*4.3.2 Murine hepatitis virus (MHV)*

Like TMEV, MHV is a natural pathogenic agent of mice that infects all types of CNS cells (neurons, astrocytes, and …). Specific strains of MHV, such as John Howard Mueller (JHM), have a distinctive tropism of CNS leading to severe acute encephalitis [74]. Strains with a less pronounced neurotropism, such as the gliatropic MHV-A59 strain, generally establish a persistent CNS infection, contributing to chronic inflammation and demyelination. Mice inoculated intra-nasally or intra-cerebrally with the JHM virus or MHV-A59 strains mount a robust immune response leading to an influx of immune cells that largely clear the virus, although low-level viral infection persists in animals surviving from the acute infection [75]. In contrast to TMEV, infected MHV-susceptible mice develop a single major symptomatic episode such as hind limb laziness, ataxia, and paralysis, most of which recover. Demyelination begins about a week after infection, with the peak at week 3–4, after which lesion repair and remyelination can occur [76].

## *4.3.3 Semliki Forest virus (SFV)*

SFV is a neurotropic alphavirus of the family Togaviridae that infects neural cells in the CNS such as neurons and oligodendrocytes. In adult C57BL/6 and BALB/c mice, the virus is largely cleared from the CNS by 6 days post-infection. Demyelination peaks around day 14 and subsequently wanes, with sporadic and mild clinical symptoms [77]. The CNS demyelination observed in SFV-infected mice appears to involve T cells, as demyelination does not occur in nude or SCID

### *Experimental* in Vitro *and* in Vivo *Models of Demyelinating Disorders DOI: http://dx.doi.org/10.5772/intechopen.100163*

mice. Indeed, in BALB/c mice, depletion of CD8+ but not CD4+ T cells abolishes demyelinating lesions. Demyelination may also occur following cytolytic damage of virus-infected oligodendrocytes. In this model, in C57BL/6 mice, molecular mimicry may also take on a role in demyelination, as infected mice exhibit proliferative T cell responses to myelin basic protein (MBP), and antibodies (Abs) reactive to MBP and myelin oligodendrocyte glycoprotein (MOG). Indeed, it was suggested that demyelinating lesions are mainly made by antibody responses, which have cross reaction to MOG and the SFV E2 protein [78].
