人类T淋巴细胞白血病病毒1型（HTLV-1）作为第一个分离鉴定的与癌症相关的逆转录病毒，全球约有2000万感染者，是导致ATL以及HAM/TSP的病原体。目前ATL和HAM/TSP的发病机制尚不清楚，临床上也没有有效药物和特异性的治疗手段。研究表明病毒反义蛋白HBZ的主要亚型sHBZ是该病毒诱发细胞恶性增殖的主要蛋白。我们前期结果发现sHBZ定位在核仁内并且与核仁蛋白B23相互作用，与sHBZ诱发细胞恶性增殖密切相关。本课题将研究B23与HBZ相互作用以及涉及的关键区域与位点，探索B23、sHBZ核仁定位以及B23与sHBZ互作在ATL发生中的作用及其分子机制，分析sHBZ与ATL样本中B23突变的相关性，以期阐明B23蛋白与sHBZ参与ATL发生的分子机制。本研究旨在解析sHBZ诱导的T细胞恶性生长以及其在HTLV-1诱发ATL和HAM/TSP的新机制，为研发相关疾病治疗手段提供靶点。

Human T-cell Leukemia Virus type 1 was the first isolated oncogenic retrovirus. The worldwide prevalence for HTLV-1 has recently been estimated to 20 million. HTLV-1 has been associated with different inflammatory-based disease, including the prominent HTLV-1-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Current treatments have limited efficacy on patients suffering from the acute form of ATL and HAM/TSP. The HTLV-1 bZIP (HBZ) gene, is expressed as a major isoform known as sHBZ and is thought to contribute to the proliferative ability of infected malignant cells and the aggressive ATL. Based on our previous study, the nucleolar localization of sHBZ is associated with nucleolus-residing proteins, which mediates the proliferative ability of infected malignant cells. This project will focus on the investigation in the interaction between sHBZ and B23 and in the new oncogenic mechanism of HTLV-1-associated HAM/TSP and / or ATL. These studies will ultimately provide new avenues for more targeted treatment against ATL and HAM/TSP.