INHIBITION OF HERPES-SIMPLEX VIRUS TYPE-1 IMMEDIATE-EARLY GENE-EXPRESSION BY ALPHA-INTERFERON IS NOT VP16 SPECIFIC

Pretreatment of tissue culture cells with alpha interferon (IFN-alpha) inhibits the transcription of herpes simplex virus type 1 (HSV-1) imm ediate-early (IE) genes, an effect which has been attributed to reduce d transactivation of IE promoters by the virion protein VP16. Our prev ious demonstration that IFN-alpha inhibited the replication of the HSV -1 mutant in 1814, which has a mutated VP16 unable to activate IE tran scription, appeared to be incompatible with IFN-alpha having an effect on VP16 action (D. R. S. Jamieson, L. H. Robinson, J. I. Daksis, M. J . Nicholl, and C. M. Preston, J. Gen. Virol, 76:1417-1431, 1995). To i nvestigate this observation further, cells were infected with a deriva tive of in 1814 containing the lacZ gene controlled by the human cytom egalovirus IE promoter. The accumulation of HSV-1 IE RNA species was i nhibited by IFN-alpha in these cells to the same extent as in cells in fected with a virus rescued at the VP16 locus, and production of lacZ- specific RNA was also reduced, demonstrating that IFN-alpha can inhibi t expression from a heterologous promoter that is not responsive to VP 16. To provide a means of investigating the activity of VP16 on IE pro moters not located in the HSV-1 genome, cell lines containing the neom ycin phosphotransferase gene controlled by the HSV-1 IE ICP0 promoter were constructed. Activation of the IE promoter by VP16 was not inhibi ted when the ICP0 promoter was resident in the cell, demonstrating tha t VP16 function was unaffected by pretreatment of cells with IFN-alpha . The results suggest that IFN-alpha prevents the onset of IE transcri ption from the HSV-1 genome through a general mechanism rather than by having an effect specific to HSV-1 IE promoters.