The HIV-1 Tat transactivator protein: a therapeutic target?

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.