Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells
Proviral status of HTLV-1 integrated into the host genomic DNA of adult T-cell leukemia cells
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DOI：
10.1111/j.1365-2257.2005.00698.x
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发表时间：
2005-08-01
期刊：
影响因子：
--
通讯作者：
Yamada, Y
中科院分区：
文献类型：
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作者：
Kamihira, S;Sugahara, K;Yamada, Y
人类t细胞白血病病毒1型（HTLV-1）是成人t细胞白血病（ATL）的病原，白血病细胞总是在同一序列位点携带单克隆整合到宿主基因组中的前病毒基因组，称为单克隆整合。采用Southern blot杂交（SBH）和测序标记位点聚合酶链反应（pcr）检测350例疑似ATL患者的558例临床标本的原病毒状态。根据SBH，使用EcoR1和Pst1，来自241例患者的321份标本（57.5%）显示单克隆整合阳性结果。241例患者中，完整原病毒（c型）136例（56.4%），缺陷原病毒（d型）62例（25.7%），多带原病毒（m型）43例（17.8%）。ATL的D-型和m型发生率依次为阴燃型、慢性亚型和急性亚型，提示这种异常的前病毒状态是在多步癌变过程中产生的，对疾病的恶性行为具有重要的临床意义。此外，我们的数据显示，原病毒基因组的部分缺失首先在gag区域开始，然后扩散到pol和env区域，而长末端重复和pX区域几乎总是保守的。这些结果表明，分析ATL和HTLV-1的前病毒状态可为ATL和HTLV-1的病理诊断和病毒学肿瘤学提供有用的信息，特别是pX基因在肿瘤发生中的重要作用。
Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and leukemic cells always carry the proviral genome monoclonally integrated into their host genomes at the same sequence site, designated as the monoclonal integration. Using Southern blot hybridization (SBH) and sequenced tagged site polymerase chain reaction assays, we examined the proviral status in 558 clinical specimens from 350 patients who are suspected to have ATL. A total of 321 specimens (57.5%) from 241 patients showed positive results for the monoclonal integration according to SBH, using EcoR1 and Pst1. The 241 patients consisted of 136 patients (56.4%) with the complete provirus (C-type), 62 patients (25.7%) with a defective provirus (D-type), and 43 patients (17.8%) with multibands (M-type). The incidence of the D- and M-types were in the order of smoldering, chronic, and acute subtypes of ATL, suggesting that such an aberrant proviral status is generated on the way to multistep carcinogenesis and is subsequently clinically important for the malignant behavior of the disease. Moreover, our data showed that the partial deletion of the proviral genome is initiated first at the site of the gag region and spreads into the sites of the pol and env regions, whereas the long terminal repeats and pX regions are almost always conserved. These results suggest that analysis of the proviral status provides useful diagnostic and virologic-oncological information about ATL and HTLV-1 pathology, especially the important role of pX gene in tumorigenesis.