Inducible nitric oxide synthase inhibition delays death of rabies virus-infected mice.
A pathophysiological mechanism of cerebral damage and impairment of neuronal function during rabies virus infection was examined. Synthesis of nitric oxide (NO) and expression of the inducible nitric oxide synthase (iNOS) gene are strongly upregulated during rabies virus infection. Treatment of rabies virus-infected mice with a selective inhibitor of iNOS, aminoguanidine (AG), significantly delayed their death. Prolonged survival was not due to suppression of an inflammatory response in the central nervous system. One effect of iNOS inhibition was at the level of viral replication. Treatment with AG delayed rabies virus replication by 2 days. Moreover, iNOS inhibition also suppressed an early phase of expression of an apoptotic gene, Caspase-1, which resulted in slow progression of infected cells into apoptotic death. iNOS inhibition had no effect on expression of the anti-apoptotic gene, bcl-2. In conclusion, iNOS inhibition delayed the death of rabies virus-infected mice by affecting viral replication and apoptotic death of infected cells.
Sukathida
S
Ubol
Chareeporn
C
Sukwattanapan
Department of Microbiology, Faculty of Science and *Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Yaowapa
Y
Maneerat
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000821:virology; D020169:Caspases / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019254:Genes, bcl-2; D006146:Guanidines / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000032:analysis; D011818:Rabies / Q000188:drug therapy* / Q000401:mortality; D014779:Virus Replication / Q000187:drug effects
D004791:Enzyme Inhibitors; D006146:Guanidines; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020169:Caspases; C004479:pimagedine