Respiratory mucus as a virus-host range determinant

Efficient penetration of the mucus layer is needed for respiratory viruses to avoid mucociliary clearance prior to infection. Many respiratory viruses bind to glycans on the heavily glycosylated mucins that give mucus its gel-like characteristics. Influenza viruses, some paramyxoviruses, and coronaviruses avoid becoming trapped in the mucus by releasing themselves by means of their envelope-embedded enzymes that destroy glycan receptors. For efficient infection, receptor binding and destruction need to be in balance with the host receptor repertoire. Establishment in a novel host species requires resetting of the balance to adapt to the different glycan repertoire encountered. Growing understanding of species-specific mucosal glycosylation patterns and the dynamic interaction with respiratory viruses identifies the mucus layer as a major host-range determinant and barrier for zoonotic transfer. The mucus layer of the respiratory tract forms a barrier against viruses.Mucins, which are heavily glycosylated in a species-specific manner, form the major structural and functional component of mucus.Glycan-binding viruses may avoid immobilization in mucus by carrying receptor-destroying enzymes.To successfully breach the host species barrier, (zoonotic) viruses must reset the functional balance between binding and cleaving of glycan receptors.