Division of Molecular Oncology, Washington University School of Medicine, St. Louis, MO, USA.
Virology. 2011 Feb 20;410(2):307-15. doi: 10.1016/j.virol.2010.11.019. Epub 2010 Dec 21.
Human T-cell leukemia virus type 1 (HTLV-1) basic leucine zipper factor (HBZ) is transcribed from the antisense genomic DNA strand and functions differently in its RNA and protein forms. To distinguish between the roles of hbz mRNA and HBZ protein, we generated mutants in a proviral clone that specifically disrupt the hbz gene product. A proviral clone with a splice acceptor mutation that disrupts expression of the predominant hbz mRNA resulted in lower levels of tax mRNA. Heterologous hbz expression restored Tax activity in cells expressing this mutant clone. In contrast, proviral mutants that disrupt HBZ protein did not affect levels of tax mRNA. Expression of hbz resulted in lower levels of p30(II) mRNA. Mutation of p30(II) overcame the effects of the splice acceptor mutation of hbz, and restored tax expression. Thus, there is a complex interplay of viral regulatory proteins controlling levels of HTLV-1 gene expression.
人类 T 细胞白血病病毒 1 型（HTLV-1）碱性亮氨酸拉链因子（HBZ）由反义基因组 DNA 链转录，其 RNA 和蛋白质形式的功能不同。为了区分 hbz mRNA 和 HBZ 蛋白的作用，我们在原病毒克隆中生成了专门破坏 hbz 基因产物的突变体。带有剪接受体位点突变的原病毒克隆破坏了主要 hbz mRNA 的表达，导致 tax mRNA 水平降低。异源 hbz 表达恢复了表达这种突变克隆的细胞中的 Tax 活性。相比之下，破坏 HBZ 蛋白的原病毒突变体不会影响 tax mRNA 的水平。hbz 的表达导致 p30(II)mRNA 的水平降低。p30(II)的突变克服了 hbz 的剪接受体位点突变的影响，并恢复了 tax 的表达。因此，病毒调节蛋白之间存在复杂的相互作用，控制 HTLV-1 基因表达的水平。
