Uncoupled relationship between demyelination and primary infection of myelinating cells in Theiler's virus encephalomyelitis

Theiler's virus infection in mice produces a chronic demyelinating disease which appears to be based on an immune pathogenesis rather than on direct viral destruction of myelin-supporting cells. The purpose of the present study is to ascertain whether viral antigen is present in the cytoplasm of such cells in areas of demyelination. Because of the difficulty of identifying oligodendrocytes in tissues rich in infiltrating mononuclear cells and fixed for immunohistochemistry, I turned to a recently described form of Theiler's virus encephalomyelitis which follows inoculation with the attenuated ww strain and is characterized by extensive spinal cord remyelination by invading Schwann cells and by recurrent demyelination of Schwann cell-remyelinated axons. The unlabeled antibody peroxidase-antiperoxidase technique was employed to study whether such spinal cord Schwann cells were primarily infected by virus at the time when recurrent demyelination was occurring. Whereas other types of cells, including neurons, astrocytes, and macrophages, contained abundant viral antigen, no positive immune reaction was observed in Schwann cells. These results correlate with our previous studies which had suggested that demyelination in this viral model is not dependent on primary viral attack on myelinating cells but is probably dependent on the host immune response.