Math Biology Seminar Abstracts

Wednesday October 24, 2001

3:05 pm JWB 208

Title:Viruses Can Silently Prime and Trigger Autoimmune Disease

Speaker: Robert S. Fujinami, PhD, Professor, Department of Neurology, University of Utah

Abstract: The etiology of multiple sclerosis (MS) is unknown. Factors contributing to its pathogenesis include genetics, age and environment. Twin studies found that if one twin developed MS, the other had a 30% chance of developing the disease. These data, as well as genotyping MS families, demonstrated that genetic factors contribute to MS. Migration studies have shown that age is also a risk factor for MS. Individuals moving from a high MS risk region to a low MS risk region after age 15 kept the high MS risk phenotype. In contrast, individuals migrating before age 15 acquired the MS risk of the region to which they moved. Environmental factors (infections) play a key role in the development of exacerbations. Several groups have demonstrated an association between viral infections and attacks of MS. Therefore, certain infections may trigger exacerbations.

Experimental allergic encephalomyelitis (EAE) is a widely used animal model for MS. We have used this model to explore the above factors in the development of autoimmune central nervous system (CNS) disease. Young female mice (prepubescent) were infected with recombinant viruses having molecular mimicry with self-CNS proteins. This represents viral infections occurring early in life. No clinical disease developed in these mice. However, when these mice were given a non-specific immunologic al challenge, mice developed inflammatory white matter lesions in the CNS. In other experiments mice were primed with a cDNA encoding a CNS antigen mirroring early infections. These mice were later challenged with a virus having no molecular mimicry. Some of these mice had white matter lesions. These data suggests that a non-specific viral infection could trigger an attack of autoimmune CNS disease in sub-clinically primed individuals. This study may help explain why no one virus has been identified as the cause of MS, but how infections can induce an exacerbation.

Supported by NMSS and NIH.

For more information contact J. Keener, 1-6089