Enhancement of virus induced cell fusion by phytohemagglutinin

The binding of lectins to the cell surface can significantly alter the cellular response to virus infection. A striking example of the ability of lectins to alter virus host cell interactions concerns their effect on virus induced cell fusion. Treatment of cultured mammalian cells with concanavalin A (Con A), wheat germ agglutinin, and soybean agglutinin has been shown to inhibit their subsequent fusion by both RNA and DNA containing viruses. In contrast, treatment of cells with phytohemagglutinin (PHA), a lectin obtained from the red kidney bean (Phaseolus vulgaris), results in significant enhancement of virus induced cell fusion. In this article the authors describe how this property of PHA can be exploited to enhance the efficiency of cell fusion by inactivated viruses to increase the yield of hybrid cells produced by fusion of different cell types. In brief, the cell fusion enhancing activity of PHA is predominantly a property of a single protein, which corresponds to L PHAP. By ion exchange chromatography and polyacrylamide gel electrophoresis 2 major biologic fractions have been isolated. The L PHAP is a homogeneous single protein with potent leukoagglutinin activity but low erythroagglutinin activity, while the H PHAP fraction is a complex protein mixture with high erythroagglutinin activity but little or no leukoagglutinin activity. Both L PHAP and H PHAP possess mitogenic activity. In addition, assay of PHA isolated on thyroglobulin Sepharose has shown that more than 80% of the cell fusion enhancing activity found in PHA is associated with material in the high salt eluate. This material possesses only very low erythroagglutinating activity and by gel electrophoresis is found to be largely devoid of cathodal migrating proteins. These observations lend further support to the conclusion that cell fusion enhancing activity of PHA is a property of the most anodal of the PHA isolectins, which, in addition to its effect on cell fusion, is also a potent leukoagglutinin and mitogen.