INHIBITION OF THE NEURAMINIDASE OF PARAMYXOVIRUSES BY HALIDE-IONS - A POSSIBLE MEANS OF MODULATING THE 2 ACTIVITIES OF THE HN-PROTEIN

The paramyxovirus glycoprotein HN has hemagglutinating and neuraminidase activities. The neuraminidase activity of SV5 [simian virus 5] and several other paramyxoviruses is reversibly inhibited by chloride and other halide ions. Kinetic analyses showed that the inhibition was noncompetitive and that the effectiveness of the halides as inhibitors increased with their size. The pH optimum of the SV5 neuraminidase (4.5) was not affected by increasing concentrations of chloride. In contrast to the inhibition of neuraminidase activity, halide ions enhanced hemagglutinating activity and decreased elution from chicken erythrocytes, and the greater the inhibition of neuraminidase the higher the hemagglutination titer. This reciprocal effect on receptor binding and receptor destruction suggests that these 2 opposing activities of the HN glycoprotein can be regulated by environmental conditions such as chloride concentration and pH. Thus virus attachment would be favored by the high chloride concentration and neutral pH found in the extracellular environment and neuraminidase activity by the lower intracellular chloride concentration and pH. The present results and a review of published data suggest that the viral neuraminidase activity that is important for the release and dissemination of maturing virions is expressed before the arrival of viral glycoproteins and glycolipids at the external surface of the plasma membrane.