Synergistic antiherpes virus activity of acyclovir and interferon in human corneal stromal cells

Synergistic anti-herpes simplex virus type 1 (HSV-1) activity between acyclovir (ACV) and recombinant human interferon alpha A2 (IFN) was detected in cell cultures derived from human corneas. This activity was demonstrated when cells were infected at high multipicities of infection (5 pfu/cell) in both cytopathic effect reduction and yield reduction assays as well as in plaque reduction assays at low multiplicities. The synergistic effects occurred over a 30-fold range of concentrations of IFN (6-200 IU/ml) and ACV (0.15-5 microM) at various ratios of the drugs. The augmentation of antiviral activity was greatest when cells were treated with IFN prior to infection and ACV following infection. The addition of IFN after infection, with simultaneous ACV treatment, also resulted in enhanced anti-HSV-1 activity. The combination of IFN with ACV did not increase the cytotoxicity of ACV. The synergistic antiviral activity in corneal cells may account for the previously reported enhanced efficacy of combined treatment with IFNs and nucleoside analogs for therapy of herpetic keratitis.