Analysis of murine hepatitis virus (JHM strain) tropism toward Lewis rat glial cells in vitro. Type I astrocytes and brain macrophages (microglia) as primary glial cell targets.
The murine hepatitis virus, JHM strain, causes a relapsing subacute demyelinating encephalomyelitis in Lewis rats after intracranial infection. The disease process involves both virus persistence within glial cells and the induction of autoimmunological attack of myelin, however, the relative importance of these features involved in chronic relapsing demyelination remains to be determined. In this report, we analyze the tropism of JHM virus to various neural cell types present within primary Lewis rat central nervous system cultures. Infection of primary cultures with JHM virus revealed that type I astrocytes and brain macrophages are the initial target cells of infection and that the myelin-forming oligodendrocytes are comparatively resistant, becoming infected only rarely through virus mediated cell fusion with previously infected cells. In addition, infection of cultures after removal of oligodendrocytes by various means had no effect on the tropism of JHM virus for the cultures. Cytopathic effects of JHM virus proceed rapidly by cell fusion within the astrocyte-macrophage monolayer, leaving the oligodendrocyte population largely unaffected. Therefore, the highly selective infection of type I astrocytes and macrophages appears to form the basis of JHM virus neurotropism in Lewis rats. These results indicate that JHM virus infection of astrocytes and brain macrophages may be more important in inducing chronic relapsing demyelinating processes than direct infection of the myelin-forming oligodendrocytes. Other possible pathways leading to chronic demyelination in rats involving type I astrocytes and brain macrophages are discussed.
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D002478:Cells, Cultured; D003332:Coronaviridae / Q000472:pathogenicity; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006520:Hepatitis, Animal / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D009457:Neuroglia / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew