Muscle wasting induced by HTLV-1 tax-1 protein -: An in vitro and in vivo study
Muscle wasting induced by HTLV-1 tax-1 protein -: An in vitro and in vivo study
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DOI：
10.1016/s0002-9440(10)61245-x
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发表时间：
2005-12-01
影响因子：
6
通讯作者：
Ceccaldi, PE
中科院分区：
文献类型：
--
作者：
Ozden, S;Mouly, V;Ceccaldi, PE
除了热带痉挛性下肢轻瘫/人类T细胞白血病病毒1型（HTLV-1）相关的脊髓病，人类逆转录病毒HTLV-1引起炎症性疾病，如肌炎。虽然HTLV-1相关性肌炎的发病机制尚不清楚，但怀疑细胞因子或病毒蛋白在肌细胞毒性中的直接作用。我们已经建立了一个体外细胞培养模型来研究原代人肌细胞和HTLV-1慢性感染细胞之间的相互作用。当将HTLV-1感染的细胞系加入分化的肌肉培养物中时，早在接触后1天就观察到细胞病变变化，如纤维收缩。这伴随着结蛋白和波形蛋白组织的改变，发生在没有肌细胞感染的情况下，但Tax-1存在于肌管中。当将感染的培养上清液加入肌细胞中时，也观察到细胞病变。在两名HTLV-1感染的肌炎患者的肌肉活检中证实了纤维萎缩和细胞骨架紊乱。用含有HTLV-1 Tax基因的慢病毒载体转导培养的肌细胞在体外再现了这种效果。目前的数据表明，在HTLV-1相关肌病中观察到的肌细胞毒性可能是由于在没有肌细胞感染的情况下，在感染的炎性细胞中表达的Tax-1蛋白的直接作用。
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.