Watanabe T
Department of Pathology, University of Tokyo, Japan.
Int J Hematol. 1997 Oct;66(3):257-78. doi: 10.1016/s0925-5710(97)00077-7.
HTLV-1-infection is associated with a variety of human diseases including adult T-cell leukemia (ATL) and non-neoplastic inflammatory diseases. The latter includes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 uveitis (HU) and other diseases with unestablished associations such as arthropathy, pneumopathy, dermatitis, exocrinopathy and myositis. ATL is defined as neoplastic clonal growth of HTLV-1-infected T-cells and is characterized by unique clinical features including hypercalcemia and severe organ infiltration of leukemic cells. HAM/TSP and HU are characterized by infiltration of HTLV-1-infected lymphocytes and dysregulated production of cytokines. Four major subtypes (genotypes) of HTLV-1 have been identified, which depend more on geography than disease. No disease-specific variants or mutations have been identified to date. A viral transcriptional regulator, Tax, regulates virus and cellular gene expression through binding to transcription factors or other cytoplasmic cellular molecules. Aberrant expression of cellular genes will affect fundamental cellular functions. The interaction between HTLV-1-infected cells and different kinds of cells in the host appears to be one of the basic mechanisms underlying the development of HTLV-1-associated diseases. This interaction may play a major role in determining tumorigenicity and in forming clinical features of the disease. Increased provirus load found in patients with HAM/TSP and HU results from clonal expansion of the HTLV-1-infected T-cells, which has been implicated in the pathogenesis of HTLV-1-associated diseases. Regulatory mechanisms of clonal growth remain unknown. Efforts to characterize functions of the viral proteins and the virus-infected cells and to understand the natural history of the HTLV-1-infection are required to determine the mechanisms of HTLV-1 viral pathogenesis.
人类嗜T淋巴细胞病毒1型（HTLV-1）感染与多种人类疾病相关，包括成人T细胞白血病（ATL）和非肿瘤性炎症性疾病。后者包括HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）和HTLV-1葡萄膜炎（HU）以及其他关联尚未明确的疾病，如关节病、肺病、皮炎、内分泌病和肌炎。ATL被定义为HTLV-1感染的T细胞的肿瘤性克隆生长，其特征为独特的临床特征，包括高钙血症和白血病细胞的严重器官浸润。HAM/TSP和HU的特征是HTLV-1感染的淋巴细胞浸润和细胞因子产生失调。已鉴定出HTLV-1的四种主要亚型（基因型），其更多地取决于地理位置而非疾病。迄今为止，尚未鉴定出疾病特异性变体或突变。一种病毒转录调节因子Tax通过与转录因子或其他细胞质细胞分子结合来调节病毒和细胞基因表达。细胞基因的异常表达将影响基本的细胞功能。HTLV-1感染细胞与宿主中不同类型细胞之间的相互作用似乎是HTLV-1相关疾病发生的基本机制之一。这种相互作用可能在决定致瘤性和形成疾病临床特征方面起主要作用。在HAM/TSP和HU患者中发现的前病毒载量增加是由HTLV-1感染的T细胞的克隆扩增引起的，这与HTLV-1相关疾病的发病机制有关。克隆生长的调节机制仍然未知。需要努力表征病毒蛋白和病毒感染细胞的功能，并了解HTLV-1感染的自然史，以确定HTLV-1病毒发病机制。
