Centre for Virus Research, Westmead Institute for Medical Research, Sydney, NSW, Australia.
Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
Front Immunol. 2018 Oct 15;9:2339. doi: 10.3389/fimmu.2018.02339. eCollection 2018.
The advent of antiretroviral therapy (ART) has seen a dramatic decrease in the morbidity and mortality of individuals infected with human immunodeficiency virus (HIV). However, ART is not curative and HIV persists in treated individuals within a pool of infected CD4 memory T cells. The targeting and elimination of these cells, termed the latent HIV reservoir, may be essential in establishing a cure for HIV. Current HIV reservoir research is focused on identifying cells that harbor latent, replication-competent, HIV provirus using specific cell surface markers. Recently, studies have turned to immune checkpoint (IC) molecules, such as programmed cell death protein 1 (PD-1). IC molecules are regulators of the immune system and have previously been linked to HIV infection. Furthermore, cells isolated from treated individuals co-expressing PD-1 alongside other IC molecules are enriched for HIV DNA. Administration of a IC blocking antibodies resulted in an increase of cell-associated HIV RNA within an individual, indicating the potential for this therapeutic to be utilized as a latency reversing agent. IC inhibitors could target CD4 T cells expressing IC molecules and possibly enhance HIV transcription, allowing for the elimination of these cells by either ART or the immune system. However, treatment with IC inhibitors has been associated with toxicities such as immune-related adverse events and therefore future studies should proceed with caution.
抗逆转录病毒疗法（ART）的出现显著降低了感染人类免疫缺陷病毒（HIV）个体的发病率和死亡率。然而，ART 并不能治愈 HIV，HIV 仍然存在于治疗个体的感染 CD4 记忆 T 细胞池中。靶向和消除这些细胞，即潜伏 HIV 储库，可能是建立 HIV 治愈方法的关键。目前的 HIV 储库研究集中在使用特定的细胞表面标志物来识别携带潜伏、复制能力的 HIV 前病毒的细胞。最近，研究转向了免疫检查点（IC）分子，如程序性细胞死亡蛋白 1（PD-1）。IC 分子是免疫系统的调节剂，先前与 HIV 感染有关。此外，从接受治疗的个体中分离出的同时表达 PD-1 和其他 IC 分子的细胞富含 HIV DNA。IC 阻断抗体的给药导致个体中细胞相关 HIV RNA 的增加，表明该治疗方法有潜力作为潜伏逆转剂。IC 抑制剂可以靶向表达 IC 分子的 CD4 T 细胞，并可能增强 HIV 转录，从而通过 ART 或免疫系统消除这些细胞。然而，IC 抑制剂的治疗与免疫相关不良事件等毒性有关，因此未来的研究应谨慎进行。
