We have reported previously that ocular infection of different strains of mice with recombinant HSV-1 constitutively expressing IL-2 provokes CNS demyelination and optic neuropathy as determined by changes in visual-evoked cortical potentials and pathologic changes in the optic nerve and CNS, whereas recombinant viruses expressing IL-4, IFN-γ, IL-12p35, IL-12p40, or IL-12p70 do not induce this neuropathy. The goal of this study was to dissect the mechanism underlying the interplay between the immune system (elevation of IL-2) and an environmental factor (infection with HSV-1) that elicit this pathology. Similar results were obtained upon delivery of IL-2 into the mouse brain using osmotic mini-pumps or injection of mice with rIL-2 protein, IL-2 DNA, or IL-2 synthetic peptides prior to infection with wild-type (wt) HSV-1 strains McKrae and KOS. The critical role of IL-2 is further supported by our data indicating that a single mutation at position T27A in IL-2 completely blocks HSV-1-induced pathology. This study shows a novel model of autoimmunity in which viral infection and enhanced IL-2 causes CNS demyelination.
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