Topical application of the cornea post-infection with plasmid DNA encoding interferon- alpha 1 but not recombinant interferon- alpha A reduces herpes simplex virus type 1-induced mortality in mice

A study was undertaken to compare the efficacy of recombinant interferon (rIFN)- alpha A to plasmid DNA encoding IFN- alpha 1 against ocular herpes simplex virus type 1 (HSV-1) infection. The topical application of rIFN- alpha A (100-300 units/eye) onto the cornea of mice subsequently infected 24 h later with HSV-1 antagonized viral-induced mortality. The enhancement in cumulative survival in the rIFN- alpha A-treated mice correlated with a reduction of viral titers recovered in the eye and trigeminal ganglion (TG) at 3 and 6 days post-infection. The protective effect was site-specific such that when rIFN- alpha A was administered orally or intranasally, no efficacy against HSV-1 was observed. However, the protective effect was time-dependent. Specifically, when the rIFN- alpha A (100-1000 units /eye) was administered at 24 h post-infection, no protective effect was observed against HSV-1 compared to the vehicle-treated group. In contrast, plasmid DNA (100 mu g/eye) containing the IFN- alpha 1 transgene showed significant protection when topically applied 24 h post-infection. Although the transgene was found to traffic distal from the site of application (eye), including the trigeminal ganglion and the spleen where CD11b super(+) and CD11c super(+) cells express the transgene, the migration of the transgene did not correlate with efficacy. Collectively, the results suggest that naked DNA encoding type I IFN applied post-infection provides a greater degree of protection against ocular HSV-1 infection in comparison with recombinant protein effectively antagonizing viral replication and spread.