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The only spike of Influenza C virus, the hemagglutinin-esterase-fusion glycoprotein HEF combines receptor binding, receptor hydrolysis and membrane fusion activities. HEF is S-acylated, but in contrast to HA of Influenza A and B virus, it contains just one acylation site, a cysteine located at the cytosol-facing end of the transmembrane region which contains stearic acid. Previous studies established the essential role of Sacylation of HA for replication of Influenza A and B virus by affecting budding and/or membrane fusion, but the function of acylation of HEF was hitherto not investigated.
Using reverse genetics we rescued a virus containing non-stearoylated HEF, which was stable during serial passage and showed no competitive fitness defect, but the growth rate of the mutant virus was reduced by one log. Acylation of HEF does neither affect the kinetics of its plasma membrane transport nor the protein composition of virus particles. Cryo-electron microscopy showed that the shape of viral particles and the hexagonal array of spikes typical for Influenza C virus were not influenced by this mutation indicating that virus budding was not disturbed. However, the extent and kinetics of hemolysis were reduced in mutant virus suggesting that non-acylated HEF has a defect in membrane fusion.