Coronavirus infection and demyelination. Development of inflammatory lesions in Lewis rats.
Coronavirus infections of rodents can cause diseases of the central nervous system characterised by inflammatory demyelination. The lesions mimick in many aspects the pathology of multiple sclerosis in humans and of other neurological diseases. As an animal model for demyelination, we studied the MHV-JHM induced encephalomyelitis of Lewis rats. The pathomorphological analysis revealed patterns of lesions which developed in stages. Infected oligodendrocytes were first destroyed by necrosis. Later stages were characterized by demyelinated plaques. In the center of plaques, no virus antigen was found and oligodendrocytes were mainly destroyed by apoptosis. At the edge of plaques, virus antigen was expressed in parallel to infiltrations consisting of lymphocytes and macrophages. The prevailing mechanisms leading to demyelination may change individually and during defined stages of the disease. The transcriptional expression of chemoattractants and other mediators of inflammation was studied by semiquantitative RT-PCR. Virus induced inflammatory demyelination was accompanied by high expression of a relatively novel cytokine, the endothelial monocyte activating polypeptide II (EMAP II). By immunocytochemistry, EMAP II was detected in parenchymal microglia located both within the lesions and in unaffected areas. Furthermore, the level of transcriptional expression of the regulatory calcium binding S100 proteins MRP8, MRP14 and CP10 was associated with inflammatory demyelination and expression of IFN gamma, IL-2, TNF alpha, and iNOS.
Wege
H
H
Federal Research Centre for Virus Diseases of Animals, Friedrich-Loeffler-Institutes, Isle of Riems, Austria.
Schluesener
H
H
Meyermann
R
R
Barac-Latas
V
V
Suchanek
G
G
Lassmann
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D018352:Coronavirus Infections / Q000378:metabolism / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000473:pathology / Q000821:virology*; D015870:Gene Expression; D051379:Mice; D006517:Murine hepatitis virus / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic
D016207:Cytokines; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins; C077219:small inducible cytokine subfamily E, member 1; D019001:Nitric Oxide Synthase