THE EFFECTS OF INTERFERON-ALPHA AND ACYCLOVIR ON HERPES-SIMPLEX VIRUSTYPE-1 RIBONUCLEOTIDE REDUCTASE

Herpes simplex virus-type 1 (HSV-1) encodes both the small (UL40) and large (UL39) subunits of the enzyme, ribonucleotide reductase. Treatme nt of HSV-l-infected cells with interferon-alpha (IFN-alpha) reduced t he levels of both enzyme subunits. Reduced steady state levels of the large subunit were demonstrated by immunoblot using polyclonal antibod y specific for the viral enzyme. Reduction in the amount of small subu nit was shown by a reduction in the electron spin resonance signal der ived from the iron-containing tyrosyl free-radical present in this sub unit. Treatment of cells with 100 IU/ml of IFN-alpha decreased levels of both subunits resulting in a reduction in enzyme activity as measur ed by conversion of CDP to dCDP. The decrease in the amount of the lar ge subunit was not due to a reduction in the level of its mRNA. The co mbination of IFN-alpha and ACV treatment of human cornea stromal cells did not result in a further reduction in amounts of ribonucleotide re ductase relative to that detected with IFN-alpha alone. The IFN-alpha- induced reduction in ribonucleotide reductase activity is the likely c ause of decreased levels of dGTP which we have previously demonstrated in IFN-alpha-treated, infected cells. (C) 1998 Elsevier Science B.V. All rights reserved.