Treating strains of herpes simplex virus (HSV) in culture with either cyclosporin A or compound 48/80, allowed the strains to be divided into two groups. Group 1 contains the strains ANG and HFEM of HSV-1 and Lux syn (HSV-2) producing fusion from within (FFWI) and fusion from without (FFWO). Cyclosporin A fails to inhibit both types of fusion at concentrations up to 100 µ. Strains ANG and HFEM belong to the syn 3 marker locus group identified for HSV-1. Group 2 contains all other fusion-producing strains of HSV tested so far. Cyclosporin A inhibits FFWI at concentrations as low as 10 to 20 µ. These strains belong to the syn locus marker groups 1, 2, 4 and 5. From the fact that mutations in glycoprotein B belong to the syn 3 marker group we conclude that glycoprotein B is of major importance for FFWO. Compound 48/80 also differentiates between these two groups of viruses. -Acetyl cyclosporin A is unable to inhibit FFWI induced by group 2 viruses; in contrast, cyclosporin H and the Ca ionophore A23187 exert inhibition effects similar to those exerted by cyclosporin A. We conclude from the effects of these compounds that binding properties of the OH group of cyclosporin A and an increase of Ca ions may be preconditions for the observed effects. Binding of cyclosporin A to cyclophilin does not appear to be responsible for these effects.


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