DA strain of Theiler's murine encephalomyelitis virus induces demyelination in nude mice

DA strain of Theiler's murine encephalomyelitis virus produces a chronic, progressive demyelinating disease in mice that resembles multiple sclerosis. An immunopathological mechanism for demyelination has been postulated, because there is a brisk immune response with low virus titers at the time of demyelination and because immunosuppression lessens the degree of demyelination. We inoculated Nude mice with DA virus to clarify the role of immune-mediated demyelination. Animals became paralyzed 3 weeks to 2 months after inoculation, usually dying within a week of appearance of signs. Demyelinated foci were present in the spinal cords, with evidence of degenerating myelin around intact axons as well as completely demyelinated, naked axons. Occasional macrophages were present, but none was seen actively stripping intact myelin lamellae. These results suggest that DA virus lytic infection, without a contribution from the T lymphocyte immune system, is sufficient to produce demyelination. It is likely that DA virus demyelination has varying mechanisms that may be active at different times.