April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Spike Gene Mediates Viral-Induced Experimental Optic Neuritis
Author Affiliations & Notes
  • K. S. Shindler
    Ophthalmology, Univ Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania
  • M. Dutt
    Ophthalmology, Univ Pennsylvania Scheie Eye Institute, Philadelphia, Pennsylvania
  • J. Das Sarma
    IISER-Kolkata, Kolkata, India
  • Footnotes
    Commercial Relationships  K.S. Shindler, None; M. Dutt, None; J. Das Sarma, None.
  • Footnotes
    Support  NIH grant EY015098, a Career Development Award from RPB, and the F. M. Kirby Foundation to KSS; FG1431-A-1 and RG3774A2-1 from the NMSS, and M.E.Groff Surg. Med. Res. and Ed. Charitable Trust to JDS
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 5349. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: neuro-ophthalmology: optic nerve • inflammation 

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