Target cell membrane sialic acid modulates both binding and fusion activity of influenza virus. 1995

M C de Lima, and J Ramalho-Santos, and D Flasher, and V A Slepushkin, and S Nir, and N Düzgüneş
Department of Microbiology, School of Dentistry, University of the Pacific, San Francisco, CA 94115-2399, USA.

Influenza virus binds to cell surface sialic acid receptors, and following endocytosis fuses with the endosome membrane at low pH. Whether sialic acid plays a role in the virus-cell membrane fusion step is not known. We investigated the effect of the removal of cell membrane sialic acid on the fusion activity of influenza virus (A/PR/8/34 strain) toward human T lymphocytic leukemia (CEM) cells at low pH. Fusion was monitored by fluorescence dequenching of octadecylrhodamine incorporated in the virus membrane. Removal of sialic acid by neuraminidase resulted in a drastic reduction in both viral binding and fusion. The association of the virus with neuraminidase-treated cells was enhanced at pH 5, compared to that at neutral pH, probably due to the unfolding of the hemagglutinin and the resulting increase in viral surface hydrophobicity, but the fusion capacity of the virus was reduced significantly. The results were analysed with a mass-action kinetic model which could explain and predict the kinetics of fusion. Our results indicate that binding of influenza virus to sialic acid residues on the cell surface leads to rapid and extensive fusion and partially inhibits the low pH-induced viral inactivation.

UI MeSH Term Description Entries
D009439 Neuraminidase An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) Sialidase,Exo-alpha-Sialidase,N-Acylneuraminate Glycohydrolases,Oligosaccharide Sialidase,Exo alpha Sialidase,Glycohydrolases, N-Acylneuraminate,N Acylneuraminate Glycohydrolases,Sialidase, Oligosaccharide
D009975 Orthomyxoviridae A family of RNA viruses causing INFLUENZA and other respiratory diseases. Orthomyxoviridae includes INFLUENZAVIRUS A; INFLUENZAVIRUS B; INFLUENZAVIRUS C; INFLUENZAVIRUS D; ISAVIRUS; and THOGOTOVIRUS. Influenza Viruses,Myxoviruses,Orthomyxoviruses,Influenza Virus,Myxovirus,Orthomyxovirus
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D012794 Sialic Acids A group of naturally occurring N-and O-acyl derivatives of the deoxyamino sugar neuraminic acid. They are ubiquitously distributed in many tissues. N-Acetylneuraminic Acids,Acids, N-Acetylneuraminic,Acids, Sialic,N Acetylneuraminic Acids
D019158 N-Acetylneuraminic Acid An N-acyl derivative of neuraminic acid. N-acetylneuraminic acid occurs in many polysaccharides, glycoproteins, and glycolipids in animals and bacteria. (From Dorland, 28th ed, p1518) Sialic Acid,Acid, N-Acetylneuraminic,Acid, Sialic,N Acetylneuraminic Acid

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