Neuronal and oligodendroglial infection by the WW strain of Theiler's virus

Abstract

Newborn ICR mice were infected by intracerebral inoculation of 10(5.3) LD50 of the WW strain of Theiler's virus and examined serially by virologic and ultrastructural methods. Maximal titers of 10(6) LD50 developed in the brain by day 8 when 90 per cent of the animals were dead or moribund. The virus first appeared and was most prominent in the thalamus, basal ganglia, and midbrain. It spread from these areas throughout the cortex, brainstem, and spinal cord but spared the cerebellar cortex. Both neurons and oligodendroglia were infected. Infected cells first showed dispersion of polyribosomes, accumulation of vesicles, and widening of perinuclear cisternae. Normal cytoplasmic organelles and the nucleus were displaced by an accumulation of viral crystals, membranous profiles, and fibrillar material. Within degenerating cells the nuclear chromatin became clumped and marginated and the cytoplasm was filled either with vesicles or masses of paracrystalline viral arrays. These changes were accompanied by a vigorous inflammatory response of lymphocytes, plasma cells, macrophages, neutrophils, and eosinophils. Lysis of oligodendroglia during acute infection with the WW strain of Theiler's virus may provide a stimulus for the late autoimmune demyelination that has been described in animals that survive the acute encephalitis.