Resistance to ocular herpes simplex virus type 1 infection in IL-12 transgenic mice

Interleukin-12 (IL-12) is a potent inflammatory cytokine that influences the innate and adaptive immune response to microbial pathogens including viruses. It was reasoned that constitutive IL-12 production in mice would enhance resistance to herpes simplex virus type 1 (HSV-1) infection. To test this hypothesis, transgenic mice expressing the p35 and p40 genes of IL-12 under a glial fibrillary acidic protein (GFAP) promoter were ocularly infected with HSV-1. These mice displayed increased survival and reduced viral titers in the eye, trigeminal ganglion (TG), and brain stem in comparison to wild type controls. Consistent with these results, HSV-1 immediate early and early gene expression were reduced to 50-130-fold in the trigeminal ganglion of infected transgenic mice compared to infected, non-transgenic counterparts as determined by real time PCR. Associated with viral resistance, IL-12 and IFN-gamma mRNA levels and IL-12 protein were elevated in the eyes of the transgenic versus non-transgenic mice during the acute infection. Collectively, the data show the inherent resistance of mice constitutively expressing IL-12 to ocular HSV-1 infection-an outcome that is independent of the adaptive immune system at the time of infection.