Mechanism of demyelination in JHM virus encephalomyelitis

Abstract

Weanling mice were given intraperitoneal inoculations of the neurotropic, JHM strain of mouse hepatitis virus, the virulence of which had been altered by repeated mouse passages. Five to seven days later many animals developed hind leg paralysis. The pathology consisted of an acute encephalomyelitis with patchy demyclinating lesions in the brain stem and spinal cord. Virus particles, consistent with the appearance of corona viruses, were found in the cytoplasm of cells that were identified as oligondendrocytes by demonstrating connections of their plasma membranes with myelin lamellae. Following the degeneration of oligodendrocytes the myelin sheaths disintegrated or were stripped off intact axons by cytoplasmic tongues of polymorpho-and mononuclear leucocytes that intruded between myelin lamellae. The findings indicate that JHM virus has an affinity for oligodendroeytes in weanling mice and that demyelination occurs subsequently to the degeneration of the infected oligodendrocytes.

Mechanisms of Immunopathology in Murine Models of Central Nervous System Demyelinating Disease

“…MHV infects and replicates within oligodendrocytes, the myelin-synthesizing cells of the CNS (61,62), and it can be argued that oligodendrocyte damage or death is the major mechanism of demyelination (63,64). However, mice exposed to immunosuppressive doses of irradiation following JHM strain of mouse hepatitis virus infection showed little demyelination despite the presence of virus in oligodendrocytes and reconstituting irradiated mice with splenocytes from unirradiated-infected mice restored demyelination (65).…”

Host Genetic Control of Mouse Hepatitis Virus Type 4 (JHM Strain) Replication. I. Restriction of Virus Amplification and Spread in Macrophages from Resistant Mice

“…Mouse hepatitis virus type 4 (MHV-4, JHM strain), a member of the coronavirus family, is attracting increasing interest as an agent of both virus-induced encephalomyelitis and virusinduced demyelination (Bailey et al, 1949;Waksman & Adams, 1962;Lampert et al, 1973 ;Weiner, 1973;ter Meulen et al, 1981 ;Knobler et al, 1981Knobler et al, , 1982. Resistance to MHV-4-induced fatal central nervous system disease is inherited as a single autosomal recessive trait, independent of the major histocompatibility complex, expressed at the level of the neuronal cell (Knobler et al, 1981).…”

Genetic Variation of Neurotropic and Non-neurotropic Murine Coronaviruses

“…The original isolates of murine coronaviruses were recovered from different mouse strains and, so far, animal experiments to test the organ tropism of these viruses and to study the pathogenic mechanisms by which these strains induce diseases have mainly been carried out in mice (Lampert et al, 1973;Weiner, 1973). Recently, however, it has been shown in weanling rats that the murine coronavirus JHM induces different types of central nervous system (CNS) disease which can be accompanied by marked demyelination (Nagashima et al, 1978(Nagashima et al, a, b, 1979.…”