Structure and Function of the Hef Glycoprotein of Influenza C Virus

Soon after the first isolation of an influenza C virus from a patient, it became obvious that this virus differs from other myxoviruses in several aspects. Pronounced differences have been observed in the interactions between the virus and cell surfaces, suggesting that influenza C virus attaches to the receptors different from those recognized by other myxoviruses. While influenza A and B viruses agglutinate erythrocytes from many species, including humans, the spectrum of erythrocytes agglutinated by influenza C virus is much more restricted. Erythrocytes from rats, mice, and adult chickens are suitable for hemagglutination and hemadsorption tests; cells from other species, however, react not at all or only poorly with influenza C virus. Differences are also observed so far as hemagglutination inhibitors are concerned. A variety of glycoproteins have been shown to prevent influenza A and B viruses from agglutinating erythrocytes. In the case of influenza C virus, rat serum was for a long time the only known hemagglutination inhibitor. A difference in the receptors for influenza C virus and other myxo-viruses was also suggested by studies on the receptor-destroying enzyme. The ability of influenza C virus to inactivate its own receptors was reported soon after the first isolation of this virus from a patient. However, the influenza C enzyme did not affect the receptors of other myxoviruses and, conversely, the receptor-destroying enzyme of either of the latter viruses was unable to inactivate the receptors for influenza C virus on erythrocytes. While the enzyme of influenza A and B virus was characterized as a neuraminidase in the 1950s, even with refined methodology no such activity was detectable with influenza C virus. It is now known that both the receptor-binding and receptor-destroying activities, as well as the fusion activity of influenza C virus are mediated by the only glycoprotein present on the surface of the virus particle. The structure and functions of this protein, which is designated as HEF, are reviewed in this chapter.