Antibodies directed against rubella virus induce demyelination in aggregating rat brain cell cultures

To link the presence of intrathecal virus-specific oligoclonal immunoglobul in G (IgG) in multiple sclerosis patients to a demyelinating activity, aggr egating rat brain cell cultures were treated with antibodies directed again st two viruses, namely, rubella (RV) and hepatitis B (NB). Anti-RV antibodi es in the presence of complement decreased myelin basic protein concentrati ons 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 noncom pact 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 tha t recognized an MOG epitope, we found that anti-RV antibodies depleted MOG in a dose-dependent manner. Further evidence came from the demonstration th at anti-RV and anti-MOG IgG colocalized on oligodendrocyte processes and th at both revealed by Western blot a 28 kDa protein in CNS myelin, a molecula r weight corresponding to MOG. These findings suggest that a virus such as RV exhibiting molecular mimicry with MOG can trigger an autoimmune demyelin ation. (C) 2001 Wiley-Liss, Inc.