The receptor-destroying enzyme of influenza C virus is required for entry into target cells

The hemagglutinin-esterase (HE) protein of influenza C viruses possesses an acetylesterase activity, which appears essential for replication, as determined by reduced infectivity after inhibition of the viral enzyme [Vlasak et al., J. Virol. 63, 2056-2062 (1989)]. Analysis revealed the absence of virus-specific RNA and protein synthesis in infected cells after inhibition of the receptor-destroying enzyme. In addition, hemolytic activity was reduced after incubation of influenza C/JJ/50 virus with diisopropyl-fluorophosphate or 3,4-dichloro-isocoumarin. Further analysis revealed that inhibition of hemolysis depends on virus and erythrocyte concentrations. It is suggested that an active receptor-destroying enzyme is required for entry of influenza C virus into target cells at a step prior to fusion of the viral and cellular membrane. Our data indicate that cleavage of receptors bound to the HE protein is a prerequisite for the low pH-triggered conformational change required for fusion.