Plasmid DNA encoding IFN-alpha 1 antagonizes herpes simplex virus type 1 ocular infection through CD4+ and CD8+ T...

The present study was undertaken to further characterize the anti-viral efficacy of a plasmid DNA encoding IFN-alpha1 against ocular herpes simplex virus type 1 (HSV-1) infection. In mice ocularly treated with plasmid DNA encoding IFN-alpha 1, the efficacy of the transgene was inversely proportional to the amount of virus used to infect the mice. Ocular treatment of mice with the IFN-alpha 1 transgene was the only mucosal route tested that showed efficacy against ocular HSV-1 infection compared with vaginal or intranasal delivery. Mice treated with the plasmid DNA encoding IFN-alpha 1 showed a significant reduction in viral Ag expression in the eyes and trigeminal ganglion that correlated with a reduction in immune cell infiltration into the cornea and iris on days 3 and 6 postinfection, as evidenced by immunohistochemical staining. Depleting mice of either CD4+ or CD8+ T lymphocytes completely blocked the resistance to herpes simplex virus type 1-induced mortality in mice treated with the IFN-alpha 1 transgene. In the absence of infection, the application of naked DNA encoding IFN-alpha 1 significantly increased the levels of IL-6- and IFN-gamma-inducible protein 10 transcript expression in the corneas 24 h post-treatment. Expression of the plasmid construct following topical application in the eye included the rectus muscles proximal to the cornea as well as the spleen. Collectively, the protective efficacy of the IFN-alpha 1 transgene against ocular HSV-1 infection is dependent upon the local or distal participation of CD4+ and CD8+ T lymphocytes early in the course of the infection, suggesting an indirect effect of the transgene against HSV-1-induced mortality.