Spinal cord and optic nerve demyelination in experimental herpes simplex virus type 2 infection

To produce a model of central nervous system (CNS) demyelination, three strains of herpes simplex virus type 2 (HSV-2) were injected intracerebrally into Swiss-Webster outbred mice. Animals developed pupillary abnormalities and leg weakness and, by light and electron microscopy, had focal lesions of primary demyelination in optic nerves and spinal cords. Oligodendrocytes and astrocytes in these lesions contained herpesvirus. Both mouse age and virus dose were important determinants of the rate and severity of the infectious process, as judged by mortality and clinical signs of disease. A low virus dose in older mice favored survival of neurologically abnormal mice beyond the acute stage of infection. When the MS, G, and 186 strains of HSV-2 were compared, no evidence of a major effect of virus strain on the clinical course or type of pathology was seen. This study demonstrates that HSV-2 can produce multifocal demyelination in the CNS in mice. The intracerebral route appears to be important in producing a model of more generalized demyelination unrelated to the site of injection than has been previously reported in other experimental herpesvirus infections. The possible relationship of this model to optic neuritis, neuromyelitis optica, and multiple sclerosis is discussed.