Human immunodeficiency virus type 1 (HIV-1) transactivator of transcription (Tat) is a potent mediator involved in the development of HIV-1-associated neurocognitive disorders (HAND). Tat is expressed even in the presence of antiretroviral therapy (ART) and is able to enter the central nervous system (CNS) through a variety of ways, where Tat can interact with microglia, astrocytes, brain microvascular endothelial cells, and neurons. The presence of low concentrations of extracellular Tat alone has been shown to lead to dysregulated gene expression, chronic cell activation, inflammation, neurotoxicity, and structural damage in the brain. The reported effects of Tat are dependent in part on the specific HIV-1 subtype and amino acid length of Tat used. HIV-1 subtype B Tat is the most common subtype in North American and therefore, most studies have been focused on subtype B Tat; however, studies have shown many genetic, biologic, and pathologic differences between HIV subtype B and subtype C Tat. This review will focus primarily on subtype B Tat where the full-length protein is 101 amino acids, but will also consider variants of Tat, such as Tat 72 and Tat 86, that have been reported to exhibit a number of distinctive activities with respect to mediating CNS damage and neurotoxicity.

人类免疫缺陷病毒 1 型 (HIV-1) 转录激活因子 (Tat) 是参与 HIV-1 相关神经认知障碍 (HAND) 发展的有效介质。即使在抗逆转录病毒疗法 (ART) 存在的情况下，Tat 也会表达，并且能够通过多种方式进入中枢神经系统 (CNS)，其中 Tat 可以与小胶质细胞、星形胶质细胞、脑微血管内皮细胞和神经元相互作用。已证明单独存在低浓度的细胞外 Tat 会导致基因表达失调、慢性细胞激活、炎症、神经毒性和大脑结构损伤。据报道，Tat 的影响部分取决于所用 Tat 的特定 HIV-1 亚型和氨基酸长度。HIV-1 B 亚型 Tat 是北美最常见的亚型，因此，大多数研究都集中在 B 亚型 Tat；然而，研究表明 HIV B 型和 C 型 Tat 之间存在许多遗传、生物学和病理学差异。本综述将主要关注全长蛋白质为 101 个氨基酸的 B 亚型 Tat，但也会考虑 Tat 的变体，例如 Tat 72 和 Tat 86，据报道，这些变体在介导中枢神经系统损伤和神经毒性。