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

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.

The Role of Granulocyte-Macrophage Colony-Stimulating Factor in Murine Models of Multiple Sclerosis

“…GM-CSF-deficient C3HeB/FeJ mice develop EAE because IL-17 is able to compensate for the loss of GM-CSF, and is able to promote neutrophil accumulation, inflammation, and demyelination [67]. Interestingly, this study also determined that the co-expression of IL-17 and GM-CSF is required to promote immune cell migration into the brain, which is normally inhibited by IFNγ [79]. This suggests that, while GM-CSF may be important for promoting EAE pathology, it is not the only cytokine that is essential.…”

“…One model that may depend on GM-CSF signaling is the Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) [77]. Theiler's murine virus is an enteric commensal in most mouse stains; however, when injected via intracranial injection into susceptible mice, such as SJL/J mice, the result is a chronic and progressive demyelinating disease [78,79]. The chronic phase of TMEV-IDD is characterized by inflammation, demyelination, axonal degeneration, and astrogliosis, making this a suitable model to study MS progression [79].…”

“…Theiler's murine virus is an enteric commensal in most mouse stains; however, when injected via intracranial injection into susceptible mice, such as SJL/J mice, the result is a chronic and progressive demyelinating disease [78,79]. The chronic phase of TMEV-IDD is characterized by inflammation, demyelination, axonal degeneration, and astrogliosis, making this a suitable model to study MS progression [79]. One study suggested that GM-CSF may play a role in promoting pathology in this model.…”

Acute Disseminated Encephalomyelitis with Seizures and Myocarditis: A Fatal Triad

“…Furthermore, two potentially causative agents were detected: human metapneumovirus, which can be associated with encephalitis, focal seizures, and status epilepticus [15], and rhinovirus, a respiratory pathogen and member of the Picornaviridae family. In mice, but not humans, a virus of the same family (Theiler's murine encephalomyelitis virus, TMEV) not just induces encephalomyelitis, but also cardiac lesions [16]. This virus triggers innate immunity as well as antiviral immune responses and autoimmune-induced myocardial damage [16].…”

“…In mice, but not humans, a virus of the same family (Theiler's murine encephalomyelitis virus, TMEV) not just induces encephalomyelitis, but also cardiac lesions [16]. This virus triggers innate immunity as well as antiviral immune responses and autoimmune-induced myocardial damage [16]. We would, however, be hesitant to claim a definite link between rhinovirus and myocarditis because of the extraordinary rarity of this association [17,18].…”