The persistence of CD4⁺ T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics to enhance HIV-1-specific immune responses and clear infected cells will probably be necessary to achieve reduction of the latent reservoir. In the present study, we report two single-chain diabodies (scDbs) that target the HIV-1 envelope protein (Env) and the human type III Fcγ receptor (CD16). We show that the scDbs promoted robust and HIV-1-specific natural killer (NK) cell activation and NK cell-mediated lysis of infected cells. Cocultures of CD4⁺ T cells from people with HIV-1 on antiretroviral therapy (ART) with autologous NK cells and the scDbs resulted in marked elimination of reservoir cells that was dependent on latency reversal. Treatment of human interleukin-15 transgenic NSG mice with one of the scDbs after ART initiation enhanced NK cell activity and reduced reservoir size. Thus, HIV-1-specific scDbs merit further evaluation as potential therapeutics for clearance of the latent reservoir.

^{携带潜伏人类免疫缺陷病毒-1 (HIV-1) 原病毒的 CD4 +} T 细胞的持续存在是治愈的主要障碍。为了减少潜伏病毒库，可能需要新的疗法来增强 HIV-1 特异性免疫反应并清除受感染的细胞。在本研究中，我们报道了两种针对 HIV-1 包膜蛋白 (Env) 和人 III 型 Fcγ 受体 (CD16) 的单链双抗体 (scDbs)。我们发现 scDb 促进了 HIV-1 特异性自然杀伤 (NK) 细胞的强劲激活和 NK 细胞介导的感染细胞裂解。将接受抗逆转录病毒治疗 (ART) 的 HIV-1 患者的CD4 ⁺ T 细胞与自体 NK 细胞和 scDb 共培养，可显着消除依赖于潜伏期逆转的储存细胞。ART 开始后，用一种 scDb 治疗人白细胞介素 15 转基因 NSG 小鼠可增强 NK 细胞活性并减小储库大小。因此，HIV-1特异性scDb值得进一步评估作为清除潜伏病毒库的潜在疗法。