Differentiation of herpes simplex virus-induced fusion from without and fusion from within by cyclosporin A and compound 48/80

Abstract

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 microM. 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 microM. 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. O-Acetyl cyclosporin A is unable to inhibit FFWI induced by group 2 viruses; in contrast, cyclosporin H and the Ca2+ 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 Ca2+ ions may be preconditions for the observed effects. Binding of cyclosporin A to cyclophilin does not appear to be responsible for these effects.