Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Viruses. 2011 Aug;3(8):1485-500. doi: 10.3390/v3081485. Epub 2011 Aug 18.
Adult T-cell leukemia (ATL) is one of the primary diseases caused by Human T-cell Leukemia Virus type 1 (HTLV-1) infection. The virally-encoded Tax protein is believed to initiate early events in the development of this disease, as it is able to promote immortalization of T-cells and transformation of other cell types. These processes may be aided by the ability of the viral protein to directly deregulate expression of specific cellular genes through interactions with numerous transcriptional regulators. To identify gene promoters where Tax is localized, we isolated Tax-DNA complexes from an HTLV-1-infected T-cell line through a chromatin immunoprecipitation (ChIP) assay and used the DNA to probe a CpG island microarray. A site within the RNASET2 gene was found to be occupied by Tax. Real-time PCR analysis confirmed this result, and transient expression of Tax in uninfected cells led to the recruitment of the viral protein to the promoter. This event correlated with a decrease in the level of RNase T2 mRNA and protein, suggesting that Tax represses expression of this gene. Loss of RNase T2 expression occurs in certain hematological malignancies and other forms of cancer, and RNase T2 was recently reported to function as a tumor suppressor. Consequently, a reduction in the level of RNase T2 by Tax may play a role in ATL development.
成人 T 细胞白血病（ATL）是由人类 T 细胞白血病病毒 1 型（HTLV-1）感染引起的主要疾病之一。病毒编码的 Tax 蛋白被认为是引发这种疾病早期事件的原因，因为它能够促进 T 细胞的永生化和其他细胞类型的转化。这种过程可能是由于病毒蛋白通过与众多转录调节剂相互作用，直接调节特定细胞基因的表达所致。为了确定 Tax 定位的基因启动子，我们通过染色质免疫沉淀（ChIP）检测从 HTLV-1 感染的 T 细胞系中分离出 Tax-DNA 复合物，并使用该 DNA 探测 CpG 岛微阵列。发现 RNASET2 基因内的一个位点被 Tax 占据。实时 PCR 分析证实了这一结果，并且在未感染的细胞中转染 Tax 导致病毒蛋白募集到启动子。这一事件与 RNase T2 mRNA 和蛋白水平的降低相关，表明 Tax 抑制了该基因的表达。在某些血液恶性肿瘤和其他形式的癌症中，RNase T2 的表达缺失，并且最近报道 RNase T2 作为一种肿瘤抑制因子发挥作用。因此，Tax 降低 RNase T2 的水平可能在 ATL 发展中起作用。
