Viral models of multiple sclerosis: neurodegeneration and demyelination in mice infected with Theiler's virus

Multiple sclerosis (MS) is a complex inflammatory disease of unknown etiology that affects the central nervous system (CNS) white matter, and for which no effective cure exists. Indeed, whether the primary event in MS pathology affects myelin or axons of the CNS remains unclear. Animal models are necessary to identify the immunopathological mechanisms involved in MS and to develop novel therapeutic and reparative approaches. Specifically, viral models of chronic demyelination and axonal damage have been used to study the contribution of viruses in human MS, and they have led to important breakthroughs in our understanding of MS pathology. The Theiler's murine encephalomyelitis virus (TMEV) model is one of the most commonly used MS models, although other viral models are also used, including neurotropic strains of mouse hepatitis virus (MHV) that induce chronic inflammatory demyelination with similar histological features to those observed in MS. This review will discuss the immunopathological mechanisms involved in TMEV-induced demyelinating disease (TMEV-IDD). The TMEV model reproduces a chronic progressive disease due to the persistence of the virus for the entire lifespan in susceptible mice. The evolution and significance of the axonal damage and neuroinflammation, the importance of epitope spread from viral to myelin epitopes, the presence of abortive remyelination and the existence of a brain pathology in addition to the classical spinal cord demyelination, are some of the findings that will be discussed in the context of this TMEV-IDD model. Despite their limitations, viral models remain an important tool to study the etiology of MS, and to understand the clinical and pathological variability associated with this disease.