Therapeutic efficacy of DNA encoding IFN-a1 against corneal HSV-1 infection

Abstract

Purpose. Type I interferons (IFN-a and -ß) are an innate immune component that plays a critical role in controlling herpes simplex virus type 1 (HSV-1) infection. We have previously shown that topical administration of a plasmid DNA encoding IFN-a1 onto mouse corneas prior to ocular HSV-1 infection provided prophylactic efficacy against HSV-1-induced encephalitis. As a result, the present study was undertaken to investigate the kinetics of the efficacy mediated by the IFN-a1 transgene following ocular challenge with HSV-1. Methods. Mice were ocularly infected with a lethal dose of HSV-1 (450 plaque forming units/eye, McKrae strain) following corneal scarification and topically administered the pCMV-IFN-a1 transgene or pCMV-ß (plasmid vector) starting at 12, 24, or 48 hr post infection. Cumulative survival of infected mice was recorded. In addition, the effect of the transgene on viral replication and viral gene expression was determined from tissues 3 and 6 days post infection by plaque assay and RT-PCR respectively. Results. Mice treated with the pCMV-IFNa1 transgene survived to a greater degree compared to mice topically administered the plasmid vector alone in a time-dependent manner. The protective effect correlated with a decrease in the viral load and expression of HSV-1 immediate early and early gene transcripts, infected cell protein–27 and thymidine kinase respectively in the trigeminal ganglion 6 days post infection. Conclusion. These results suggest that the application of plasmid DNA encoding IFN-a1 transgene is beneficial as a therapeutic approach when applied early after HSV-1 infection of the corneas.