Muscle wasting induced by HTLV-1 tax-1 protein: an in vitro and in vivo study

Besides tropical spastic paraparesis/human T-cell leukemia virus type-1 (HTLV-1)-associated myelopathy, the human retrovirus HTLV-1 causes inflammatory disorders such as myositis. Although the pathogenesis of HTLV-1-associated myositis is primarily unknown, a direct effect of cytokines or viral proteins in myocytotoxicity is suspected. We have developed an in vitro cell culture model to study the interactions between primary human muscle cells and HTLV-1 chronically infected cells. When HTLV-1-infected cell lines were added to differentiated muscle cultures, cytopathic changes such as fiber shrinking were observed as early as 1 day after contact. This was accompanied by alterations in desmin and vimentin organization, occurring in the absence of muscle cell infection but with Tax-1 present in myotubes. Cytopathic changes were also observed when infected culture supernatants were added to the muscle cells. Fiber atrophy and cytoskeletal disorganization were confirmed in muscle biopsies from two HTLV-1-infected patients with myositis. Transduction of cultured muscle cells with a lentiviral vector containing the HTLV-1 Tax gene reproduced such effects in vitro. The present 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 infected inflammatory cells, in the absence of muscle cell infection.