Andreas Zurbriggen

Is Theiler's murine encephalomyelitis virus infection of mice an autoimmune disease?

Viruses can initiate disease by many different means. Direct viral, immune mediated and host factors all play important parts. Molecular mimicry or having cross‐reacting determinants that result in immune responses which have the potential to cause damage can be incorporated into this framework. Here, autoimmune responses generated by virus infection have been presented in relation to these other parameters. The cross‐reacting immune response originally generated by virus would have to be directed toward or involve a disease inducing site such as an EAE (encephalitogenic), thyroiditis, or diabetogenic site. If the cross‐reaction took place at a nondisease inducing site, the ensuring immune response may result in the production of autoantibodies, however no disease would occur. In other systems autoantibodies can potentiate an ongoing inflammatory response. This may be the case that is described here with Theilers murine encephalomyelitis virus infection. Lastly, viruses having common determinants with MHC determinants may modify immune responses leading to immunosuppression and allowing virus to persist. In addition, similar determinants may lead to disease by an alternative route. For example, we have described a region of human cytomegalovirus that has a common determinant with HLA DR beta chain. This region is associated with diabetes in humans (Todd et al. 1988). Thus, many factors are involved in the outcome of disease induction by viruses of which autoimmunity is one.

Monoclonal antibody defines determinant between Theiler's virus and lipid-like structures ☆

Theilers murine encephalomyelitis virus is known to cause a chronic demyelinating disease in mice. The contributions of immunologic factors, i.e. humoral and cellular responses to virus and/or myelin components, and direct virus-cell interactions leading to demyelination are still unclear. One important factor could be antibody initiation of myelin destruction. Here we describe four monoclonal antibodies that react with Theilers murine encephalomyelitis virus. Three of these neutralize the virus and one of these three could also bind to various lipid-like structures including galactocerebroside, a myelin component. Further, this monoclonal antibody reacted with oligodendrocyte-like cells in vitro. All four monoclonal antibodies reacted with VP-1 by Western blot analysis. Thus, an immune response generated by virus that cross-reacts with a myelin element such as galactocerebroside could play a role in directing autoimmune processes toward myelin destruction.

Pathogenesis of Theiler's murine encephalomyelitis virus

Publisher Summary Theilers murine encephalomyelitis virus belongs to the family of picornaviridae. Picornaviruses are small ( “pico”), phylogenetically related RNA viruses. Based on different biochemical and biophysical characteristics picornaviruses are subdivided into four groups: enteroaphthovirus (foot-and-mouth disease virus), cardiovirus [encephalomyocarditis virus (EMCV), Mengo virus], and rhinovirus (human rhinovirus). Theilers murine encephalomyelitis virus was originally classified among the picornaviridae as an enterovirus because of its biological similarities with poliovirus. Further comparison of the complete genome of TMEV BeAn 8386 strain identifies remarkable similarities at the level of nucleotides and predicted amino acids between BeAn and the cardioviruses EMCV and Mengo virus. Theilers murine encephalomyelitis virus is a single-stranded nonenveloped RNA virus. The viral RNA is of positive sense, having the same polarity as mRNA. Viral mRNA lacks the cap structure found at the 5’ end of almost all eukaryotic mRNAs.