Lin Hsin-Ching, Simon Peter J, Ysla Riza M, Zeichner Steven L, Brewer Gary, Rabson Arnold B
Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 89 French Street, New Brunswick, NJ 08903, USA; Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Virology. 2017 Aug;508:7-17. doi: 10.1016/j.virol.2017.04.029. Epub 2017 May 4.
Regulation of expression of HTLV-1 gene products from integrated proviruses plays an important role in HTLV-1-associated disease pathogenesis. Previous studies have shown that T cell receptor (TCR)- and phorbol ester (PMA) stimulation of chronically infected CD4 T cells increases the expression of integrated HTLV-1 proviruses in latently infected cells, however the mechanism remains unknown. Analysis of HTLV-1 RNA and protein species following PMA treatment of the latently HTLV-1-infected, FS and SP T cell lines demonstrated rapid induction of tax/rex mRNA. This rapid increase in tax/rex mRNA was associated with markedly enhanced tax/rex mRNA stability while the stability of unspliced or singly spliced HTLV-1 RNAs did not increase. Tax/rex mRNA in the HTLV-1 constitutively expressing cell lines exhibited high basal stability even without PMA treatment. Our data support a model whereby T cell activation leads to increased HTLV-1 gene expression at least in part through increased tax/rex mRNA stability.
来自整合前病毒的HTLV-1基因产物表达调控在HTLV-1相关疾病发病机制中起重要作用。先前的研究表明，T细胞受体（TCR）和佛波酯（PMA）刺激慢性感染的CD4 T细胞可增加潜伏感染细胞中整合的HTLV-1前病毒的表达，但其机制仍不清楚。对潜伏感染HTLV-1的FS和SP T细胞系进行PMA处理后，对HTLV-1 RNA和蛋白质种类的分析表明tax/rex mRNA迅速被诱导。tax/rex mRNA的这种快速增加与tax/rex mRNA稳定性的显著增强相关，而未剪接或单剪接的HTLV-1 RNA的稳定性并未增加。在HTLV-1组成型表达细胞系中，即使未经PMA处理，tax/rex mRNA也表现出高基础稳定性。我们的数据支持一种模型，即T细胞激活至少部分通过增加tax/rex mRNA稳定性导致HTLV-1基因表达增加。
