenza viruses, and also inhibited the virus-mediated hemagglutination and low pH-induced hemolysis of human erythrocytes, which represents the fusogenic activities of the viral HA. We also used purified hemagglutinin instead of virions to examine the interaction between viral HA and PtdIns, showing that the PtdIns binds to hemagglutinin. These findings indicate that the inhibitory mechanism of PtdIns on the influenza virus infection may be through its binding to viral HA spikes and host cell endosomal/lysosomal membranes, which are mediated by the function of viral HA.
authors.affiliation: Department of Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, Yada, Shizuoka 422-8526, Japan.
authors.forename: C T
authors.initials: CT
authors.lastname: Guo
authors.forename: S
authors.initials: S
authors.lastname: Ohta
authors.forename: A
authors.initials: A
authors.lastname: Yoshimoto
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: K F
authors.initials: KF
authors.lastname: Shortridge
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: D
authors.initials: D
authors.lastname: Miyamoto
authors.forename: K I
authors.initials: KI
authors.lastname: Jwa Hidari
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D004285:Dogs; D004372:Ducks; D005227:Fatty Acids / Q000737:chemistry; D006384:Hemagglutination / Q000187:drug effects; D006389:Hemagglutinins, Viral / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000378:metabolism*; D009981:Influenza B virus / Q000737:chemistry; D007251:Influenza, Human / Q000517:prevention & control*; D007668:Kidney / Q000166:cytology; D009975:Orthomyxoviridae / Q000378:metabolism; D010716:Phosphatidylinositols / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology*; D016929:Rhodococcus equi; D013552:Swine
chemical_list: D005227:Fatty Acids; D006389:Hemagglutinins, Viral; D010716:Phosphatidylinositols