Interferon-gamma induced type I nitric oxide synthase activity inhibits viral replication in neurons.
Type I NOS expression increases in OB neurons during VSV infection. Immunocytochemical staining of NB41A3 cells indicates constitutive expression of interferon (IFN)-gamma receptor and type I NOS. IFN-gamma treatment of NB41A3 cells increased NO production and type I NOS protein. In vitro replication of VSV, polio virus type I, and Herpes Simplex virus type I (HSV-1) is significantly inhibited by IFN-gamma induced type I NOS and antagonized by NOS inhibitors. In contrast, while IFN-gamma treatment inhibited influenza and Sindbis virus replication, a different pathway(s) was involved. The isoform-selective NOS inhibitor. 7-nitroindazole (7NI) was used to treat mice, resulting in a 10-fold higher titer of virus in brain homogenates, and abrogated the recovery-promoting effect of interleukin-12 treatment. Thus, IFN-gamma induced type I NOS activity may play an important role in host immunity against neurotropic viral infections.
Komatsu
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Department of Biology, New York University, NY 10003, USA.
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Reiss
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D000818:Animals; D001254:Astrocytoma; D001483:Base Sequence; D018259:Herpesvirus 1, Human / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D009474:Neurons / Q000737:chemistry / Q000201:enzymology* / Q000821:virology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000276:immunology / Q000378:metabolism*; D017955:Poliovirus / Q000502:physiology; D017471:Receptors, Interferon / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014779:Virus Replication
D017471:Receptors, Interferon; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase