Expression of human HLA-B27 transgene alters susceptibility to murine Theiler's virus-induced demyelination.
Infection of certain strains of mice with Theiler's murine encephalomyelitis virus results in persistence of virus and an immune-mediated primary demyelination in the central nervous system that resembles multiple sclerosis. Because susceptibility/resistance to demyelination in B10 congeneic mice maps strongly to class I MHC genes (D region) we tested whether expression of a human class I MHC gene (HLA-B27) would alter susceptibility to Theiler's murine encephalomyelitis virus-induced demyelination. Transgenic HLA-B27 mice were found to co-express human and endogenous mouse class I MHC genes by flow microfluorimetry analysis of PBL. In the absence of the human transgene, H-2stf, or v mice but not H-2b mice had chronic demyelination and persistence of virus at 45 days after infection. No difference in degree of demyelination, meningeal inflammation, or virus persistence was seen between transgenic HLA-B27 and nontransgenic littermate mice of H-2f or H-2v haplotype. In contrast, H-2s (HLA-B27+) mice showed a dramatic decrease in extent of demyelination and number of virus-Ag+ cells in the spinal cord compared with H-2s (HLA-B27-) littermate mice. In addition, none of the eight H-2s mice homozygous for HLA-B27 gene had spinal cord lesions even though infectious virus was isolated chronically from their central nervous system. Expression of HLA-B27 transgene did not interfere with the resistance to demyelination normally observed in B10 (H-2b) mice. These experiments demonstrate that expression of a human class I MHC gene can modulate a virus-induced demyelinating disease process in the mouse.
Rodriguez
M
M
Department of Neurology, Mayo Clinic, Rochester, MN 55905.
Nickerson
C
C
Patick
A K
AK
David
C S
CS
D000818:Animals; D015139:Blotting, Southern; D003711:Demyelinating Diseases / Q000209:etiology / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D015796:HLA-B27 Antigen / Q000096:biosynthesis / Q000235:genetics*; D004680:Maus Elberfeld virus; D051379:Mice; D008822:Mice, Transgenic; D010375:Pedigree; D013601:T-Lymphocytes / Q000276:immunology
D015796:HLA-B27 Antigen