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

Hydrophobia is an incurable disease of the central nervous system. Therefore, every mode of the immune response is important to inhibit and clear infection. Innate immunity such as nitric oxide is significantly upregulated during rabies virus infection in vivo. In this report, the possible role of nitric oxide in inhibition of rabies virus replication was studied. Rabies virus infected neuroblastoma cells were treated with nitric oxide generated from SNP or SNP in the presence of ascorbate. SNP-ascorbate generates mainly NO* in culture medium while NO(+) is the major product of SNP alone. Treatment with SNP-ascorbate resulted in delay and suppression of infectious viral particle production. In contrast, treatment with SNP alone did not interfere with multiplication of this virus. The mechanism of inhibition by NO was at the level of gene expression, which was demonstrated by reduction in the level of N, G and L gene expression. The effect of SNP-ascorbate generated NO on rabies virus protein synthesis was also investigated. Synthesis of N protein in the presence of NO was suppressed which correlated to down regulation of N gene expression. We hypothesize that one of the roles of NO in the central nervous system during rabies virus infection is to limit viral dissemination by down-regulating rabies virus production through transcription inhibition.