EVIDENCE FOR AN ANTIVIRAL EFFECT OF NITRIC-OXIDE - INHIBITION OF HERPES-SIMPLEX VIRUS TYPE-1 REPLICATION

Nitric oxide (NO) has antimicrobial activity against a wide spectrum o f infectious pathogens, but an antiviral effect has not been reported. The impact of NO, from endogenous and exogenous sources, on herpes si mplex virus type 1 (HSV 1) replication was studied in vitro. HSV 1 rep lication in RAW 264.7 macrophages was reduced 1,806-fold in monolayers induced to make NO by activation with gammaIFN and LPS. A competitive and a noncompetitive inhibitor of nitric oxide synthetase substantial ly reduced the antiviral effect of activated RAW macrophages. S-nitros o-L-acetyl penicillamine (SNAP) is a donor of NO and was added to the media of infected monolayers to assess the antiviral properties of NO in the absence of gammaIFN and LPS. A single dose of S-nitroso-L-acety l penicillamine 3 h after infection inhibited HSV 1 replication in Ver o, HEp2, and RAW 264.7 cells in a dose-dependent manner. Neither viruc idal nor cytocidal effects of NO were observed under conditions that i nhibited HSV 1 replication. Nitric oxide had inhibitory effects, compa rable to that of gammaIFN/LPS, on protein and DNA synthesis as well as on cell replication. This report demonstrates that, among its diverse properties, NO has an antiviral effect.