A unique phosphatidylinositol bearing a novel branched-chain fatty acid from Rhodococcus equi binds to influenza virus hemagglutinin and inhibits theinfection of cells

From the aquatic bacterium Rhodococcus equi strain S-420, we isolated a sub stance that strongly binds to influenza viruses. Structural analyses reveal ed that it is a unique type of phosphatidylinositol (PtdIns) bearing a bran ched-chain fatty acid (14-methyloctadecanoic acid). In a TLC/virus-binding immunostaining assay, this PtdIns bound to all subtypes of hemagglutinin (H A) of influenza A viruses tested, isolated from humans, ducks and swine, an d also to human influenza B viruses. Furthermore, the PtdIns significantly prevented the infection of MDCK cells by influenza viruses, and also inhibi ted the virus-mediated hemagglutination and low pH-induced hemolysis of hum an erythrocytes,,which represents the fusogenic activities of the viral HA. We also used purified hemagglutinin instead of virions to examine the inte raction between viral EIA and PtdIns, showing that the PtdIns binds to hema gglutinin. These findings indicate that the inhibitory mechanism of PtdIns on the influenza virus infection may be through its binding to viral HA spi kes and host cell endosomal/lysosomal membranes, which are mediated by the function of viral HA.