Three immune‐mediated disease models induced by Theiler's virus: Multiple sclerosis, seizures and myocarditis

Abstract

Theiler’s murine encephalomyelitis virus (TMEV) infection has been used as a viral model for multiple sclerosis (MS), as TMEV can induce chronic inflammatory demyelinating lesions with viral persistence in the spinal cord of SJL/J mice. In contrast, when C57BL/6 mice are infected with TMEV, the mice can clear the virus from the central nervous system (CNS), without viral persistence or demyelination, but develop seizures and hippocampal sclerosis, which has been used as a viral model for seizures/epilepsy. In the two TMEV-induced CNS disease models, not only viral infection, but also immune responses contribute to the pathogenesis. Interestingly, acquired immunity plays an effector role in the MS model, whereas innate immunity appears to contribute to the development of seizures. Recently, we have established the third TMEV-induced disease model, a mouse model for viral myocarditis, using C3H mice. TMEV-induced myocarditis is a triphasic disease, which mimics human myocarditis; phase I, mediated by viral replication in the heart and innate immunity; phase II, mediated by acquired immunity; and phase III, resulted from cardiac fibrosis. The genetic susceptibility to the aforementioned three models (MS, seizures and myocarditis) differs among mouse strains. We have compared and contrasted the three models induced by one single pathogen, TMEV, particularly in regard to the roles of T helper cells and natural killer T cells, which will give an insight into how interactions between the immune system and the host’s genetic background determine the tissue tropism of virus and the development of virus-induced organ-specific immunopathology.

Facets of Theiler’s Murine Encephalomyelitis Virus-Induced Diseases: An Update

“…Theiler’s murine encephalomyelitis virus (TMEV)-induced diseases are used as models for multiple sclerosis (MS), virus-induced seizures/epilepsy, and virus-induced myocarditis [1,2,3,4,5,6,7,8,9]. The virus belongs to the genus Cardiovirus of the Picornaviridae family, which also includes Vilyuisk human encephalomyelitis virus (VHEV), Theiler’s-like virus of rats, Saffold virus, and Saffold virus 2 [10].…”

Acute Disseminated Encephalomyelitis with Seizures and Myocarditis: A Fatal Triad

“…Nevertheless, this raises the question if certain viruses can induce similar injury to the brain and heart in humans, too. Different viruses were found to be associated with either multiple sclerosis, myocarditis, or epilepsy [4]. Extended diagnostics were performed on blood, serum, postmortem lung, brain, and heart tissues, but neither pathogens nor antibodies or evidence for paraneoplastic cause could be found (Table S1).…”

“…Cardiac complications have only been rarely reported [2,3]. Myocarditis has not yet been described in humans but is known to coexist with ADEM and seizures in the Theiler mouse model of a demyelinating disease [4]. Here, we report the first human case of this triad.…”

Severe and multifaceted systemic immunosuppression caused by experimental cancers of the central nervous system requires release of non-steroid soluble mediators

“…C57BL/6 mice clear TMEV infection within 21-45 days post infection (15,16,20,48). Because C57BL/6 mice mount an effective antiviral CD8 T cell response, this model allows us to determine whether thymic involution is reversible upon viral clearance (20,74). Thymic involution was not detectible in mice 30 days post TMEV infection and was only observed acutely (Figure 7 K).…”