Abstract
Theiler’s murine encephalomyelitis virus (TMEV), a naturally occurring, enteric pathogen of mice is a Cardiovirus of the Picornaviridae family. Low neurovirulent TMEV strains such as BeAn cause a severe demyelinating disease in susceptible SJL mice following intracerebral infection. Furthermore, TMEV infections of C57BL/6 mice cause acute polioencephalitis initiating a process of epileptogenesis that results in spontaneous recurrent epileptic seizures in approximately 50% of affected mice. Moreover, C3H mice develop cardiac lesions after an intraperitoneal high-dose application of TMEV. Consequently, TMEV-induced diseases are widely used as animal models for multiple sclerosis, epilepsy, and myocarditis. The present review summarizes morphological lesions and pathogenic mechanisms triggered by TMEV with a special focus on the development of hippocampal degeneration and seizures in C57BL/6 mice as well as demyelination in the spinal cord in SJL mice. Furthermore, a detailed description of innate and adaptive immune responses is given. TMEV studies provide novel insights into the complexity of organ- and mouse strain-specific immunopathology and help to identify factors critical for virus persistence.
Highlights
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 present review summarizes morphological lesions and pathogenic mechanisms triggered by TMEV with a special focus on the development of hippocampal degeneration and seizures in C57BL/6 mice as well as demyelination in the spinal cord in SJL mice
The results show that Treg represents a double-edged sword in TMEV-IDD susceptible mice with opposing effects depending on the disease phase
Summary
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 course of Theiler’s murine encephalitis (TME) depends on the virus and mouse strains as well as other factors including intestinal microbiota and stress [3,14,15,16,17]. Mice develop an acute polioencephalomyelitis within two weeks following experimental intracerebral TMEV infection. The genetic background of mice in addition to the virus strain has an important impact on the disease course, especially on the development of chronic demyelination (Figure 1). Translation of the polyprotein is regulated by an internal ribosomal entry site (IRES). This polyprotein is cleaved into 12 proteins including L, Viral proteins 1–4 (VP1–4), 2A–C, and 3A–D [29,30]. While cellular microRNAs seem to have no significant impact on TMEV replication, an enhancer-like lncRNA, termed NeST which interacts with the murine viral susceptibility locus Tmevp and thereby controls IFNγ expression, is involved in TMEV persistence and may serve as a potential target for novel antiviral drugs [35,36]
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