MICE LACKING INDUCIBLE NITRIC-OXIDE SYNTHASE ARE MORE SUSCEPTIBLE TO HERPES-SIMPLEX VIRUS-INFECTION DESPITE ENHANCED TH1 CELL RESPONSES

Mice deficient in the inducible nitric-oxide synthase (iNOS), construc ted by gene-targeting, were significantly more susceptible to herpes s implex virus (HSV)-1 infection, displayed a delayed clearance of virus from the dorsal root ganglia (DRG) and exhibited an increase in the f requency of virus reactivation in DRG compared with similarly infected heterozygous mice, The infected iNOS-deficient mice developed enhance d Th1-type immune responses and their spleen cells produced higher con centrations of IL-12 than similarly infected heterozygous mice. This f inding suggests that iNOS plays an important role in resistance agains t HSV-1 infection. Furthermore, nitric oxide (NO) may block the develo pment of Th1 cells via inhibition of IL-12 synthesis and thereby play a role in immune regulation.