title: Sequential infection of glial cells by the murine hepatitis virus JHM strain (MHV-4) leads to a characteristic distribution of demyelination.
abstract: An antigenic variant of the neurotropic murine coronavirus JHMV, designated 2.2-V-1, causes marked demyelination in the relative absence of encephalitis. It is thus useful for the study of the pathogenesis of demyelinating lesions. To better understand the sequential events leading to demyelination, we have examined murine brain and spinal cord tissue at daily intervals after intracerebral inoculation, evaluating them for the distribution of viral antigen, leukocyte infiltration, and demyelination. Immunohistochemical staining indicated that virus established primary infection in the ependymal cells in both brain and spinal cord before spreading into nearby structures and along white matter tracts by cell-to-cell contact. Spread from brain to spinal cord appeared to occur via cerebrospinal fluid. Viral replication was focally cytocidal for ependymal cells, and essentially noncytocidal for other neural cells including glia. In brain, viral antigen and inflammation reached a peak at day 5 postinfection, and rapidly subsided by day 10 postinfection. In spinal cord, viral antigen was less abundant than in brain and was maximal between days 7 and 9 postinfection. The inflammatory response and demyelination, however, were more severe persisting from day 7 through day 19. In the spinal cord, demyelinating lesions developed initially in areas closer to the central canal and were detected most prominently in the anterior funiculi. This finding suggests that the permissiveness of the ependymal cell is crucial to viral entry and that sequential infection of glial cells leads to the characteristic distribution of demyelination.
authors.affiliation: Department of Neurology, School of Medicine, University of Southern California, Los Angeles.
authors.forename: F I
authors.initials: FI
authors.lastname: Wang
authors.forename: D R
authors.initials: DR
authors.lastname: Hinton
authors.forename: W
authors.initials: W
authors.lastname: Gilmore
authors.forename: M D
authors.initials: MD
authors.lastname: Trousdale
authors.forename: J O
authors.initials: JO
authors.lastname: Fleming
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001921:Brain / Q000382:microbiology / Q000473:pathology; D003711:Demyelinating Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D006524:Hepatitis, Viral, Animal / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000276:immunology; D013116:Spinal Cord / Q000382:microbiology / Q000473:pathology
chemical_list: D000956:Antigens, Viral