Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virus-specific CD8+ T cells, and disease severity in HTLV-1-associated myelopathy (HAM/TSP)
Correlation of human T-cell lymphotropic virus type 1 (HTLV-1) mRNA with proviral DNA load, virus-specific CD8+ T cells, and disease severity in HTLV-1-associated myelopathy (HAM/TSP)
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DOI：
10.1182/blood.v99.1.88
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发表时间：
2002-01-01
期刊：
影响因子：
20.3
通讯作者：
Jacobson, S
中科院分区：
文献类型：
--
作者：
Yamano, Y;Nagai, M;Jacobson, S
为研究人类嗜T淋巴细胞病毒1型（HTLV-1）感染后病毒表达的变化，建立了实时定量RT-PCR方法，应用ABI Prism 7700全自动测序系统检测HTLV-1 tax mRNA。使用该系统，将HTLV-1 Tax mRNA载量与HTLV-1前病毒DNA载量、HTLV-1 Tax蛋白表达、HTLV-1 Tax特异性CD 8（+）T细胞频率和HTLV-1相关脊髓病/热带痉挛性轻瘫（HAM/TSP）的疾病严重程度进行比较。该方法是一种灵敏、特异的HTLV-1 tax mRNA精确定量技术。HAM/TSP患者中HTLV-1 tax mRNA总量和HTLV-1感染细胞中的mRNA表达水平（mRNA/DNA比）高于无症状HTLV-1携带者。HTLV-1 tax mRNA载量与体外HTLV-1前病毒DNA载量、体外Tax蛋白表达和体外Tax特异性CD 8（+）T细胞频率相关。HTLV-1 tax mRNA载量也与HAM/TSP患者的疾病严重程度相关。这些数据表明，HTLV-1表达增加在HAM/TSP的发病机制中起重要作用，HTLV-1 tax mRNA水平可能是HAW TSP患者疾病进展的有用预测因子。
To investigate the role of viral expression in individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1), a real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) of HTLV-1 tax messenger RNA (mRNA) using ABI Prism 7700 Sequence Detection System was developed. Using this system, the HTLV-1 tax mRNA load was compared with HTLV-1 proviral DNA load, HTLV-1 Tax protein expression, HTLV-1 Tax-specific CD8(+) T-cell frequency, and disease severity of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). This approach was a sensitive and specific technique for the precise quantification of HTLV-1 tax mRNA. The total amount of HTLV-1 tax mRNA and mRNA expression level in HTLV-1-infected cells (mRNA/DNA ratio) were higher in HAM/TSP patients than in asymptomatic HTLV-1 carriers. The HTLV-1 tax mRNA load correlated with the HTLV-1 proviral DNA load ex vivo, the Tax protein expression in vitro, and the Tax-specific CD8(+) T-cell frequency ex vivo. The HTLV-1 tax mRNA load also correlated with disease severity in HAM/TSP patients. These data suggest that increased HTLV-1 expression plays an important role In the pathogenesis of HAM/TSP, and the HTLV-1 tax mRNA level could be a useful predictor of disease progression In patients with HAW TSP.