Cyclosporine A inhibits herpes simplex virus-induced cell fusion but not virus penetration into cells

The effects of the immunosuppressive peptide cyclosporine A on virus-induced cell fusion and virus penetration into cells were studied. Cyclosporine totally inhibited polykaryocyte formation by a syncytial strain of HSV-1 (MP). In contrast, a number of other hydrophobic peptides which inhibit the replication of orthomyxo- and paramyxoviruses and which were less effective in inhibiting fusion in model systems had little effect on HSV-induced cell fusion. Virus replication as measured by the yield of infectious virus and by incorporation of [ 35S]methionine into viral proteins was unaffected by treating cells with cyclosporine. Cyclosporine did not quantitatively inhibit cells surface expression of HSV glycoproteins or plaque formation of syncytial or nonsyncytial virus strains. However, plaques formed by HSV-1 (MP) on cyclosporine-treated monolayers were smaller than those on untreated monolayers and were morphologically similar to plaques produced by the nonsyncytial HSV strain F. Surprisingly, cyclosporine did not inhibit penetration of HSV, a process also thought to involve membrane fusion. Therefore, HSV-1-induced cell fusion and penetration of virus into cells either proceed by mutually exclusive mechanisms or are differentially sensitive to cyclosporine.