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K. S. Shindler, M. Dutt, J. Das Sarma; Spike Gene Mediates Viral-Induced Experimental Optic Neuritis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5349.
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Infection of mice with neurovirulent strains of mouse hepatitis virus (MHV) is used as a model for virus-induced demyelination that mimics many pathologic features of multiple sclerosis. A significant incidence of optic neuritis occurs in mice infected with a demyelinating strain of MHV (MHV-A59), but not with the non-demyelinating strain, MHV-2. Mechanisms underlying this differential induction of optic neuritis are not known. We examined the potential role of spike, a glycoprotein involved in virus-host attachment, in mediating induction of optic neuritis.
Four week-old C57Bl/6 mice were inoculated intracranially with 50% LD50 dose of RSA59 strain (20,000 PFUs) or RSMHV2 (100 PFUs). RSA59 and RSMHV2 strains of MHV are isogenic (background is from demyelinating strain MHV-A59) except for the spike gene. Mice were sacrificed 5 and 30 days post-innoculation. 5 micron longitudinal sections of isolated optic nerves were assessed by H & E and immunohistochemistry for inflammatory cell markers. Axonal integrity was assessed by silver staining.
RSA59 induced optic neuritis, characterized by inflammatory cell infiltration of optic nerves, by day 5 post-innoculation, with significant loss of myelin and axonal damage detected at day 30, similar to effects of the parent virus MHV-A59 seen in prior studies. RSMHV2, however, induced little or no optic nerve inflammation with preserved myelin and retinal ganglion cell axons.
Results demonstrate that a neurovirulent spike gene is required for MHV strains to induce optic neuritis, as the spike gene from the non-demyelinating MHV2 strain rendered MHV-A59 incapable of inducing optic nerve inflammation, demyelination and axonal damage. The spike protein is a potential target for disrupting virus-host attachment that may have a role in treating optic neuritis and multiple sclerosis.
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