Inducible nitric oxide synthase inhibition delays death of rabies virus-infected mice

A pathophysiological mechanism of cerebral damage and impairment of neurona l function during rabies virus infection was examined, Synthesis of nitric oxide (NO) and expression of the inducible nitric oxide synthase (iNOS) gen e are strongly upregulated during rabies virus infection. Treatment of rabi es virus-infected mice with a selective inhibitor of iNOS, aminoguanidine ( AG), significantly delayed their death. Prolonged survival was not due to s uppression of an inflammatory response in the central nervous system, One e ffect of iNOS inhibition was at the level of viral replication. Treatment w ith AG delayed rabies virus replication by 2 days. Moreover, iNOS inhibitio n also suppressed an early phase of expression of an apoptotic gene, Caspas e-1, which resulted in slow progression of infected cells into apoptotic de ath. iNOS inhibition had no effect on expression of the anti-apoptotic gene , bcl-2, In conclusion, iNOS inhibition delayed the death of rabies virus-i nfected mice by affecting viral replication and apoptotic death of infected cells.