Role of the immune response in Sindbis virus-induced paralysis of SJL/J mice.
The pathologic role of the specific immune and inflammatory responses to viral infections of the CNS was investigated by using mice which are susceptible (SJL/J) and resistant (C57Bl6 and BALB/c) to the development of experimental autoimmune encephalomyelitis (EAE). Intracerebral inoculation of 10(4) PFU of Sindbis virus (SV) into 6- to 8-wk-old SJL/J mice resulted in a severe and sometimes fatal encephalomyelitis. A mild to severe hind leg paralysis was observed around days 6 to 7 postinfection (pi) which closely resembled EAE stages and persisted for up to 8 wk pi. Immunosuppression with cyclophosphamide on day 4 alleviated the severity of this disease. Significant perivascular and parenchymal infiltration was present in the brains and spinal cords of SV-infected SJL/J mice for up to 1 mo. This apparent immunopathologic reaction was found to be a characteristic of SJL/J mice, because infection of 6- to 8-wk-old BALB/c and C57Bl6 mice with SV did not cause paralytic disease. These mice also exhibited a significantly milder cellular infiltrate which was mostly resolved on day 12 to 14 pi. Titers of virus in the brain and spinal cords of mice were comparable with clearance by day 7 pi. SV-specific lymphoproliferation and serum antibody responses were also comparable in all mice. SV-infected SJL/J mice developed antibodies to myelin components as demonstrated in Western blots and responded to myelin basic protein by lymphoproliferation. Lymph node cells from these mice, after in vitro challenge with myelin basic protein, transferred a mild EAE-like disease to naive recipients and potentiated subclinical EAE into a severe disease.
Mokhtarian
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Department of Medicine, Maimonides Medical Center, Brooklyn, NY 11219.
Grob
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Griffin
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D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology; D005260:Female; D007116:Immunization, Passive; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D010243:Paralysis / Q000209:etiology / Q000276:immunology*; D012845:Sindbis Virus / Q000276:immunology; D014036:Togaviridae Infections / Q000209:etiology / Q000276:immunology*
D001323:Autoantibodies; D004676:Myelin Basic Protein