Transgenic expression of viral capsid proteins predisposes to axonal injury in a murine model of multiple sclerosis

Aleksandar Denic, Laurie Zoecklein, Jason Kerkvliet, Louisa Papke, Ramakrishna Edukulla, Arthur Warrington, Allan Bieber, Larry R. Pease, Chella S. David, Moses Rodriguez

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

We used transgenic expression of capsid antigens to Theiler's murine encephalomyelitis virus (TMEV) to study the influence of VP1, VP2 or VP2 121-130 to either protection or pathogenesis to chronic spinal cord demyelination, axonal loss and functional deficits during the acute and chronic phases of infection. We used both mice that are normally susceptible (FVB) and mice normally resistant (FVB.D b) to demyelination. Transgenic expression of VP2 121-130 epitope in resistant FVB.D b mice caused spinal cord pathology and virus persistence because the VP2 121-130 epitope is the dominant peptide recognized by D b, which is critical for virus clearance. In contrast, all three FVB TMEV transgenic mice showed more demyelination, inflammation and axonal loss as compared with wild-type FVB mice, even though virus load was not increased. Motor function measured by rotarod showed weak correlation with total number of midthoracic axons, but a strong correlation with large-caliber axons (>10 μm 2). This study supports the hypothesis that expression of viral capsid proteins as self influences the extent of axonal pathology following Theiler's virus-induced demyelination. The findings provide insight into the role of axonal injury in the development of functional deficits that may have relevance to human demyelinating disease.

Original languageEnglish (US)
Pages (from-to)501-515
Number of pages15
JournalBrain Pathology
Volume21
Issue number5
DOIs
StatePublished - Sep 1 2011

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Keywords

  • Theiler's murine encephalomyelitis virus (TMEV)
  • axonal loss
  • capsid antigens
  • demyelination

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

Cite this

Denic, A., Zoecklein, L., Kerkvliet, J., Papke, L., Edukulla, R., Warrington, A., Bieber, A., Pease, L. R., David, C. S., & Rodriguez, M. (2011). Transgenic expression of viral capsid proteins predisposes to axonal injury in a murine model of multiple sclerosis. Brain Pathology, 21(5), 501-515. https://doi.org/10.1111/j.1750-3639.2011.00474.x