Antibodies directed against rubella virus induce demyelination in aggregating rat brain cell cultures.
To link the presence of intrathecal virus-specific oligoclonal immunoglobulin G (IgG) in multiple sclerosis patients to a demyelinating activity, aggregating rat brain cell cultures were treated with antibodies directed against two viruses, namely, rubella (RV) and hepatitis B (HB). Anti-RV antibodies in the presence of complement decreased myelin basic protein concentrations in a dose-dependent manner, whereas anti-HB antibodies had no effect. A similar but less pronounced effect was observed on the enzymatic activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, which is enriched in noncompact membranes of oligodendrocytes. These effects were comparable to those in cultures treated with antibodies directed against myelin oligodendrocyte glycoprotein (MOG), previously found to be myelinotoxic both in vitro and in vivo. Sequence homologies were found between structural glycoprotein E(2) of RV and MOG, suggesting that demyelination was due to molecular mimicry. To support the hypothesis that demyelination was caused by anti-RV IgG that recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration that anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and that both revealed by Western blot a 28 kDa protein in CNS myelin, a molecular weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelination.
Besson Duvanel
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Laboratory of Neurochemistry, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Honegger
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Matthieu
J M
JM
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D000918:Antibody Specificity / Q000276:immunology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002449:Cell Aggregation / Q000276:immunology; D002478:Cells, Cultured / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D003429:Cross Reactions / Q000276:immunology; D005333:Fetus; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D018992:Myelin-Associated Glycoprotein / Q000172:deficiency / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051381:Rats; D012412:Rubella virus / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D007074:Immunoglobulin G; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014759:Viral Envelope Proteins; C061827:E2 envelope protein, Rubella virus