Sialic Acid as Receptor Determinant of Ortho- and Paramyxoviruses

The designation myxoviruses has been chosen historically for a group of viruses comprising influenza viruses, Newcastle disease virus, and mumps virus, because they were able to interact with mucins (see Chapter 5). A characteristic feature of these viruses was the presence of two activities that appeared to counteract each other. On the one hand, the viruses bind to receptors present on erythrocytes, resulting in a hemagglutination reaction. On the other hand, they contain a receptor-destroying enzyme rendering erythrocytes resistant to the viral agglutinating activity. The receptor determinant recognized by this group of viruses turned out to be sialic acid, and the receptor-destroying enzyme has been characterized as a sialidase and a sialate O-acetylesterase. Despite the similarities, members of the myxovirus group differ in several fundamental aspects, e.g., the presence of a segmented or a nonsegmented genome. Therefore, they have been grouped into two taxonomic families. Influenza A, B, and C viruses belong to the family Orthomyxoviridae. Viruses such as mumps virus, Newcastle disease virus, Sendai virus, and other parainfluenza viruses are members of the family Paramyxoviridae. In addition to the receptor-binding and the receptor-destroying activity, these viruses have a fusion activity. They differ, however, in the distribution of the three activities on the viral surface glycoproteins. With influenza A and B viruses, receptor-binding and fusion activity are functions of the hemagglutinin (HA). A second glycoprotein (NA) is responsible for the sialidase activity. In the case of paramyxoviruses, the receptor-binding and the sialidase activity are combined on one type of glycoprotein designated HN, whereas the fusion activity is localized on a separate glycoprotein (F). Influenza C viruses have only a single glycoprotein that is responsible for all three activities. They also differ from the other viruses in that they recognize N-acetyl-9-O-acetylneuraminic acid (Neu5,9Ac2) rather than N-acetylneuraminic acid (Neu5Ac) as receptor determinant. Furthermore, the receptor-destroying enzyme of influenza C viruses is a sialate 9-O-acetylesterase. In this chapter, the interaction of viral proteins with sialic acid and the biological significance of the receptor-binding and the receptor-destroying activity are discussed.