A radical form of nitric oxide suppresses RNA synthesis of rabies virus

Hydrophobia is an incurable disease of the central nervous system. Therefor e, every mode of the immune response is important to inhibit and clear infe ction. Innate immunity such as nitric oxide is significantly upregulated du ring rabies virus infection in vivo. In this report, the possible role of n itric oxide in inhibition of rabies virus replication was studied. Rabies v irus infected neuroblastoma cells were treated with nitric oxide generated from SNP or SNP in the presence of ascorbate. SNP-ascorbate generates mainl y NO. in culture medium while NO+ is the major product of SNP alone. Treatm ent with SNP-ascorbate resulted in delay and suppression of infectious vira l particle production. In contrast, treatment with SNP alone did not interf ere with multiplication of this virus. The mechanism of inhibition by NO wa s at the level of gene expression, which was demonstrated by reduction in t he level of N, G and L gene expression. The effect of SNP-ascorbate generat ed NO on rabies virus protein synthesis was also investigated. Synthesis of N protein in the presence of NO was suppressed which correlated to down re gulation of N gene expression. We hypothesize that one of the roles of NO i n the central nervous system during rabies virus infection is to limit vira l dissemination by down-regulating rabies virus production through transcri ption inhibition. (C) 2001 Published by Elsevier Science B.V.