Effect of electric charged molecules on Sindbis virus hemagglutination and hemolysis.

The role of electrostatic interactions in the attachment and fusion at acidic pH of Sindbis virus (SNV) with goose erythrocytes was studied, investigating the effect of several anionic and cationic polyelectrolytes on SNV hemagglutination and hemolysis. In order to establish the target of active drugs, the compounds were incubated either with the virus particles or with the erythrocytes. Dextran sulfate was the only compound able to inhibit the attachment of SNV to the erythrocytes. Fusion of virus with red cells was reduced dose-dependently by the polyanions dextran sulfate, mucin and polygalacturonic acid. On the contrary two polycations, polylysine and polybrene, enhanced viral hemolytic activity. However the effect of polyions is not exclusively related to the electric charge since ineffective molecules were found in both classes of compounds.

Effect of polyions on the early events of Sindbis virus infection of Vero cells.

To clarify the role of electrostatic interactions in the binding of Sindbis virus (SNV) to cell membrane receptors, we investigated the effect of different polyions on the initial steps of infection of Vero cells by the virus. Several polyanions (mucin, heparin, polygalacturonic acid) and polycations (polylysine, protamine, polybrene) were able to reduce the replication of SNV when present in the viral adsorption period, whereas others (chondroitin sulfate, polymyxin B sulfate, histone) were devoid of any activity. Therefore the electric charge alone is not sufficient to explain the action of compounds. The effects of polyions on receptor binding, on bound virus, and on internalized virus have been examined. All the drugs inhibited SNV infection by affecting its binding to the cellular receptor. The results indicated that heparin and mucin act directly on the virus particle while polycations bind to the cell membrane receptor for the virus, protamine being effective on both targets. Since among polyanions glycosaminoglycans showed a strong inhibiting activity, the involvement of these molecules in the virus surface receptor was assessed by enzyme digestion of cell membrane with heparinase and chondroitin ABC lyase.