Ectopic expression of DNA encoding IFN-alpha 1 in the cornea protects micefrom herpes simplex virus type 1-induced encephalitis

A novel approach to combat acute herpes simplex virus type I (HSV-1) infect ion has recently been developed by administration with a plasmid DNA constr uct encoding cytokine genes. Cytokines, especially type I IFNs (IFN-alpha a nd IFN-beta) play an important role in controlling acute HSV-1 infection. T he purpose of the present study mas to investigate the potential efficacy o f ectopically expressed IFN-alpha 1 against ocular HSV-1 infection followin g in situ transfection of mouse cornea with a naked IFN-alpha 1-containing plasmid DNA, Topical administration of the IFN-alpha 1 plasmid DNA exerted protection against ocular HSV-1 challenge in a time- and dose-dependent man ner and antagonized HSV-1 reactivation. In addition, IFN-alpha 1-transfecte d eyes expressed a fivefold increase in MHC class I mRNA over vector-treate d controls. The protective efficacy of the IFN-alpha 1 transgene antagonize d viral replication, as evidenced by the reduction of the viral gene transc ripts (infected cell polypeptide 27, thymidine kinase, and viral protein 16 ) and viral load in eyes and trigeminal ganglia during acute infection. The administration of neutralizing Ab to IFN-alpha beta antagonized the protec tive effect of the IFN-alpha 1 transgene in mice. Collectively, these findi ngs demonstrate the potential of using naked plasmid DNA transfection in th e eye to achieve ectopic gene expression of therapeutically active agents.