title: Transgenic expression of viral capsid proteins predisposes to axonal injury in a murine model of multiple sclerosis.
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 (>10µm(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.
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Mn. 55905, USA.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Denic
authors.forename: Laurie
authors.initials: L
authors.lastname: Zoecklein
authors.forename: Jason
authors.initials: J
authors.lastname: Kerkvliet
authors.forename: Louisa
authors.initials: L
authors.lastname: Papke
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Edukulla
authors.forename: Arthur
authors.initials: A
authors.lastname: Warrington
authors.forename: Allan
authors.initials: A
authors.lastname: Bieber
authors.forename: Larry R
authors.initials: LR
authors.lastname: Pease
authors.forename: Chella S
authors.initials: CS
authors.lastname: David
authors.forename: Moses
authors.initials: M
authors.lastname: Rodriguez
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000473:pathology* / Q000821:virology; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004660:Encephalitis / Q000209:etiology / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009103:Multiple Sclerosis / Q000150:complications / Q000473:pathology / Q000821:virology; D010455:Peptides / Q000378:metabolism; D045442:Rotarod Performance Test / Q000379:methods; D017945:Theilovirus / Q000235:genetics / Q000472:pathogenicity; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D036022:Capsid Proteins; D010455:Peptides; D014764:Viral Proteins