Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Blood. 2013 Aug 1;122(5):715-25. doi: 10.1182/blood-2013-03-493718. Epub 2013 Jun 17.
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL), and the viral oncoprotein Tax plays key roles in the immortalization of human T cells, lifelong persistent infection, and leukemogenesis. We herein identify the ubiquitin-specific protease 10 (USP10) as a Tax-interactor in HTLV-1-infected T cells. USP10 is an antistress factor against various environmental stresses, including viral infections and oxidative stress. On exposure to arsenic, an oxidative stress inducer, USP10 is recruited into stress granules (SGs), and USP10-containing SGs reduce reactive oxygen species (ROS) production and inhibit ROS-dependent apoptosis. We found that interaction of Tax with USP10 inhibits arsenic-induced SG formation, stimulates ROS production, and augments ROS-dependent apoptosis in HTLV-1-infected T cells. These findings suggest that USP10 is a host factor that inhibits stress-induced ROS production and apoptosis in HTLV-1-infected T cells; however, its activities are attenuated by Tax. A clinical study showed that combination therapy containing arsenic is effective against some forms of ATL. Therefore, these findings may be relevant to chemotherapy against ATL.
人 T 细胞白血病病毒 1 型（HTLV-1）是成人 T 细胞白血病（ATL）的病因，病毒癌蛋白 Tax 在人类 T 细胞永生化、终身持续感染和白血病发生中发挥关键作用。我们在此鉴定出泛素特异性蛋白酶 10（USP10）是 HTLV-1 感染 T 细胞中的 Tax 相互作用蛋白。USP10 是一种对抗各种环境应激的应激因子，包括病毒感染和氧化应激。在砷暴露下，一种氧化应激诱导剂，USP10 被募集到应激颗粒（SGs）中，并且含有 USP10 的 SGs 减少活性氧（ROS）的产生并抑制 ROS 依赖性细胞凋亡。我们发现 Tax 与 USP10 的相互作用抑制砷诱导的 SG 形成，刺激 ROS 的产生，并增强 HTLV-1 感染的 T 细胞中 ROS 依赖性细胞凋亡。这些发现表明，USP10 是一种宿主因子，可抑制 HTLV-1 感染的 T 细胞中应激诱导的 ROS 产生和细胞凋亡；然而，其活性被 Tax 减弱。一项临床研究表明，含有砷的联合疗法对某些形式的 ATL 有效。因此，这些发现可能与针对 ATL 的化疗有关。
