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H. Ghiasi, M. Zandian, R. Belisle, S. Nusinowitz, F. Hofman, K. Mott; A Recombinant HSV-1 Expressing Murine Interleukin-2 Induces Optic Neuritis in Different Strains of Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):828.
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IL-2 has been implicated in the pathology of multiple sclerosis (MS) through the clinical observation that MS patients have elevated levels of IL-2 in their CSF and sera. We sought to determine if, similar to MS, a recombinant HSV-1 constitutively expressing IL-2 can cause optic neuritis (ON) in ocularly infected mice.
Female BALB/c, C57BL/6, SJL/6, and 129SVE mice and male BALB/c mice were ocularly infected with recombinant HSV-IL-2 virus. Demyelination of optic nerves in infected mice was monitored histolologically using Luxol Fast Blue staining and by measurement of visual-evoked cortical potentials (VECPs). T cells and APCs depletion studies and knockout mice were examined for their ability to withstand optic nerve demyelination induced by HSV-IL-2.
Both focal and diffuse regions of demyelination of the optic nerves were found in the HSV-IL-12 infected mice as early as day 10 post infection and as late as 60 days post infection (the final experimental time point) in all strains of mice tested. Optic nerve demyelination was not observed in control mice ocularly infected with HSV-IFN-γ, HSV-IL-4, or wild-type HSV-1. Depletion and knockout mice studies suggest that CD8+ T cells are directly involved in the demyelination process, while macrophages playing a protective role against CNS demyelination. VECP responses were delayed significantly in the HSV-IL-2 infected mice as compared with mice infected with control viruses.
Our results demonstrate for the first time that a combination of viral infection and constitutive expression of IL-2, but not IFN-γ or IL-4, can result in demyelination in the optic nerves of ocularly infected mice.
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