A retroviral element (multiple sclerosis-associated retrovirus, MSRV) defining a family of genetically inherited endogenous retroviruses (human endogenous retrovirus type W, HERV-W) has been characterized in cell cultures from patients with multiple sclerosis. Recently, MSRV retroviral particles or the envelope recombinant protein were shown to display superantigen activity in vitro, but no animal model has yet been set up for studying the pathogenicity of this retrovirus. In the present study, the pathogenicity of different sources of MSRV retroviral particles has been evaluated in a hybrid animal model: severe combined immunodeficiency (SCID) mice grafted with human lymphocytes and injected intraperitoneally with MSRV virion or mock controls. MSRV-injected mice presented with acute neurological symptoms and died within 5 to 10 days post injection. Necropsy revealed disseminated and major brain hemorrhages, whereas control animals did not show abnormalities (P <.001). In ill animals, reverse transcriptase-polymerase chain reaction (RT-PCR) analyses showed circulating MSRV RNA in serum, whereas overexpression of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma was evidenced in spleen RNA. Neuropathological examination confirmed that hemorrhages occurred prior to death in multifocal areas of brain parenchyma and meninges. Further series addressed the question of immune-mediated pathogenicity, by inoculating virion to SCID mice grafted with total and T lymphocyte-depleted cells in parallel: dramatic and statistically significant reduction in the number of affected mice was observed in T-depleted series (P <.001). This in vivo study suggests that MSRV retroviral particles from MS cultures have potent immunopathogenic properties mediated by T cells compatible with the previously reported superantigen activity in vitro, which appear to be mediated by an overexpression of proinflammatory cytokines.

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The human HLA-DQ alpha probe was used to screen genomic and cDNA libraries constructed from a rabbit T-cell line. Clones containing highly homologous sequences were obtained from both libraries and their sequences were determined. The organization of the RLA-DQ gene was determined by comparison of the nucleotide sequences of the genomic clone to that of the corresponding cDNA clone. This analysis allowed assignment of the complete structure of the RLA-DQ alpha chain. Comparisons with human and mouse class II products revealed that RLA-DQ is more closely related to HLA-DQ/DX than to H-2A. In contrast to the DQ/DX region of man, which contains at least two distinct alpha genes, the rabbit genome contains a single DQ gene which is equally distant from the HLA-DQ or -DX genes. The rabbit DQ alpha gene, like human HLA-DQ, is transcribed in T cells.

Letter to the editor MSRV, Syncytin and the role of endogenous retroviral proteins in demyelinationSir -A major study on the pathogenesis of multiple sclerosis was published in the October issue of Nature Neuroscience accompanied by a flurry of media reports.The study by Antony and colleagues 1 describes the

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