Centre de Recherche du CHUM, Montréal, H2X0A9, QC, Canada.
Caprion Biosciences Inc., Montréal, H2X3Y7, QC, Canada.
Nat Commun. 2019 Feb 18;10(1):814. doi: 10.1038/s41467-019-08798-7.
HIV persists in latently infected CD4 T cells during antiretroviral therapy (ART). Immune checkpoint molecules, including PD-1, are preferentially expressed at the surface of persistently infected cells. However, whether PD-1 plays a functional role in HIV latency and reservoir persistence remains unknown. Using CD4 T cells from HIV-infected individuals, we show that the engagement of PD-1 inhibits viral production at the transcriptional level and abrogates T-cell receptor (TCR)-induced HIV reactivation in latently infected cells. Conversely, PD-1 blockade with the monoclonal antibody pembrolizumab enhances HIV production in combination with the latency reversing agent bryostatin without increasing T cell activation. Our results suggest that the administration of immune checkpoint blockers to HIV-infected individuals on ART may facilitate latency disruption.
在抗逆转录病毒疗法（ART）期间，HIV 存在于潜伏感染的 CD4 T 细胞中。免疫检查点分子，包括 PD-1，优先在持续感染细胞的表面表达。然而，PD-1 是否在 HIV 潜伏和储存库持久性中发挥功能作用尚不清楚。我们使用来自 HIV 感染者的 CD4 T 细胞表明，PD-1 的结合抑制转录水平的病毒产生，并消除潜伏感染细胞中 T 细胞受体（TCR）诱导的 HIV 再激活。相反，用单克隆抗体 pembrolizumab 阻断 PD-1 与潜伏逆转剂 bryostatin 联合使用可增强 HIV 的产生，而不会增加 T 细胞的激活。我们的研究结果表明，在接受 ART 的 HIV 感染者中使用免疫检查点抑制剂可能有助于打破潜伏。
