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.
Department of Veterinary Microbiology and Parasitology, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803.
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Baghian
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Kousoulas
D000818:Animals; D002459:Cell Fusion / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008555:Melitten / Q000494:pharmacology*; D010042:Ouabain / Q000378:metabolism; D018139:Simplexvirus / Q000235:genetics / Q000254:growth & development*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology*; D014709:Vero Cells; D010948:Viral Plaque Assay; D014771:Virion / Q000302:isolation & purification
D008555:Melitten; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase