Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.
Cytokine Growth Factor Rev. 2012 Aug-Oct;23(4-5):159-72. doi: 10.1016/j.cytogfr.2012.05.003. Epub 2012 Jul 4.
Antiretroviral therapy (ART) has proved highly effective in suppressing HIV-1 replication and disease progression. Nevertheless, ART has failed to eliminate the virus from infected individuals. The main obstacle to HIV-1 eradication is the persistence of cellular viral reservoirs. Therefore, the "shock-and-kill" strategy was proposed consisting of inducing HIV-1 escape from latency, in the presence of ART. This is followed by the elimination of reactivated, virus-producing cells. Immune modulators, including protein kinase C (PKC) activators, anti-leukemic drugs and histone deacetylase inhibitors (HDACis) have all demonstrated efficacy in the reactivation of latent virus replication. This review will focus on the potential use of these small molecules in the "shock and kill" strategy, the molecular basis for their action and the potential advantages of their immune-modulating activities.
抗逆转录病毒疗法（ART）已被证明在抑制 HIV-1 复制和疾病进展方面非常有效。然而，ART 未能从感染个体中消除病毒。HIV-1 根除的主要障碍是细胞病毒库的持续存在。因此，提出了“冲击和杀伤”策略，包括在 ART 存在的情况下诱导 HIV-1 从潜伏状态中逃逸。随后，消灭重新激活的、产生病毒的细胞。免疫调节剂，包括蛋白激酶 C（PKC）激活剂、抗白血病药物和组蛋白去乙酰化酶抑制剂（HDACi），在激活潜伏病毒复制方面均显示出疗效。本综述将重点讨论这些小分子在“冲击和杀伤”策略中的潜在用途、它们作用的分子基础以及其免疫调节活性的潜在优势。
