Identification of nitric oxide synthase 2 as an innate resistance locus against ectromelia virus infection

To assess whether nitric oxide synthase 2 (NOS2) fulfills the criteria of an innate resistance locus against an acute viral infection, we inoculated genetically deficient NOS2-/- mice with virulent ectromelia virus (EV), the causative agent of mousepox. NOS2-/- mice proved highly susceptible to EV yet showed no diminution in other well-characterized anti-EV immune responses, i.e., gamma interferon secretion and NK cell and EV-specific cytotoxic T lymphocyte activities. Thus, the NOS2 locus can be considered a critical monogenic determinant of EV resistance that contributes to host survival.