Central nervous system demyelination in Venezuelan equine encephalomyelitis infection. An experimental model of virus-induced myelin injury

Arboviruses are important pathogens for both animals and humans. Venezuelan equine encephalomyelitis virus (VEEV) is an arbovirus whose pathogenicity for grey matter structures has been previously studied. To our knowledge, the present study is the first to describe extensive inflammation and demyelination in spinal cord white matter of mice infected with VEEV. To probe a possible immunepathogenesis of white matter alterations in this infection, nude mice and heterozygous controls were similarly infected. Whereas controls still showed inflammatory demyelination, nude mice showed no white matter changes in the absence of a mononuclear inflammatory response. These results suggest that white matter changes in VEEV infection are dependent upon the host immune-response, rather than produced by primary viral cytolytic activity. Such findings are similar to those we and others obtained in a number of different viral infections and support the possibility that the host immune response may be the common denominator leading to myelin injury in a variety of viral diseases. The hypothesis of "by-stander killing" of myelin is discussed as a possible host-mediated mechanism of demyelination in viral infections.