Fulcher Alex J, Jans David A
Dept. for Biochemistry and Mol. Biol., Monash University, Australia.
IUBMB Life. 2003 Dec;55(12):669-80. doi: 10.1080/15216540310001643440.
The human immunodeficiency virus-1 (HIV-1), the causative agent of autoimmune deficiency syndrome (AIDS) is a major health problem world-wide. Central to HIV infection is the transactivator protein Tat, that plays a critical role in the nucleus during the HIV infectious cycle, by binding the transactivation-responsive region (TAR) and thereby enhancing transcriptional elongation. Tat appears to gain nuclear entry through a novel mechanism, independent of the normal cellular importin/Ran-dependent pathways, and regulated by a cytoplasmic retention mechanism. Since blocking Tat nuclear import is likely to prevent HIV infection, detailed delineation of Tat's nuclear import pathway is critical to assessing its viability as a therapeutic target. Other feasible anti-HIV therapies include approaches to inhibit Tat-TAR interaction.
人类免疫缺陷病毒1型（HIV-1）是获得性免疫缺陷综合征（AIDS）的病原体，是全球主要的健康问题。HIV感染的核心是反式激活蛋白Tat，它在HIV感染周期中于细胞核内发挥关键作用，通过结合反式激活应答区域（TAR）从而增强转录延伸。Tat似乎通过一种新机制进入细胞核，该机制独立于正常的细胞输入蛋白/ Ran依赖性途径，并受细胞质滞留机制调控。由于阻断Tat的核输入可能会预防HIV感染，详细描绘Tat的核输入途径对于评估其作为治疗靶点的可行性至关重要。其他可行的抗HIV疗法包括抑制Tat-TAR相互作用的方法。
