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The H1N1 mutant, Y161F, causes increased viral growth in Madin-Darby canine kidney and Vero cells, two cell lines commonly used in the production of influenza vaccines. This Y161F mutation not only increases the thermal stability of HA, but also enhances its binding affinity for α2,6- and α2,3-linked Neu5Ac. Vaccine strains with the Y161F mutation in HA may increase vaccine yield in mammalian cell culture systems. Human influenza A/B viruses are unusual in preferring alpha 2-6-linked Sias, undergoing a switch from alpha 2-3 linkage preference during adaptation from animals to humans. This correlates with the expression of alpha 2-6-linked Sias on ciliated human airway epithelial target cells and of alpha 2-3-linked Sias on secreted soluble airway mucins, which are unable to inhibit virus binding.