T. Komatsu et al., INTERFERON-GAMMA-INDUCED TYPE-I NITRIC-OXIDE SYNTHASE ACTIVITY INHIBITS VIRAL REPLICATION IN NEURONS, Journal of neuroimmunology, 68(1-2), 1996, pp. 101-108
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.