Role of the Na+,K+ pump in herpes simplex type 1-induced cell fusion: melittin causes specific reversion of syncytial mutants with the syn1 mutation to Syn+ (wild-type) phenotype.

To evaluate the importance of the Na+,K+ pump and ionic gradients in virus-induced cell fusion, we investigated the effects of melittin, a 26 amino acid bioactive peptide found in honey bee venom, on cell fusion caused by HSV-1 syncytial mutants. Melittin inhibited fusion of Vero cells caused by HSV-1 mutant viruses mP(MP), KOS (syn20) and KOS (FFV3) containing the syncytial mutation syn1 in glycoprotein K. However, it did not affect cell fusion caused by mutants HFEM(tsB5) or KOS amb1511-7 with mutations in glycoprotein B. Melittin caused specific reversion of syn1 mutant virus plaques to syn+ (wild-type) plaque morphology, and inhibited virus adsorption and penetration. It also inhibited the Na+,K+ pump activity, and the binding of 3H-ouabain to the Na+,K+ pump of infected Vero cells. The Na+,K+ pump activity of infected Vero cells in comparison to mock-infected cells was significantly decreased. Ouabain, a specific inhibitor of the Na+,K+ pump, inhibited fusion of Vero cells caused by all syncytial virus strains.