JCI Insight. 2017 Jan 12;2(1):e85811. doi: 10.1172/jci.insight.85811.
HIV-1 persistence in latent reservoirs during antiretroviral therapy (ART) is the main obstacle to virus eradication. To date, there is no marker that adequately identifies latently infected CD4 T cells in vivo. Using a well-established ex vivo model, we generated latently infected CD4 T cells and identified interferon-induced transmembrane protein 1 (IFITM1), a transmembrane antiviral factor, as being overexpressed in latently infected cells. By targeting IFITM1, we showed the efficient and specific killing of a latently infected cell line and CD4 T cells from ART-suppressed patients through antibody-dependent cytolysis. We hypothesize that IFITM1 could mark natural reservoirs, identifying an immune target for killing of latently infected cells. These novel insights could be explored to develop clinical therapeutic approaches to effectively eradicate HIV-1.
在抗逆转录病毒疗法（ART）期间，HIV-1 潜伏在储库中持续存在是病毒根除的主要障碍。迄今为止，尚无标志物能充分识别体内潜伏感染的 CD4 T 细胞。我们使用一种成熟的体外模型生成潜伏感染的 CD4 T 细胞，并鉴定出干扰素诱导跨膜蛋白 1（IFITM1），一种跨膜抗病毒因子，在潜伏感染细胞中过表达。通过靶向 IFITM1，我们通过抗体依赖性细胞裂解显示出对潜伏感染细胞系和来自接受 ART 抑制的患者的 CD4 T 细胞的有效和特异性杀伤。我们假设 IFITM1 可以标记天然储库，确定用于杀伤潜伏感染细胞的免疫靶标。可以探索这些新的见解来开发临床治疗方法，以有效根除 HIV-1。
