A number of
fatty acids were found to inhibit Sendai virus-induced
hemolysis. cis-
Unsaturated fatty acids such as
oleate, as well as the methyl-branched
isostearate, completely inhibited viral
hemolysis at concentrations as low as 5-10 micrograms/ml, whereas the saturated, normal
acids such as
palmitate and
stearate were comparably inhibitory only at 2-5 times those concentrations. trans-Unsaturated
acids, as well as several other amphiphilic compounds, were either not or only weakly inhibitory. In contrast to their disparate effects on viral
hemolysis, cis- and trans-unsaturated
acids lysed erythrocytes in the same concentration range, which is several times higher than that at which the former compounds inhibited viral
hemolysis. The mechanism of inhibition of viral
hemolysis by
isostearate involves the inactivation of viral hemolytic activity per se, since
isostearate neither inhibited viral hemagglutination nor rendered erythrocytes significantly less susceptible to
hemolysis. Furthermore, the concentration dependence of
hemolysis inhibition by
isostearate was biphasic, increasing sharply at the critical
micelle concentration from a linear relationship below that concentration. Finally, an inhibitory concentration of
isostearate was well below that at which amphiphiles dissolved membranes and did not dissolve Sendai virus, as shown by
sucrose gradient centrifugation and
sodium dodecyl sulfate-
polyacrylamide gel electrophoresis. It was concluded that low concentrations of
fatty acids--particularly cis-unsaturated or fluid-phase types--could block the fusion, as opposed to agglutination, step of viral
hemolysis by perturbing hydrophobic regions of the Sendai virus membrane.