人T细胞白血病病毒1型反义链基因HBZ mRNA的细胞核内定位、分子机制以及生理意义

人T细胞白血病病毒1型（HTLV-1）是首个被发现的人逆转录病毒，其感染可以导致恶性程度极高的成人T细胞白血病（ATL）。HTLV-1编码一个反义链基因HBZ，其mRNA被认为具有编码蛋白以外的调节功能，但在HTLV-1致癌过程中的作用机制不明。为了明确HBZ mRNA在HTLV-1感染与致癌过程中的角色与功能，本研究利用高度灵敏的RNA荧光免疫原位杂交（RNA-FISH）系统调查了HTLV-1感染细胞和ATL临床标本，发现HBZ mRNA定位于细胞核内。通过对HBZ mRNA的沉默，发现HTLV-1感染细胞的生长受到了抑制。未来计划进一步完善HBZ mRNA定位于细胞核内的分子机制，并通过体外和体内多种途径深入挖掘HBZ mRNA在ATL发病过程中的功能。该研究将对HBZ基因作为mRNA参与的HTLV-1致癌机制提供全新的认识，并将促进基于HBZ mRNA的ATL靶向治疗手段的开发。

HTLV-1 is the first human retrovirus to have been identified. HTLV-1 infection leads to the development of ATL, which is a highly aggressive T-cell leukemia. HTLV-1 encodes an antisense gene named HBZ, whose mRNA has been reported to harbor regulatory functions independent from its protein-coding potential. However, it remains unclear how HBZ mRNA contributes to the oncogenesis induced by HTLV-1. To reveal the role and function of HBZ mRNA in HTLV-1 infection and oncogenesis, we employed the highly sensitive RNA-FISH technology to investigate HTLV-1 infected cell lines and ATL cases. In contrast to its mRNA nature, we found HBZ mRNA was predominantly localized in the nucleus. Moreover, knocking down nucleus-localized HBZ mRNA suppressed the proliferation of HTLV-1 infected cells. In future, we will try to find out the underlying mechanism of the nuclear localization of HBZ mRNA, and to investigate the functions of HBZ mRNA in ATL development both in vitro and in vivo. This study will shed light on the HBZ mRNA-mediated HTLV-1 oncogenesis, and promote the development of targeted therapy of ATL based on HBZ mRNA.