Department of Clinical and Molecular Biomedicine, Division of Infectious Diseases, University of Catania, Via Palermo 636, Zip 95125, ARNAS Garibaldi Nesima, Catania, Italy.
Curr Drug Targets. 2013 Jun 1;14(6):648-52. doi: 10.2174/1389450111314060005.
Sirtuins are a family of NAD+-dependent protein deacetylases, which regulate cell survival and energy metabolism, inflammation and cancer. Recent studies have shown that sirtuin-1 (SIRT1) modulates Human Immunodeficiency Virus (HIV)-1 transcription. The HIV-1 Tat protein is a substrate for the deacetylase activity of SIRT1; SIRT1 recycles Tat to its unacetylated form, catalyzing a fundamental step to start new cycles of viral transcription. Moreover, Tat has been reported to promote T-cell hyperactivation by suppressing SIRT1 activity. In fact, Tat blocks the ability of SIRT1 to deacetylate lysine 310 in the p65 subunit of nuclear factor- κB (NF- κB) by interacting with the deacetylase domain of SIRT1. This mechanism leads therefore to the hyperactivation of NF- κB proinflammatory pathway and may likely contribute to the chronic immune activation state of HIV-infected individuals. In the present review we first briefly describe the biological functions of sirtuins, then we delineate the interplay between SIRT1 and HIV-1 and discuss the potential role of SIRT1 as a pharmacological target of HIV-1 replication.
沉默调节蛋白是一类 NAD+依赖的蛋白去乙酰化酶，可调节细胞存活和能量代谢、炎症和癌症。最近的研究表明，沉默调节蛋白 1（SIRT1）可调节人类免疫缺陷病毒（HIV）-1 的转录。HIV-1 Tat 蛋白是 SIRT1 去乙酰化酶活性的底物；SIRT1 将 Tat 回收到未乙酰化的形式，催化了开始新的病毒转录循环的基本步骤。此外，Tat 通过抑制 SIRT1 活性来促进 T 细胞的过度激活。事实上，Tat 通过与 SIRT1 的去乙酰化酶结构域相互作用，阻止 SIRT1 对核因子-κB（NF-κB）p65 亚基中赖氨酸 310 的去乙酰化。该机制导致 NF-κB 促炎途径的过度激活，可能有助于 HIV 感染者的慢性免疫激活状态。在本综述中，我们首先简要描述了沉默调节蛋白的生物学功能，然后阐述了 SIRT1 与 HIV-1 之间的相互作用，并讨论了 SIRT1 作为 HIV-1 复制的药理学靶点的潜在作用。
