Department of Oncology and Surgical Sciences, University of Padova, Padova, Italy.
Blood. 2011 May 5;117(18):4855-9. doi: 10.1182/blood-2010-11-316463. Epub 2011 Mar 11.
Human T-cell leukemia virus type 1 (HTLV-1) codes for 9 alternatively spliced transcripts and 2 major regulatory proteins named Tax and Rex that function at the transcriptional and posttranscriptional levels, respectively. We investigated the temporal sequence of HTLV-1 gene expression in primary cells from infected patients using splice site-specific quantitative RT-PCR. The results indicated a two-phase kinetics with the tax/rex mRNA preceding expression of other viral transcripts. Analysis of mRNA compartmentalization in cells transfected with HTLV-1 molecular clones demonstrated the strict Rex-dependency of the two-phase kinetics and revealed strong nuclear retention of HBZ mRNAs, supporting their function as noncoding transcripts. Mathematical modeling underscored the importance of a delay between the functions of Tax and Rex, which was supported by experimental evidence of the longer half-life of Rex. These data provide evidence for a temporal pattern of HTLV-1 expression and reveal major differences in the intracellular compartmentalization of HTLV-1 transcripts.
人类 T 细胞白血病病毒 1 型（HTLV-1）编码 9 种不同剪接的转录本和 2 种主要的调节蛋白，分别命名为 Tax 和 Rex，它们分别在转录和转录后水平发挥作用。我们使用剪接位点特异性定量 RT-PCR 研究了感染患者原代细胞中 HTLV-1 基因表达的时间顺序。结果表明存在两相动力学，tax/rex mRNA 先于其他病毒转录本表达。用 HTLV-1 分子克隆转染细胞的 mRNA 区室分析表明，两相动力学具有严格的 Rex 依赖性，并显示 HBZ mRNAs 强烈的核保留，支持它们作为非编码转录本的功能。数学模型强调了 Tax 和 Rex 功能之间的延迟的重要性，这得到了 Rex 半衰期较长的实验证据的支持。这些数据为 HTLV-1 表达的时间模式提供了证据，并揭示了 HTLV-1 转录本在细胞内区室化方面的主要差异。
