The comparative anti-herpes simplex virus effects of human interferons.

The mechanism(s) of anti-herpes simplex virus (HSV) activity of interferons (IFNs) have not been clearly identified. We have tested natural and recombinant human IFN-alpha, IFN-beta, and IFN-gamma preparations for their relative anti-HSV activity in human corneal and Vero monkey kidney cells. The relative anti-HSV activities in corneal cells were IFN-beta > rIFN-gamma > IFN-alpha (lymphoblastoid) > rIFN-beta2a = rIFN-alphaA/D. IFN-beta at 100 IU/ml reduced virus yield by 59+/-24%. The relative anti-HSV activity in Vero cells was rIFN-gamma > IFN-beta = IFN-alpha (lymphoblastoid) > rIFN-alphaA/D > rIFN-alpha2a. IFN-gamma at 100 IU/ml reduced virus yields by 90+/-4%. Reducing the multiplicity of infection significantly increased the apparent antiviral activity of all IFNs. The antiviral activity of IFNs could be detected by 4 h after treatment of Vero cells but not until 8 h in corneal cells. Western blot analysis showed that none of the IFNs detectably reduced the levels of immediate-early HSV protein, ICP4, but some reduced ICP0 levels early during infection, the extent and duration of the reduction varying with both IFN and cell type. The greatest effects on viral protein levels were detected in IFN-y-treated Vero cells. These data indicated that the targets of the anti-HSV activities of IFNs can vary with both IFN and cell type.