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1 in the Cornea Protects Mice from Herpes Simplex Virus Type 1-Induced Encephalitis1
*
Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans, LA 70112; and
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037
A novel approach to combat acute herpes simplex virus type 1
(HSV-1) infection has recently been developed by administration with a
plasmid DNA construct encoding cytokine genes. Cytokines, especially
type I IFNs (IFN-
and IFN-ß) play an important role in controlling
acute HSV-1 infection. The purpose of the present study was to
investigate the potential efficacy of ectopically expressed IFN-1
against ocular HSV-1 infection following in situ transfection of mouse
cornea with a naked IFN-1-containing plasmid DNA. Topical
administration of the IFN-1 plasmid DNA exerted protection against
ocular HSV-1 challenge in a time- and dose-dependent manner and
antagonized HSV-1 reactivation. In addition, IFN-1-transfected eyes
expressed a fivefold increase in MHC class I mRNA over vector-treated
controls. The protective efficacy of the IFN-1 transgene antagonized
viral replication, as evidenced by the reduction of the viral gene
transcripts (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-ß
antagonized the protective effect of the IFN-1 transgene in mice.
Collectively, these findings demonstrate the potential of using naked
plasmid DNA transfection in the eye to achieve ectopic gene expression
of therapeutically active agents.
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