Kinetically differentiating influenza hemagglutinin fusion and hemifusion machines. 2003

Aditya Mittal, and Eugenia Leikina, and Leonid V Chernomordik, and Joe Bentz
Department of Bioscience and Biotechnology, Drexel University, Philadelphia, Pennsylvania 19104, USA.

Membrane fusion mediated by influenza virus hemagglutinin (HA) yields different phenotypes depending on the surface density of activated HAs. A key question is whether different phenotypes arise from different fusion machines or whether different numbers of identical fusion machines yield different probabilistic outcomes. If fusion were simply a less probable event than hemifusion, requiring a larger number of identical fusion machines to occur first, then two predictions can be made. First, fusion should have a shorter average delay time than hemifusion, since there are more machines. Second, fusion should have a longer execution time of lipid mixing after it begins than hemifusion, since the full event cannot be faster than the partial event. Using a new automated video microscopy technique, we simultaneously monitored many HA-expressing cells fusing with erythrocytes and identified individual cell pairs with either full or only partial redistribution of fluorescent lipids. The full lipid mixing phenotype also showed contents mixing, i.e., fusion. Kinetic screening of the digitized fluorescence data showed that the execution of lipid mixing after the onset is faster for fusion than hemifusion. We found no correlation between the delay times before the onset of lipid mixing and the final fusion phenotype. We also found that the execution time for fusion was faster than that for hemifusion. Thus, we provide the first experimental evidence for fusion and hemifusion arising from different machines.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008055 Lipids A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed) Lipid
D008561 Membrane Fusion The adherence and merging of cell membranes, intracellular membranes, or artificial membranes to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. Fusion, Membrane,Fusions, Membrane,Membrane Fusions
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
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D004912 Erythrocytes Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN. Blood Cells, Red,Blood Corpuscles, Red,Red Blood Cells,Red Blood Corpuscles,Blood Cell, Red,Blood Corpuscle, Red,Erythrocyte,Red Blood Cell,Red Blood Corpuscle
D006388 Hemagglutinins Agents that cause agglutination of red blood cells. They include antibodies, blood group antigens, lectins, autoimmune factors, bacterial, viral, or parasitic blood agglutinins, etc. Isohemagglutinins,Exohemagglutinins,Hemagglutinin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D001703 Biophysics The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things. Mechanobiology

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