Characterization of the inflammatory response during acute measles encephalitis in NSE-CD46 transgenic mice.
Expression of the human measles virus receptor, CD46, in the murine central nervous system allows infection and replication by wild-type human measles virus (MV) strains (Rall, G.F., Manchester, M., Daniels L.R., Callahan, E., Belman, A., Oldstone, M.B.A., 1997. A transgenic mouse model for measles virus infection of the brain. Proc. Natl. Acad. Sci. U.S.A. 94, 2243-2248). MV replicates in neurons in focal lesions of the cortex, hippocampus and thalamus, leading to death of the animals. In MV-infected CD46 transgenic mice, infiltration of CD4+ and CD8+ T-lymphocytes, B-lymphocytes and macrophages was seen. Upregulation of MHC class I and class II molecules was observed, along with reactive astrocytosis and microgliosis. Increased chemokine mRNAs, especially RANTES and IP-10, and cytokine RNAs IL-6, TNF-alpha, and IL1-beta were observed. Apoptosis of neurons also was increased. No MV replication or inflammation was seen in similarly inoculated nontransgenic littermates. These results further characterize the MV-induced encephalitis in CD46 transgenic mice and highlight similarities to MV infection of the human CNS.
Manchester
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M
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA. marim@scripps.edu
Eto
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Oldstone
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D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D005911:Gliosis / Q000209:etiology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D008457:Measles / Q000473:pathology / Q000503:physiopathology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics
D015703:Antigens, CD; D015415:Biomarkers; C497857:CD46 protein, human; D018925:Chemokines; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins