Viral induced demyelination

Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex ce ll-cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no in fectious virus is readily evident, virus reactivation and viral-induced tis sue damage. These studies have also provided excellent paradigms to study t he interactions between the immune system and the central nervous system (C NS). Although of interest in their own right, an understanding of the diver se mechanisms used by viruses to induce demyelination may shed light into t he etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a vira l infection acquired during adolescence might initiate MS after a long peri od of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non-enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary r esult of axonal loss, in many examples of viral induced demyelination, myel in loss is primary and associated with axonal sparing. This suggests that d emyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal ce llular homeostasis and subsequent oligodendroglial death; 3) a vigorous vir us-specific inflammatory response wherein the virus replicates in a cell ty pe other than oligodendroglia, but cytokines and other immune mediators dir ectly damage the oligodendroglia or the myelin sheath; or 4) infection init iates activation of an immune response specific for either oligodendroglia or myelin components. Virus-induced inflammation may be associated with the processing of myelin or oligodendroglial components and their presentation to the host's own T cell compartment. Alternatively, antigenic epitopes de rived from the viral proteins may exhibit sufficient homology to host compo nents that the immune response to the virus activates autoreactive T cells, i.e. molecular mimicry. Although it is not clear that each of these potent ial mechanisms participates in the pathogenesis of human demyelinating dise ase, analysis of the diverse demyelinating viral infections of both humans and rodents provides examples of many of these potential mechanisms.