A unique phosphatidylinositol bearing a novel branched-chain fatty acid from Rhodococcus equi binds to influenza virus hemagglutinin and inhibits the infection of cells.
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.
Guo
C T
CT
Department of Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, Yada, Shizuoka 422-8526, Japan.
Ohta
S
S
Yoshimoto
A
A
Nakata
K
K
Shortridge
K F
KF
Takahashi
T
T
Suzuki
T
T
Miyamoto
D
D
Jwa Hidari
K I
KI
Suzuki
Y
Y
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
D005227:Fatty Acids; D006389:Hemagglutinins, Viral; D010716:Phosphatidylinositols