Résumé :
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Communication n° 644 Background : HTLV-1 (Human T-lymphotropic Virus-1), the first retrovirus identified in man, infects about 20 million people around the world. It is the aetiological agent of two major diseases : Adult T Cell Leukemia and Tropical Spastic Paraparesis. Besides these diseases, it has been shown to be associated with inflammatory disorders such as myosities (polymyositis and inclusion body myositis). Although the pathogenesis of such HTLV-1-associated myosities remains unknown, a direct effect of cytokines or viral proteins in myocytotoxicity is suspected. Methods : We have developed an in vitro model to study the interactions between primary cultures of human muscle cells and HTLV-1 chronically infected cell lines. In parallel, observations were performed on muscle biopsies from HTLV-1 infected patients with myositis. Results : When HTLV-1 infected cell lines were added to myotubes, muscle fiber shrinking could be observed as early as day 1 after contact. Profound alterations in the desmin and vimentin intermediate filaments organization could be seen, in the absence of myotube infection. The viral protein Tax-1 could be detected by immunofluorescence in degenerating muscle fibers, and cytopathic changes were also observed when infected culture supernatants were added to the myotubes. Transduction of myotubes with a lentiviral vector containing the Tax-1 gene was able to reproduce such effects in vitro. Fiber atrophy and cytoskeletal disorganization were confirmed in muscle biopsies from HTLV-1-infected patients with myositis. Conclusions : these data indicate that the myocytotoxicity that is observed in HTLV-1-associated myopathies can be due to a direct effect of the Tax-1 protein expressed in the inflammatory infected cells, in the absence of myotube infection.
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