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

Purpose. Type I interferons (IFN-alpha and -beta) are an innate immune comp onent 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-alpha 1 onto mouse corneas prior to ocular HSV- 1 infection provided prophylactic efficacy against HSV-1-induced encephalit is. As a result, the present study was undertaken to investigate the kineti cs of the efficacy mediated by the IFN-alpha 1 transgene following ocular c hallenge with HSV-1. Method. Mice were ocularly infected with a lethal dose of HSV-1 (450 plaque forming units/eye, McKrae strain) following corneal scarification and topi cally administered the pCMV-IFN-alpha 1 transgene or pCMV-beta (plasmid vec tor) starting at 12, 24, or 48 hr post infection. Cumulative survival of in fected 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-IFN alpha 1 transgene survived to a gre ater degree compared to mice topically administered the plasmid vector alon e in a time-dependent manner. The protective effect correlated with a decre ase in the viral load and expression of HSV-1 immediate early and early gen e transcripts, infected cell protein-27 and thymidine kinase respectively i n the trigeminal ganglion 6 days post infection. Conclusion. These results suggest that the application of plasmid DNA encod ing IFN-alpha 1 transgene is beneficial as a therapeutic approach when appl ied early after HSV-1 infection of the corneas.