Neuronal expression of NOS-1 is required for host recovery from viral encephalitis.
The role of nitric oxide synthase (NOS) in host defense and clearance of vesicular stomatitis virus (VSV) from the central nervous system (CNS) was examined. NOS-1, NOS-2, and NOS-3 knockout mice were infected with VSV and were treated with either IL-12 or medium. IL-12 treatment resulted in substantially decreased VSV titers in wildtype and NOS-3 knockout mice, but had a marginal effect in the NOS-1 and NOS-2 knockout mice. NOS-1 expression in neurons was associated with survival from VSV infection. The data indicate that the enzyme activity is local, since NOS-2 expression in microglia and inflammatory macrophages and NOS-3 expression in astrocytes, endothelial cells, and ependymal cells did not compensate.
Komatsu
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Department of Biology, Center for Neural Science, Kaplan Comprehensive Cancer Center, New York University, 100 Washington Square East, mail code 5181, New York, New York, 10003-6688, USA.
Ireland
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Chen
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Reiss
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D000818:Animals; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000821:virology; D016466:CHO Cells; D006224:Cricetinae; D018792:Encephalitis, Viral / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000821:virology; D007376:Interleukin-2 / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009017:Morbidity; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology*; D009474:Neurons / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000276:immunology*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D018353:Rhabdoviridae Infections / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000254:growth & development / Q000276:immunology*; D015431:Weight Loss
D007376:Interleukin-2; D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse