AN AMPHIPATHIC ALPHA-HELICAL SYNTHETIC PEPTIDE ANALOG OF MELITTIN INHIBITS HERPES-SIMPLEX VIRUS-1 (HSV-1)-INDUCED CELL-FUSION AND VIRUS SPREAD

The effects of hecate, a 23-amino acid synthetic peptide analogue of m elittin, on HSV-1-induced cell fusion and Virus multiplication was inv estigated. Hecate completely inhibited cell fusion induced by HSV-1 sy ncytial(syn) mutants HSV-1 HFEM (tsB5) and HSV-1 mp (MP) at a concentr ation of 5.0 mu M. Metabolic labeling experiments indicated that hecat e did not adversely affect cellular growth and protein synthesis. The synthesis of virus-specified glycoproteins B, C, D, and H was reduced in the presence of hecate; however, the transport of these glycoprotei ns to the surface of infected cells was not affected. Production of in fectious virions for wild-type and syn mutants tsB5 and MP was reduced in the presence of hecate. The effect of hecate on virus titer was de pendent on the multiplicity of infection. Virus titers were reduced 2- 28-fold at an M.O.I. of 0.1, 3-6-fold at an M.O.I. of 0.5, and 0-2.5-f old at an M.O.I. of 2.5. Direct treatment of semipurified virions with hecate reduced titers by approximately 4-fold for KOS, 2-fold for tsB 5, and over 30-fold for MP. (C) 1997 Elsevier Science Inc.