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. Im munocytochemical staining of NB41A3 cells indicates constitutive expre ssion of interferon (IFN)-gamma receptor and type I NOS. IFN-gamma tre atment of NB41A3 cells increased NO production and type 1 NOS protein. In vitro replication of VSV, polio virus type 1, and Herpes Simplex v irus type 1 (HSV-1) is significantly inhibited by IFN-gamma induced ty pe I NOS and antagonized by NOS inhibitors. In contrast, while IFN-gam ma treatment inhibited influenza and Sindbis virus replication, a diff erent pathway(s) was involved. The isoform-selective NOS inhibitor, 7- nitroindazole (7NI) was used to treat mice, resulting in a 10-fold hig her titer of virus in brain homogenates, and abrogated the recovery-pr omoting effect of interleukin-12 treatment. Thus, IFN-gamma induced ty pe I NOS activity may play an important role in host immunity against neurotropic viral infections.