Format

Send to

Choose Destination
See comment in PubMed Commons below
Brain Pathol. 2011 Sep;21(5):501-15. doi: 10.1111/j.1750-3639.2011.00474.x. Epub 2011 Feb 11.

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

Author information

1
Department of Neurology, Mayo Clinic, Rochester, Mn. 55905, USA.

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.

PMID:
21314744
PMCID:
PMC3139028
DOI:
10.1111/j.1750-3639.2011.00474.x
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center