Hemagglutinin and neuraminidase as determinants of influenza virus pathogenicity

The pathogenicity of influenza viruses is determined by many of its other biological properties, such as efficiency of replication, tissue tropism, host range, spread of infection, as well as response to and modulation of host defense. All of these properties are controlled by the complex interplay of viral and host factors at virtually each stage in the life cycle of the virus. Activation of the hemagglutinin by host cell proteases has been shown in many studies to have a dramatic effect on pathogenesis, and the molecular details of proteolytic activation are well understood [16a]. We will concentrate here on recent studies in which we have analyzed the interplay of hemagglutinin (HA) and neuraminidase (NA) in receptor binding and release and some of the factors that determine spread of infection in the organism.