Tromantadine inhibits a late step in herpes simplex virus type 1 replication and syncytium formation

Addition of tromantadine after virus penetration inhibited HSV-1 induced syncytium formation and virus production in HEp-2 and VERO cells and acted additively with neutralizing antibody in blocking virus spread and cytopathology. Inhibition of syncytium formation in VERO cells infected with 0.01 pfu/cell of HSV-1 GC+ was observed at a concentration greater than 25 micrograms/ml. The extent of inhibition was dependent upon the multiplicity of infection and cell type. Tromantadine inhibited a late event in HSV-1 replication which appeared to be sensitive to cycloheximide. Reversal of the inhibitory effect of tromantadine on syncytium formation required new protein synthesis. HSV-1 gB, gC, and gD were synthesized in the presence of tromantadine and could be detected on the cell surface by immunofluorescence. Tromantadine most likely inhibits a cellular process that is required for syncytium formation, such as glycoprotein processing, which occurs after the synthesis of the fusion protein but before its expression on the cell surface.