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

The present study was undertaken to further characterize the anti-viral eff icacy of a plasmid DNA encoding IFN-alpha 1 against ocular herpes simplex v irus type 1 (HSV-1) infection. In mice ocularly treated with plasmid DNA en coding IFN-alpha 1, the efficacy of the transgene was inversely proportiona l 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 showe d efficacy against ocular HSV-1 infection compared with vaginal or intranas al delivery. Mice treated with the plasmid DNA encoding IFN-alpha 1 showed a significant reduction in viral Ag expression in the eyes and trigeminal g anglion that correlated with a reduction in immune cell infiltration into t he cornea and iris on days 3 and 6 postinfection, as evidenced by immunohis tochemical staining. Depleting mice of either CD4(+) or CD8(+) T lymphocyte s 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 transcrip t expression in the corneas 24 h post-treatment. Expression of the plasmid construct following topical application in the eye included the rectus musc les proximal to the cornea as well as the spleen. Collectively, the protect ive 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 lympho cytes early in the course of the infection, suggesting an indirect effect o f the transgene against HSV-l-induced mortality.